Trial Outcomes & Findings for Impact on Carriage, Acute Otitis Media, Immuno & Safety of GSK Biologicals' Pneumococcal Conjugate Vaccine 1024850A (NCT NCT00839254)

Last Updated: 2020-12-17

Results Overview

The PYAR (Person-Year Rate) as regards subjects with culture-confirmed invasive pneumococcal disease (IPD) due to any of the pneumococcal vaccine serotypes was tabulated (vaccine pneumococcal serotypes = serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F). PYAR was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

6181 participants

Primary outcome timeframe

Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months).

Results posted on

2020-12-17

Participant Flow

This study is linked with 10PN-PD-DIT-043 (111442) study (NCT00861380.-EudraCT: 2008-005149-48) with which primary objectives and outcomes are common. Subjects of 10PN-PD-DIT-043 study contributed to the results of this study.

Out of 6183 subjects enrolled, 6177 were analyzed:(6174 subjects and 3 of them received 2 subject numbers, without any impact on the results of the analyses. Total population assessed for combined analyses performed on both studies included 45977 subjects, see details in groups description.

Participant milestones

Participant milestones
Measure	10Pn3+1-6W-6M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.	10Pn2+1-6W-6M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.	Ctrl3+1-6W-6M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.	Ctrl2+1-6W-6M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.	10Pn7-11M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.	Ctrl7-11M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.	10Pn12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Overall Study STARTED	1849	1316	1069	859	241	204	368	271
Overall Study COMPLETED	1696	1224	979	797	204	178	340	256
Overall Study NOT COMPLETED	153	92	90	62	37	26	28	15

Reasons for withdrawal

Reasons for withdrawal
Measure	10Pn3+1-6W-6M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.	10Pn2+1-6W-6M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.	Ctrl3+1-6W-6M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.	Ctrl2+1-6W-6M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.	10Pn7-11M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.	Ctrl7-11M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.	10Pn12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Overall Study Protocol Violation	0	1	1	1	0	0	1	2
Overall Study Physician Decision	0	1	0	0	0	0	0	1
Overall Study Wrong treatment number allocation	0	1	0	0	0	1	0	0
Overall Study Adverse Event	12	6	3	5	2	1	0	1
Overall Study Withdrawal by Subject	87	53	54	32	27	15	22	9
Overall Study Wrong group allocation	0	0	0	0	0	0	1	0
Overall Study Parents wanted pneumococcal vaccine	1	0	0	0	0	1	0	0
Overall Study Withdrawn due to non-compliance	2	0	0	0	0	0	0	0
Overall Study Lost to Follow-up	51	30	32	24	8	8	4	2

Baseline Characteristics

Impact on Carriage, Acute Otitis Media, Immuno & Safety of GSK Biologicals' Pneumococcal Conjugate Vaccine 1024850A

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	10Pn3+1-6W-6M/053 Group n=1849 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.	10Pn2+1-6W-6M/053 Group n=1316 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.	Ctrl3+1-6W-6M/053 Group n=1069 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.	Ctrl2+1-6W-6M/053 Group n=859 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.	10Pn7-11M/053 Group n=241 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.	Ctrl7-11M/053 Group n=204 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.	10Pn12-18M/053 Group n=368 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.	Ctrl12-18M/053 Group n=271 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.	Total n=6177 Participants Total of all reporting groups
Race/Ethnicity, Customized Unspecified	19 Participants n=5 Participants	8 Participants n=7 Participants	7 Participants n=5 Participants	8 Participants n=4 Participants	2 Participants n=21 Participants	2 Participants n=10 Participants	2 Participants n=115 Participants	1 Participants n=24 Participants	49 Participants n=42 Participants
Age, Continuous	2.4 Months STANDARD_DEVIATION 1.02 • n=5 Participants	2.3 Months STANDARD_DEVIATION 0.95 • n=7 Participants	2.6 Months STANDARD_DEVIATION 1.19 • n=5 Participants	2.4 Months STANDARD_DEVIATION 1 • n=4 Participants	9 Months STANDARD_DEVIATION 1.44 • n=21 Participants	8.7 Months STANDARD_DEVIATION 1.39 • n=10 Participants	15 Months STANDARD_DEVIATION 1.99 • n=115 Participants	15.2 Months STANDARD_DEVIATION 1.99 • n=24 Participants	7.2 Months STANDARD_DEVIATION 1.37 • n=42 Participants
Sex: Female, Male Female	921 Participants n=5 Participants	681 Participants n=7 Participants	551 Participants n=5 Participants	393 Participants n=4 Participants	118 Participants n=21 Participants	113 Participants n=10 Participants	173 Participants n=115 Participants	142 Participants n=24 Participants	3092 Participants n=42 Participants
Sex: Female, Male Male	928 Participants n=5 Participants	635 Participants n=7 Participants	518 Participants n=5 Participants	466 Participants n=4 Participants	123 Participants n=21 Participants	91 Participants n=10 Participants	195 Participants n=115 Participants	129 Participants n=24 Participants	3085 Participants n=42 Participants
Race/Ethnicity, Customized African heritage / African American	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=10 Participants	2 Participants n=115 Participants	0 Participants n=24 Participants	5 Participants n=42 Participants
Race/Ethnicity, Customized White - Arabic / north African heritage	7 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	6 Participants n=4 Participants	3 Participants n=21 Participants	0 Participants n=10 Participants	2 Participants n=115 Participants	0 Participants n=24 Participants	27 Participants n=42 Participants
Race/Ethnicity, Customized White - Caucasian / European heritage	1822 Participants n=5 Participants	1303 Participants n=7 Participants	1058 Participants n=5 Participants	845 Participants n=4 Participants	235 Participants n=21 Participants	201 Participants n=10 Participants	362 Participants n=115 Participants	270 Participants n=24 Participants	6096 Participants n=42 Participants

PRIMARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months).

Population: The analysis was performed on the Infant Vaccinated cohort, including all vaccinated, subjects in the 10PN-PD-DIT-043 NCT00839254 study and vaccinated subjects of 10PN-PD-DIT-053 NCT00839254 study contributing to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 3-dose primary vaccination course.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=10273 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=10201 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate as Regards Subjects With Culture-confirmed IPD Due to Any of the 10 Pneumococcal Vaccine Serotypes. In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course.	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.564 Participants per 1000 person-years Interval 0.291 to 0.984	—	—	—	—	—	—

PRIMARY outcome

Population: The analysis was performed on the Infant Vaccinated cohort, which included all vaccinated subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 2-dose primary vaccination course.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=10054 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=10201 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate as Regards Subjects With Culture-confirmed IPD Due to Any of the 10 Pneumococcal Vaccine Serotypes. In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course.	0.048 Participants per 1000 person-years Interval 0.001 to 0.27	0.564 Participants per 1000 person-years Interval 0.291 to 0.984	—	—	—	—	—	—

SECONDARY outcome

Population: The analysis was performed on the Infant Vaccinated cohort, which included all vaccinated,subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 3-dose primary vaccination course.

The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=10273 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=10201 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Culture confirmed ID	0.093 Participants per 1000 person-years Interval 0.011 to 0.336	0.845 Participants per 1000 person-years Interval 0.501 to 1.336	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Pneumococcal invasive disease (IPD)	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.657 Participants per 1000 person-years Interval 0.359 to 1.103	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Serotype 4	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.000 Participants per 1000 person-years Interval 0.0 to 0.173	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Serotype 6B	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.235 Participants per 1000 person-years Interval 0.076 to 0.548	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Serotype 7F	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.000 Participants per 1000 person-years Interval 0.0 to 0.173	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Serotype 14	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.188 Participants per 1000 person-years Interval 0.051 to 0.481	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Serotype 18C	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Serotype 19F	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Serotype 23F	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Cross-reactive serotypes	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.094 Participants per 1000 person-years Interval 0.011 to 0.339	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Serotype 6A	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Serotype 19A	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Other pneumococcal serotypes	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.000 Participants per 1000 person-years Interval 0.0 to 0.173	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Serotype 3	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.000 Participants per 1000 person-years Interval 0.0 to 0.173	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Serotype 15C	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.000 Participants per 1000 person-years Interval 0.0 to 0.173	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. H. influenzae ID	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Non-typeable (NTHI)	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Other bacteria	0.093 Participants per 1000 person-years Interval 0.011 to 0.336	0.188 Participants per 1000 person-years Interval 0.051 to 0.481	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Neisseria meningitidis	0.093 Participants per 1000 person-years Interval 0.011 to 0.336	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Streptococcus pyogenes	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.094 Participants per 1000 person-years Interval 0.011 to 0.339	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Moraxella catarrhalis	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—

SECONDARY outcome

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=10054 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=10201 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Culture confirmed ID	0.194 Participants per 1000 person-years Interval 0.053 to 0.496	0.845 Participants per 1000 person-years Interval 0.501 to 1.336	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Pneumococcal invasive disease (IPD)	0.097 Participants per 1000 person-years Interval 0.012 to 0.35	0.657 Participants per 1000 person-years Interval 0.359 to 1.103	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Vaccine serotypes (vaccine type-IPD)	0.048 Participants per 1000 person-years Interval 0.001 to 0.27	0.564 Participants per 1000 person-years Interval 0.291 to 0.984	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Serotype 4	0.000 Participants per 1000 person-years Interval 0.0 to 0.179	0.000 Participants per 1000 person-years Interval 0.0 to 0.173	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Serotype 6B	0.000 Participants per 1000 person-years Interval 0.0 to 0.179	0.235 Participants per 1000 person-years Interval 0.076 to 0.548	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Serotype 7F	0.048 Participants per 1000 person-years Interval 0.001 to 0.27	0.000 Participants per 1000 person-years Interval 0.0 to 0.173	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Serotype 14	0.000 Participants per 1000 person-years Interval 0.0 to 0.179	0.188 Participants per 1000 person-years Interval 0.051 to 0.481	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Serotype 18C	0.000 Participants per 1000 person-years Interval 0.0 to 0.179	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Serotype 19F	0.000 Participants per 1000 person-years Interval 0.0 to 0.179	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Serotype 23F	0.000 Participants per 1000 person-years Interval 0.0 to 0.179	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Cross-reactive serotypes	0.000 Participants per 1000 person-years Interval 0.0 to 0.179	0.094 Participants per 1000 person-years Interval 0.011 to 0.339	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Serotype 6A	0.000 Participants per 1000 person-years Interval 0.0 to 0.179	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Serotype 19A	0.000 Participants per 1000 person-years Interval 0.0 to 0.179	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Other pneumococcal serotypes	0.048 Participants per 1000 person-years Interval 0.001 to 0.27	0.000 Participants per 1000 person-years Interval 0.0 to 0.173	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Serotype 3	0.048 Participants per 1000 person-years Interval 0.001 to 0.27	0.000 Participants per 1000 person-years Interval 0.0 to 0.173	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Serotype 15C	0.000 Participants per 1000 person-years Interval 0.0 to 0.179	0.000 Participants per 1000 person-years Interval 0.0 to 0.173	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. H. influenzae ID	0.048 Participants per 1000 person-years Interval 0.001 to 0.27	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Non-typeable (NTHI)	0.048 Participants per 1000 person-years Interval 0.001 to 0.27	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Other bacteria	0.048 Participants per 1000 person-years Interval 0.001 to 0.27	0.188 Participants per 1000 person-years Interval 0.051 to 0.481	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Neisseria meningitidis	0.048 Participants per 1000 person-years Interval 0.001 to 0.27	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Streptococcus pyogenes	0.000 Participants per 1000 person-years Interval 0.0 to 0.179	0.094 Participants per 1000 person-years Interval 0.011 to 0.339	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Moraxella catarrhalis	0.000 Participants per 1000 person-years Interval 0.0 to 0.179	0.047 Participants per 1000 person-years Interval 0.001 to 0.262	—	—	—	—	—	—

SECONDARY outcome

Population: The analysis was performed on the Catch-up Vaccinated cohort, which included all vaccinated subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with a 2-dose primary vaccination between 7 and 11 months of age.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=3880 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=1908 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Serotype 19A	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.000 Participants per 1000 person-years Interval 0.0 to 0.823	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Other pneumococcal serotypes	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.000 Participants per 1000 person-years Interval 0.0 to 0.823	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Culture confirmed ID	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.446 Participants per 1000 person-years Interval 0.054 to 1.612	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Pneumococcal invasive disease (IPD)	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.446 Participants per 1000 person-years Interval 0.054 to 1.612	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Vaccine serotypes (vaccine type-IPD)	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.446 Participants per 1000 person-years Interval 0.054 to 1.612	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Serotype 4	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.000 Participants per 1000 person-years Interval 0.0 to 0.823	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Serotype 6B	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.000 Participants per 1000 person-years Interval 0.0 to 0.823	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Serotype 7F	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.223 Participants per 1000 person-years Interval 0.006 to 1.243	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Serotype 14	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.223 Participants per 1000 person-years Interval 0.006 to 1.243	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Serotype 18C	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.000 Participants per 1000 person-years Interval 0.0 to 0.823	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Serotype 19F	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.000 Participants per 1000 person-years Interval 0.0 to 0.823	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Serotype 23F	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.000 Participants per 1000 person-years Interval 0.0 to 0.823	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Cross-reactive serotypes	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.000 Participants per 1000 person-years Interval 0.0 to 0.823	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Serotype 6A	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.000 Participants per 1000 person-years Interval 0.0 to 0.823	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Serotype 3	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.000 Participants per 1000 person-years Interval 0.0 to 0.823	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Serotype 15C	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.000 Participants per 1000 person-years Interval 0.0 to 0.823	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. H. influenzae ID	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.000 Participants per 1000 person-years Interval 0.0 to 0.823	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Non-typeable (NTHI)	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.000 Participants per 1000 person-years Interval 0.0 to 0.823	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Other bacteria	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.000 Participants per 1000 person-years Interval 0.0 to 0.823	—	—	—	—	—	—

SECONDARY outcome

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=6535 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=3126 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Culture confirmed ID	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.674 Participants per 1000 person-years Interval 0.219 to 1.572	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Pneumococcal invasive disease (IPD)	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.674 Participants per 1000 person-years Interval 0.219 to 1.572	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Vaccine serotypes (vaccine type-IPD)	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.404 Participants per 1000 person-years Interval 0.083 to 1.181	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Serotype 4	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.135 Participants per 1000 person-years Interval 0.003 to 0.751	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Serotype 6B	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.135 Participants per 1000 person-years Interval 0.003 to 0.751	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Serotype 7F	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.000 Participants per 1000 person-years Interval 0.0 to 0.497	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Serotype 14	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.000 Participants per 1000 person-years Interval 0.0 to 0.497	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Serotype 18C	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.000 Participants per 1000 person-years Interval 0.0 to 0.497	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Serotype 19F	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.135 Participants per 1000 person-years Interval 0.003 to 0.751	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Serotype 23F	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.000 Participants per 1000 person-years Interval 0.0 to 0.497	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Cross-reactive serotypes	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.000 Participants per 1000 person-years Interval 0.0 to 0.497	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Serotype 6A	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.000 Participants per 1000 person-years Interval 0.0 to 0.497	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Serotype 19A	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.000 Participants per 1000 person-years Interval 0.0 to 0.497	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Other pneumococcal serotypes	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.269 Participants per 1000 person-years Interval 0.033 to 0.974	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Serotype 3	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.135 Participants per 1000 person-years Interval 0.003 to 0.751	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Serotype 15C	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.135 Participants per 1000 person-years Interval 0.003 to 0.751	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. H. influenzae ID	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.000 Participants per 1000 person-years Interval 0.0 to 0.497	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Non-typeable (NTHI)	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.000 Participants per 1000 person-years Interval 0.0 to 0.497	—	—	—	—	—	—
Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Other bacteria	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.000 Participants per 1000 person-years Interval 0.0 to 0.497	—	—	—	—	—	—

SECONDARY outcome

The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a probable or culture confirmed ID) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=10273 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=10201 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in the Prevention of Probable Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Probable cases of IPD	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.141 Participants per 1000 person-years Interval 0.029 to 0.412	—	—	—	—	—	—
Person Year Rate in the Prevention of Probable Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Confirmed or probable cases of IPD	0.000 Participants per 1000 person-years Interval 0.0 to 0.172	0.798 Participants per 1000 person-years Interval 0.465 to 1.278	—	—	—	—	—	—

SECONDARY outcome

Population: The analysis was performed on the Infant Vaccinated cohort, all vaccinated subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 2-dose primary vaccination course.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=10054 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=10201 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in the Prevention of Probable or Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Probable cases of IPD	0.000 Participants per 1000 person-years Interval 0.0 to 0.179	0.141 Participants per 1000 person-years Interval 0.029 to 0.412	—	—	—	—	—	—
Person Year Rate in the Prevention of Probable or Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Confirmed or probable cases of IPD	0.097 Participants per 1000 person-years Interval 0.012 to 0.35	0.798 Participants per 1000 person-years Interval 0.465 to 1.278	—	—	—	—	—	—

SECONDARY outcome

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=3880 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=1908 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in the Prevention of Probable or Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Probable cases of IPD	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.000 Participants per 1000 person-years Interval 0.0 to 0.823	—	—	—	—	—	—
Person Year Rate in the Prevention of Probable or Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule. Confirmed or probable cases of IPD	0.000 Participants per 1000 person-years Interval 0.0 to 0.41	0.446 Participants per 1000 person-years Interval 0.054 to 1.612	—	—	—	—	—	—

SECONDARY outcome

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=6535 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=3126 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in the Prevention of Probable or Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Probable cases of IPD	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.000 Participants per 1000 person-years Interval 0.0 to 0.497	—	—	—	—	—	—
Person Year Rate in the Prevention of Probable or Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule. Confirmed or probable cases of IPD	0.000 Participants per 1000 person-years Interval 0.0 to 0.24	0.674 Participants per 1000 person-years Interval 0.219 to 1.572	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months.

PYAR was calculated: n (= number of subjects with hospital-diagnosed pneumonia) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. Hospital-diagnosed pneumonia (HDP) cases identified based on hospital discharge diagnosis using international Classification of Disease (ICD)-10 diagnosis codes: J10.0 (Influenza with HDP, other influenza virus identified), J11.0 (Influenza with HDP, virus not identified), J12 (Viral HDP, not elsewhere classified), J13 (HDP due to Sp.), J14 (for HDP due to Hi.), J15 (all HDP, not elsewhere classified), J16 (HDP due to other infectious organisms, not elsewhere classified), J17 (HDP in diseases classified elsewhere), J18 (HDP organism unspecified), J85.1 (Abscess of lung with HDP), and J86 (Pyothorax including empyema).

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=10273 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=10200 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in Reducing Hospital-diagnosed Pneumonia- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course.	10.131 Participants per 1000 person-years Interval 8.804 to 11.601	13.854 Participants per 1000 person-years Interval 12.287 to 15.566	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=10054 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=10200 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in Reducing Hospital-diagnosed Pneumonia - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course.	10.155 Participants per 1000 person-years Interval 8.8 to 11.66	13.854 Participants per 1000 person-years Interval 12.287 to 15.566	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=3880 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=1907 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in Reducing Hospital-diagnosed Pneumonia- In Children Starting Vaccination in the 7-11 Months Schedule.	10.263 Participants per 1000 person-years Interval 8.242 to 12.63	15.752 Participants per 1000 person-years Interval 12.232 to 19.97	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=6534 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=3126 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in Reducing Hospital-diagnosed Pneumonia - In Children Starting Vaccination in the 12-18 Months Schedule.	9.322 Participants per 1000 person-years Interval 7.832 to 11.013	11.739 Participants per 1000 person-years Interval 9.363 to 14.533	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months.

PYAR was calculated: n (= number of subjects with hospital-diagnosed pneumonia \[HDP\]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata for non-consolidated HDP and without strata for consolidated HDP). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. CXR HDP was defined as a HDP case with the presence of abnormal pulmonary infiltrates on the CXR as per independent review panel judgement using WHO methodology. Abnormal pulmonary infiltrates could be either with (Consolidated HDP) or without (Non-consolidated HDP) alveolar consolidation/pleural effusion. New cases of HDP and CXR HDP were based on a 30-day rule, i.e. a new episode was considered if at least a 30-day interval elapsed from the onset of the previous episode.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=10273 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=10200 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in Reducing Hospital-diagnosed Pneumonia With Chest X-ray (CXR) Reading According to WHO Criteria- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Consolidated pneumonia	2.181 Participants per 1000 person-years Interval 1.591 to 2.919	3.965 Participants per 1000 person-years Interval 3.149 to 4.929	—	—	—	—	—	—
Person Year Rate in Reducing Hospital-diagnosed Pneumonia With Chest X-ray (CXR) Reading According to WHO Criteria- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Non-consolidated pneumonia	2.908 Participants per 1000 person-years Interval 2.219 to 3.744	2.937 Participants per 1000 person-years Interval 2.241 to 3.781	—	—	—	—	—	—
Person Year Rate in Reducing Hospital-diagnosed Pneumonia With Chest X-ray (CXR) Reading According to WHO Criteria- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Consolidated or non-consolidated pneumonia	5.090 Participants per 1000 person-years Interval 4.163 to 6.161	6.903 Participants per 1000 person-years Interval 5.81 to 8.141	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=10054 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=10200 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in Reducing Hospital-diagnosed Pneumonia With CXR Reading According to WHO Criteria - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Consolidated pneumonia	2.273 Participants per 1000 person-years Interval 1.658 to 3.042	3.965 Participants per 1000 person-years Interval 3.149 to 4.929	—	—	—	—	—	—
Person Year Rate in Reducing Hospital-diagnosed Pneumonia With CXR Reading According to WHO Criteria - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Non-consolidated pneumonia	2.627 Participants per 1000 person-years Interval 1.962 to 3.445	2.937 Participants per 1000 person-years Interval 2.241 to 3.781	—	—	—	—	—	—
Person Year Rate in Reducing Hospital-diagnosed Pneumonia With CXR Reading According to WHO Criteria - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Consolidated or non-consolidated pneumonia	4.901 Participants per 1000 person-years Interval 3.974 to 5.978	6.903 Participants per 1000 person-years Interval 5.81 to 8.141	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months.

Population: The analysis was performed on the Catch-up Vaccinated cohort, which included all vaccinated,subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with a 2-dose primary vaccination between 7 and 11 months of age.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=3880 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=1907 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in Reducing Hospital-diagnosed Pneumonia With CXR Reading According to WHO Criteria - In Children Starting Vaccination in the 7-11 Months Schedule. Consolidated pneumonia	1.960 Participants per 1000 person-years Interval 1.142 to 3.139	4.401 Participants per 1000 person-years Interval 2.65 to 6.873	—	—	—	—	—	—
Person Year Rate in Reducing Hospital-diagnosed Pneumonia With CXR Reading According to WHO Criteria - In Children Starting Vaccination in the 7-11 Months Schedule. Non-consolidated pneumonia	3.344 Participants per 1000 person-years Interval 2.24 to 4.803	4.865 Participants per 1000 person-years Interval 3.011 to 7.436	—	—	—	—	—	—
Person Year Rate in Reducing Hospital-diagnosed Pneumonia With CXR Reading According to WHO Criteria - In Children Starting Vaccination in the 7-11 Months Schedule. Consolidated or non-consolidated pneumonia	5.305 Participants per 1000 person-years Interval 3.884 to 7.076	9.266 Participants per 1000 person-years Interval 6.62 to 12.618	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=6534 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=3126 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in Reducing Hospital-diagnosed Pneumonia With CXR Reading According to WHO Criteria - In Children Starting Vaccination in the 12-18 Months Schedule. Consolidated pneumonia	1.824 Participants per 1000 person-years Interval 1.202 to 2.654	3.494 Participants per 1000 person-years Interval 2.261 to 5.157	—	—	—	—	—	—
Person Year Rate in Reducing Hospital-diagnosed Pneumonia With CXR Reading According to WHO Criteria - In Children Starting Vaccination in the 12-18 Months Schedule. Non-consolidated pneumonia	2.837 Participants per 1000 person-years Interval 2.045 to 3.835	2.935 Participants per 1000 person-years Interval 1.817 to 4.486	—	—	—	—	—	—
Person Year Rate in Reducing Hospital-diagnosed Pneumonia With CXR Reading According to WHO Criteria - In Children Starting Vaccination in the 12-18 Months Schedule. Consolidated or non-consolidated pneumonia	4.661 Participants per 1000 person-years Interval 3.626 to 5.899	6.428 Participants per 1000 person-years Interval 4.706 to 8.574	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months.

PYAR was calculated: n (= number of subjects with tympanostomy tube placement\[TTP\]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. A TTP episode was defined as a TTP episode classified under the DCA 20 code in the Finnish National Institute of Health and Welfare (THL) and Social Insurance Institution of Finland (KELA) registers, using the Nordic Centre for Classifications in Health Care (NOMESCO) Classification of Surgical Procedures (NCSP), version 1.12 from January 2008, and could refer to either an unilateral or a bilateral TTP procedure. New episodes of TTP defined according to a 30-day rule meaning that a new episode was considered if at least 30-day interval elapsed from the onset of the previous episode.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=10273 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=10200 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in Prevention of All Tympanostomy Tube Placements- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course.	68.735 Participants per 1000 person-years Interval 65.203 to 72.408	79.504 Participants per 1000 person-years Interval 75.683 to 83.467	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=10054 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=10200 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in Prevention of All Tympanostomy Tube Placements - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course.	66.083 Participants per 1000 person-years Interval 62.55 to 69.764	79.504 Participants per 1000 person-years Interval 75.683 to 83.467	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=3880 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=1907 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in Prevention of All Tympanostomy Tube Placements - In Children Starting Vaccination in the 7-11 Months Schedule.	68.153 Participants per 1000 person-years Interval 62.769 to 73.876	79.920 Participants per 1000 person-years Interval 71.708 to 88.814	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=6534 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=3126 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in Prevention of All Tympanostomy Tube Placements - In Children Starting Vaccination in the 12-18 Months Schedule.	56.809 Participants per 1000 person-years Interval 53.034 to 60.782	58.973 Participants per 1000 person-years Interval 53.48 to 64.877	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months.

PYAR was calculated: n (= number of subjects with antimicrobial prescriptions (APs)) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. An APs episode was an episode of APs to an infant/child falling under following Anatomic Therapeutic Chemical \[ATC\] codes: J01 (APs) and following codes for AP usually recommended for otitis media (OM) and respiratory tract infections (RTI). "For OM and RTI" category corresponds to following definition: APs for antibacterial usually recommended for OM and RTI (ATC codes: J01CA04, J01CR02, J01CE02, J01DC02, J01DC04, J01EE02, J01FA09 and J01FA10). New episodes of APs were analyzed according to a 2-day rule meaning new episode considered if at least 2 day interval elapsed from the onset of the previous episode.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=10273 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=10200 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in Prevention of All Antimicrobial Prescriptions- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. Antimicrobial prescriptions (ATC code J01)	1592.585 Participants per 1000 person-years Interval 1575.411 to 1609.901	1706.194 Participants per 1000 person-years Interval 1688.328 to 1724.202	—	—	—	—	—	—
Person Year Rate in Prevention of All Antimicrobial Prescriptions- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course. For otitis media and respiratory infections	1451.141 Participants per 1000 person-years Interval 1434.749 to 1467.674	1565.692 Participants per 1000 person-years Interval 1548.579 to 1582.947	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=10054 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=10200 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in Prevention of All Antimicrobial Prescriptions - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. Antimicrobial prescriptions (ATC code J01)	1552.493 Participants per 1000 person-years Interval 1535.183 to 1569.95	1706.194 Participants per 1000 person-years Interval 1688.328 to 1724.202	—	—	—	—	—	—
Person Year Rate in Prevention of All Antimicrobial Prescriptions - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course. For otitis media and respiratory infections	1415.983 Participants per 1000 person-years Interval 1399.453 to 1432.659	1565.692 Participants per 1000 person-years Interval 1548.579 to 1582.947	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=3880 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=1907 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in Prevention of All Antimicrobial Prescriptions - In Children Starting Vaccination in the 7-11 Months Schedule. Antimicrobial prescriptions (ATC code J01)	1536.618 Participants per 1000 person-years Interval 1510.637 to 1562.934	1649.360 Participants per 1000 person-years Interval 1611.269 to 1688.124	—	—	—	—	—	—
Person Year Rate in Prevention of All Antimicrobial Prescriptions - In Children Starting Vaccination in the 7-11 Months Schedule. For otitis media and respiratory infections	1390.856 Participants per 1000 person-years Interval 1366.143 to 1415.903	1499.713 Participants per 1000 person-years Interval 1463.401 to 1536.698	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=6534 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=3126 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Person Year Rate in Prevention of All Antimicrobial Prescriptions - In Children Starting Vaccination in the 12-18 Months Schedule. Antimicrobial prescriptions (ATC code J01)	1315.936 Participants per 1000 person-years Interval 1297.521 to 1334.547	1421.774 Participants per 1000 person-years Interval 1394.28 to 1449.675	—	—	—	—	—	—
Person Year Rate in Prevention of All Antimicrobial Prescriptions - In Children Starting Vaccination in the 12-18 Months Schedule. For otitis media and respiratory infections	1177.729 Participants per 1000 person-years Interval 1160.312 to 1195.343	1271.268 Participants per 1000 person-years Interval 1245.277 to 1297.665	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - mean FU time=24 months.

Antimicrobial susceptibility classification of IPD isolates reported during IPD follow-up with percentages for each serotype for the following categories: S= susceptible; I = intermediate ; R = resistant; N = not available.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=2 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=24 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-4 -Pencillin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-6A -Pencillin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-6B -Pencillin-I	—	0 Participants	3 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-6B -Pencillin-R	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-6B -Pencillin-S	—	0 Participants	2 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-7F -Pencillin-S	—	1 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-14 -Pencillin-I	—	0 Participants	2 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-14 -Pencillin-R	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-14 -Pencillin-S	—	0 Participants	2 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-15C -Pencillin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-18C -Pencillin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-19A -Pencillin-I	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-19F -Pencillin-I	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-19F -Pencillin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-23F -Pencillin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-N -Pencillin-N	—	1 Participants	4 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-4 -Erythromycin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-6A -Erythromycin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-6B -Erythromycin-R	—	0 Participants	5 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-6B -Erythromycin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-7F -Erythromycin-S	—	1 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-14 -Erythromycin-R	—	0 Participants	4 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-14 -Erythromycin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-15C -Erythromycin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-18C -Erythromycin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-19A -Erythromycin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-19F -Erythromycin-R	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-19F -Erythromycin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-23F -Erythromycin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-N -Erythromycin-N	—	1 Participants	4 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-4 -Tetracyclin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-6A -Tetracyclin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-6B -Tetracyclin-R	—	0 Participants	4 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-6B -Tetracyclin-S	—	0 Participants	2 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-7F -Tetracyclin-S	—	1 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-14 -Tetracyclin-S	—	0 Participants	5 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-15C -Tetracyclin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-18C -Tetracyclin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-19A -Tetracyclin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-19F -Tetracyclin-R	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-19F -Tetracyclin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-23F -Tetracyclin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-N -Tetracyclin-N	—	1 Participants	4 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-4 -Levoffloxacin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-6A -Levoffloxacin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-6B -Levoffloxacin-S	—	0 Participants	6 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-7F -Levoffloxacin-S	—	1 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-14 -Levoffloxacin-S	—	0 Participants	5 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-15C -Levoffloxacin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-18C -Levoffloxacin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-19A -Levoffloxacin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-7F -Ceftriaxone-S	—	1 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-14 -Ceftriaxone-I	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-14 -Ceftriaxone-S	—	0 Participants	4 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-15C -Ceftriaxone-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-18C -Ceftriaxone-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-19A -Ceftriaxone-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-19F -Ceftriaxone-S	—	0 Participants	2 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-23F -Ceftriaxone-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-N -Ceftriaxone-N	—	1 Participants	4 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-4 -Clindamycin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-6A -Clindamycin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-6B -Clindamycin-R	—	0 Participants	4 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-6B -Clindamycin-S	—	0 Participants	2 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-7F -Clindamycin-S	—	1 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-14 -Clindamycin-N	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-14 -Clindamycin-S	—	0 Participants	4 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-15C -Clindamycin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-18C -Clindamycin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-19A -Clindamycin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-19F -Clindamycin-R	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-19F -Clindamycin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-23F -Clindamycin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-N -Clindamycin-N	—	1 Participants	4 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-19F -Levoffloxacin-S	—	0 Participants	2 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-23F -Levoffloxacin-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-N -Levoffloxacin-N	—	1 Participants	4 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-4 -Ceftriaxone-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-6A -Ceftriaxone-S	—	0 Participants	1 Participants	—	—	—	—	—
Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course Serotype-6B -Ceftriaxone-S	—	0 Participants	6 Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: From the administration of the first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (at least 30 months).

Population: The analysis was performed in a subset of vaccinated subjects including all vaccinated subjects enrolled in the 10PNPD-DIT-053 study in the Turku area and those vaccinated subjects enrolled in the 10PN-PD-DIT-043 study in the Turku area who agreed to take part in this assessment.

Analysis of this outcome was performed in the Turku area. The number of subjects reporting at least one LRTI any time after the administration of the first vaccine dose was tabulated.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=243 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=190 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=171 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group n=31 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group n=22 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group n=62 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group n=48 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Number of Subjects With Lower Respiratory Tract Infections (LRTIs) (in a Subset of Subjects in Turku Area )	19 Participants	19 Participants	19 Participants	3 Participants	1 Participants	5 Participants	2 Participants	—

SECONDARY outcome

Timeframe: From the administration of the first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (at least 30 months).

Analysis of this outcome was performed in the Turku area. The number of subjects reporting at least one URTI any time after the administration of the first vaccine dose was tabulated.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=243 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=190 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=171 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group n=31 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group n=22 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group n=62 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group n=48 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Number of Subjects With Upper Respiratory Tract Infections (URTIs) (in a Subset of Subjects in Turku Area )	158 Participants	124 Participants	94 Participants	14 Participants	15 Participants	27 Participants	19 Participants	—

SECONDARY outcome

Timeframe: Within 4 days (4D) after each vaccination (M0+4D, M1+4D [only for 3+1 schedule], M2+4D, M8+4D [booster dose] for 6W-6M subjects; M0+4D, M2+4D, M6+4D [booster dose] for 7M-11M subjects; M0+4D, M6+4D for 12M-18M subjects)

Population: The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented.

Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=1846 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=1302 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=1066 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group n=852 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group n=237 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group n=202 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group n=363 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group n=270 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Any Pain, Dose 1	807 Participants	611 Participants	146 Participants	106 Participants	120 Participants	33 Participants	220 Participants	65 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Grade 3 Pain, Dose 1	60 Participants	43 Participants	2 Participants	3 Participants	6 Participants	0 Participants	19 Participants	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Any Redness (mm), Dose 1	936 Participants	675 Participants	270 Participants	214 Participants	137 Participants	48 Participants	203 Participants	93 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Grade 3 Redness (mm), Dose 1	56 Participants	48 Participants	3 Participants	0 Participants	17 Participants	0 Participants	39 Participants	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Any Swelling (mm), Dose 1	636 Participants	471 Participants	88 Participants	64 Participants	107 Participants	19 Participants	142 Participants	25 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Grade 3 Swelling (mm), Dose 1	89 Participants	69 Participants	4 Participants	1 Participants	20 Participants	9 Participants	35 Participants	1 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Any Pain, Dose 2	662 Participants	509 Participants	114 Participants	94 Participants	108 Participants	38 Participants	242 Participants	78 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Grade 3 Pain, Dose 2	23 Participants	28 Participants	2 Participants	1 Participants	11 Participants	0 Participants	45 Participants	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Any Redness (mm), Dose 2	996 Participants	690 Participants	254 Participants	203 Participants	124 Participants	57 Participants	193 Participants	85 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Grade 3 Redness (mm), Dose 2	48 Participants	63 Participants	3 Participants	0 Participants	21 Participants	0 Participants	49 Participants	1 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Any Swelling (mm), Dose 2	686 Participants	536 Participants	114 Participants	79 Participants	98 Participants	18 Participants	148 Participants	26 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Grade 3 Swelling (mm), Dose 2	67 Participants	91 Participants	4 Participants	1 Participants	19 Participants	0 Participants	34 Participants	0 Participants
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Any Pain, Dose 3	538 Participants	—	102 Participants	—	—	—	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Grade 3 Pain, Dose 3	12 Participants	—	2 Participants	—	—	—	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Any Redness (mm), Dose 3	963 Participants	—	300 Participants	—	—	—	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Grade 3 Redness (mm), Dose 3	52 Participants	—	0 Participants	—	—	—	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Any Swelling (mm), Dose 3	676 Participants	—	144 Participants	—	—	—	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Grade 3 Swelling (mm), Dose 3	62 Participants	—	1 Participants	—	—	—	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Any Pain, Booster dose	888 Participants	710 Participants	250 Participants	171 Participants	123 Participants	40 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Grade 3 Pain, Booster dose	66 Participants	41 Participants	2 Participants	2 Participants	14 Participants	2 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Any Redness (mm), Booster dose	913 Participants	702 Participants	345 Participants	238 Participants	106 Participants	54 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Grade 3 Redness (mm), Booster dose	102 Participants	103 Participants	13 Participants	2 Participants	18 Participants	0 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Any Swelling (mm), Booster dose	716 Participants	586 Participants	229 Participants	118 Participants	85 Participants	31 Participants	—	—
Number of Subjects With Any and Grade 3 Solicited Local Symptoms. Grade 3 Swelling (mm), Booster dose	102 Participants	111 Participants	10 Participants	3 Participants	14 Participants	0 Participants	—	—

SECONDARY outcome

Population: The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented.

Assessed solicited general symptoms were drowsiness, fever \[defined as rectal temperature ≥ 38 degrees Celsius (°C) or oral/axillary/tympanic temperature equal to or above 37.5°C\], irritability/fussiness and loss pf appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 fever = rectal temperature \> 40°C. Grade 3 irritability/fussiness = cried that could not be comforted/prevented normal activity. Grade 3 loss of appetite = not eating at all. Related = a symptom assessed by investigator as causally related to the vaccination.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=1846 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=1302 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=1066 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group n=852 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group n=237 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group n=202 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group n=363 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group n=270 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Any Drowsiness, Dose 3	645 Participants	—	293 Participants	—	—	—	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Any Drowsiness, Dose 1	1070 Participants	742 Participants	462 Participants	384 Participants	106 Participants	62 Participants	155 Participants	87 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Drowsiness, Dose 1	11 Participants	8 Participants	5 Participants	1 Participants	1 Participants	0 Participants	1 Participants	2 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Related Drowsiness, Dose 1	1054 Participants	738 Participants	453 Participants	374 Participants	103 Participants	57 Participants	152 Participants	81 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Any Temperature (Rectally)/(°C), Dose 1	388 Participants	289 Participants	82 Participants	78 Participants	38 Participants	16 Participants	74 Participants	28 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Temperature (Rectally)/(°C), Dose 1	2 Participants	0 Participants	1 Participants	0 Participants	8 Participants	0 Participants	2 Participants	2 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Related Temperature (Rectally)/(°C), Dose 1	381 Participants	284 Participants	78 Participants	74 Participants	35 Participants	13 Participants	69 Participants	25 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Any Irritability, Dose 1	1325 Participants	942 Participants	577 Participants	468 Participants	157 Participants	90 Participants	210 Participants	103 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Irritability, Dose 1	76 Participants	56 Participants	20 Participants	14 Participants	3 Participants	2 Participants	6 Participants	4 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Related Irritability, Dose 1	1298 Participants	937 Participants	565 Participants	460 Participants	157 Participants	83 Participants	201 Participants	96 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Any Loss of appetite, Dose 1	499 Participants	335 Participants	202 Participants	147 Participants	84 Participants	56 Participants	128 Participants	82 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Loss of appetite, Dose 1	1 Participants	3 Participants	2 Participants	0 Participants	0 Participants	1 Participants	2 Participants	4 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Related Loss of appetite, Dose 1	480 Participants	332 Participants	196 Participants	140 Participants	81 Participants	48 Participants	123 Participants	73 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Any Drowsiness, Dose 2	868 Participants	572 Participants	332 Participants	258 Participants	88 Participants	52 Participants	126 Participants	58 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Drowsiness, Dose 2	7 Participants	6 Participants	1 Participants	3 Participants	2 Participants	1 Participants	2 Participants	1 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Related Drowsiness, Dose 2	855 Participants	564 Participants	329 Participants	247 Participants	85 Participants	51 Participants	123 Participants	55 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Any Temperature (Rectally)/(°C), Dose 2	380 Participants	382 Participants	78 Participants	80 Participants	44 Participants	20 Participants	55 Participants	11 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Temperature (Rectally)/(°C), Dose 2	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	2 Participants	1 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Related Temperature (Rectally)/(°C), Dose 2	373 Participants	378 Participants	78 Participants	71 Participants	43 Participants	15 Participants	53 Participants	8 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Any Irritability, Dose 2	1254 Participants	822 Participants	532 Participants	408 Participants	139 Participants	94 Participants	193 Participants	72 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Irritability, Dose 2	73 Participants	44 Participants	13 Participants	14 Participants	7 Participants	1 Participants	3 Participants	0 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Related Irritability, Dose 2	1236 Participants	816 Participants	523 Participants	396 Participants	137 Participants	93 Participants	191 Participants	71 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Any Loss of appetite, Dose 2	434 Participants	323 Participants	187 Participants	149 Participants	69 Participants	56 Participants	109 Participants	57 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Loss of appetite, Dose 2	4 Participants	2 Participants	1 Participants	3 Participants	44 Participants	0 Participants	2 Participants	1 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Related Loss of appetite, Dose 2	419 Participants	318 Participants	181 Participants	135 Participants	0 Participants	52 Participants	105 Participants	54 Participants
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Drowsiness, Dose 3	2 Participants	—	2 Participants	—	—	—	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Related Drowsiness, Dose 3	638 Participants	—	285 Participants	—	—	—	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Any Temperature (Rectally)/(°C), Dose 3	347 Participants	—	110 Participants	—	—	—	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Temperature (Rectally)/(°C), Dose 3	1 Participants	—	1 Participants	—	—	—	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Related Temperature (Rectally)/(°C), Dose 3	336 Participants	—	106 Participants	—	—	—	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Any Irritability, Dose 3	1115 Participants	—	496 Participants	—	—	—	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Irritability, Dose 3	41 Participants	—	14 Participants	—	—	—	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Related Irritability, Dose 3	1100 Participants	—	492 Participants	—	—	—	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Any Loss of appetite, Dose 3	349 Participants	—	178 Participants	—	—	—	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Loss of appetite, Dose 3	3 Participants	—	0 Participants	—	—	—	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Related Loss of appetite, Dose 3	336 Participants	—	172 Participants	—	—	—	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Any Drowsiness, Booster dose	721 Participants	561 Participants	307 Participants	243 Participants	92 Participants	47 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Drowsiness, Booster dose	8 Participants	8 Participants	3 Participants	4 Participants	2 Participants	1 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Related Drowsiness, Booster dose	699 Participants	548 Participants	300 Participants	233 Participants	87 Participants	46 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Any Temperature (Rectally)/(°C), Booster dose	391 Participants	333 Participants	142 Participants	120 Participants	42 Participants	11 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Temperature (Rectally)/(°C), Booster dose	3 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Related Temperature (Rectally)/(°C), Booster dose	371 Participants	319 Participants	134 Participants	110 Participants	41 Participants	8 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Any Irritability, Booster dose	1124 Participants	816 Participants	491 Participants	410 Participants	129 Participants	84 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Irritability, Booster dose	47 Participants	33 Participants	14 Participants	7 Participants	2 Participants	1 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Related Irritability, Booster dose	1085 Participants	801 Participants	481 Participants	395 Participants	124 Participants	80 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Any Loss of appetite, Booster dose	549 Participants	411 Participants	260 Participants	186 Participants	64 Participants	46 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Grade 3 Loss of appetite, Booster dose	12 Participants	5 Participants	6 Participants	3 Participants	2 Participants	1 Participants	—	—
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. Related Loss of appetite, Booster dose	513 Participants	398 Participants	253 Participants	173 Participants	60 Participants	43 Participants	—	—

SECONDARY outcome

Timeframe: Within 31 days (31D) after each vaccination (M0+31D, M1+31D [only for 3+1 schedule], M2+31D, M8+31D [booster dose] for 6W-6M subjects; M0+31D, M2+31D, M6+31D [booster dose] for 7M-11M subjects; M0+31D, M6+31D for 12M-18M subjects)

Population: Analysis was performed on the Total vaccinated cohort which included all subjects who had received at least one vaccination dose.

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=1849 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=1316 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=1069 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group n=859 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group n=241 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group n=204 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group n=368 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group n=271 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Number of Subjects With Any Unsolicited Adverse Events (AEs). Unsolicited AEs, Booster vaccination	521 Participants	363 Participants	277 Participants	244 Participants	51 Participants	48 Participants	—	—
Number of Subjects With Any Unsolicited Adverse Events (AEs). Unsolicited AEs, Primary vaccination	1105 Participants	598 Participants	554 Participants	337 Participants	157 Participants	132 Participants	221 Participants	174 Participants

SECONDARY outcome

Timeframe: Following administration of the first vaccine dose up to study end (M0 up to M18 for subjects aged 6W to 6M at enrollment; M0 up to M16 for subjects aged 7M to 11M at enrollment; M0 up to M9 for subjects aged 12M to 18M at enrollment)

Population: Analysis was performed on the Total vaccinated cohort which included all subjects who had received at least one vaccination dose.

An event is defined as 'serious' when it meets one of the pre-defined outcomes described below: results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation; results in disability/incapacity, or is a congenital anomaly/birth defect in the offspring of a study subject. Medical or scientific judgement should be exercised in deciding whether reporting is appropriate in other situations, such as important medical events that may not be immediately life-threatening or result in death or hospitalisation but may jeopardize the subject or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition. These should also be considered serious.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=1849 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=1316 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=1069 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group n=859 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group n=241 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group n=204 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group n=368 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group n=271 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Number of Subjects With Serious Adverse Events (SAEs).	163 Participants	96 Participants	77 Participants	74 Participants	24 Participants	18 Participants	23 Participants	14 Participants

SECONDARY outcome

Timeframe: From the end of the blinded ID Follow-Up period (at least 30 months from the study start) up to the end of 18-month period after study unblinding

Population: Analysis was performed on the Total vaccinated cohort which included all subjects who had received at least one vaccination dose in the 10PN-PD-DIT-043 and 10PN-PD-DIT-053 study with post-study SAEs reported via passive surveillance.

Outcome measures

Outcome measures
Measure	10Pn3+1-6W-6M/043+053 Group n=10273 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8427 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=10054 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	Ctrl-6W-6M/043+053 Group n=10201 Participants Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 8872 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group descriptions for Ctrl3+1-6W-6M/053 and Ctrl2+1-6W-6M/053 groups for details on vaccine specifics and administration route in this group.	10Pn7-11M/043+053 Group n=3880 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3689 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for 10Pn7-11M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl7-11M/043+053 Group n=1908 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 1812 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (7-11M Schedule). Refer to group description for Ctrl7-11M/053 Group for details on vaccine specifics and administration route in this group.	10Pn12-18M/043+053 Group n=6535 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 6249 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, or 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/043+053 Group n=3126 Participants Subjects in this group were subjects enrolled in the 10PNPD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) (i.e. 3020 subjects) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) studies and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/053 Group for details on vaccine specifics and administration route in this group.	Ctrl12-18M/053 Group Subjects in this group were subjects enrolled in the 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Number of Subjects Enrolled and Vaccinated in the 10PN-PD-DIT-043 and 10PN-PD-DIT-053 Study With Post-study SAEs Reported Via Passive Surveillance- Subjects Enrolled Aged 6 Weeks to 6 Months and 7 to 18 Months	1 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: At 3 months (mths) of age (prior to dose 1); at 6 mths of age (1 mth post dose 3 or post dose 2); at 11-12 mths of age (pre-booster dose); at 14-15 mths of age (3 mths post-booster); at 18-22 mths of age (10 mths post-booster)