Trial Outcomes & Findings for Follow up Study to Assess Long Term Safety and Outcomes in Infants and Children Born to Mothers Participating in Retosiban Treatment Studies (NCT NCT02292784)

NCT ID: NCT02292784

Last Updated: 2020-07-09

Results Overview

The parents of the infants filled in an online child health inventory (CHI) questionnaire, which asked them about each condition. If they reported anything, it was then verified by a healthcare professional. Number of infants and children with newly diagnosed chronic medical conditions are presented.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 98 participants
• Primary outcome timeframe: From 28 days post estimated date of delivery up to 24 months
• Results posted on: 2020-07-09

Participant Flow

This was a randomized, long-term follow-up study to evaluate the safety and outcomes of infants and children born to women who received retosiban or comparator in the Phase III spontaneous preterm labor (SPTL) treatment studies:200719 (NCT02377466) and 200721 (NCT02292771). Current study was referred as a retosiban infant outcome study (ARIOS).

A total of 101 participants were screened and 98 participants were enrolled and randomized in this study.

Participant milestones

Measure	Placebo (200719 Study) All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Overall Study STARTED	5	44	49
Overall Study COMPLETED	4	24	28
Overall Study NOT COMPLETED	1	20	21

Reasons for withdrawal

Measure	Placebo (200719 Study) All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Overall Study Lost to Follow-up	1	17	18
Overall Study Withdrawal by Subject	0	3	3

Baseline Characteristics

Follow up Study to Assess Long Term Safety and Outcomes in Infants and Children Born to Mothers Participating in Retosiban Treatment Studies

Baseline characteristics by cohort

Measure	Placebo (200719 Study) n=5 Participants All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=44 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=49 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Total n=98 Participants Total of all reporting groups
Age, Continuous	2.16 Months STANDARD_DEVIATION 1.479 • n=5 Participants	2.18 Months STANDARD_DEVIATION 1.158 • n=7 Participants	2.12 Months STANDARD_DEVIATION 0.932 • n=5 Participants	2.15 Months STANDARD_DEVIATION 1.056 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	18 Participants n=7 Participants	21 Participants n=5 Participants	40 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	26 Participants n=7 Participants	28 Participants n=5 Participants	58 Participants n=4 Participants
Race/Ethnicity, Customized African American/African (Afr) Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	0 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	11 Participants n=4 Participants
Race/Ethnicity, Customized Asian-Central/South Asian Heritage	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Asian-East Asian Heritage	1 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	13 Participants n=4 Participants
Race/Ethnicity, Customized Asian-Japanese Heritage	4 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized White-Arabic/North Afr/Caucasian/European Heritage	0 Participants n=5 Participants	34 Participants n=7 Participants	31 Participants n=5 Participants	65 Participants n=4 Participants

PRIMARY outcome

Timeframe: From 28 days post estimated date of delivery up to 24 months

Population: ARIOS Safety Population was a subset of the Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.

The parents of the infants filled in an online child health inventory (CHI) questionnaire, which asked them about each condition. If they reported anything, it was then verified by a healthcare professional. Number of infants and children with newly diagnosed chronic medical conditions are presented.

Outcome measures

Measure	Placebo (200719 Study) n=5 Participants All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=44 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=49 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants and Children With Newly Diagnosed Chronic Medical Conditions (After 28 Days Post Estimated Date of Delivery)	0 Participants	1 Participants	3 Participants

PRIMARY outcome

Timeframe: From 28 days post estimated date of delivery up to 24 months

Population: ARIOS Safety Population

A congenital anomaly is a condition present at birth that results from malformation, deformation, or disruption in 1 or more parts of the body, a chromosomal abnormality, or a known clinical syndrome. Congenital anomaly serious adverse events (SAEs) were examined by the birth defect evaluator. Events were coded per centers for disease control and prevention (CDC) Metropolitan Atlanta congenital defects program (MACDP) criteria and/or European surveillance of congenital anomalies (EUROCAT) criteria. Predefined defect codes specified whether the defect was face and neck, a cleft lip or palate, cardiovascular, respiratory, upper gastrointestinal, female genitalia, male genitalia, renal and urinary system, other musculoskeletal defects, skin, a chromosome anomaly, other organ systems, or a specified syndrome. Number of infants and children with newly diagnosed congenital anomalies reported up to 1 year of chronological age and reported after 1 year of chronological age are presented.

Outcome measures

Measure	Placebo (200719 Study) n=5 Participants All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=44 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=49 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants and Children With Newly Diagnosed Congenital Anomalies (After 28 Days Post Estimated Date of Delivery) Up to 1 year of chronological age	0 Participants	0 Participants	2 Participants
Number of Infants and Children With Newly Diagnosed Congenital Anomalies (After 28 Days Post Estimated Date of Delivery) After 1 year of chronological age	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From 28 days post estimated date of delivery up to 24 months

Population: ARIOS Safety Population

Number of infant and child death that occurred after 28 days post estimated date of delivery and up to 24 months are presented.

Outcome measures

Measure	Placebo (200719 Study) n=5 Participants All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=44 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=49 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infant and Child Death (After 28 Days Post Estimated Date of Delivery)	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: At 9 months

Population: ARIOS Safety Population. Only those participants with data available at the specified data points were analyzed.

The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: communication skills, gross motor skills, fine motor skills, problem solving skills, and personal social skills. Parents answered either yes (10 points), sometimes (5 points) or not yet (0 points) to each question to complete ASQ-3. At 9 months, the pre-defined cut-off score for communication was 13.97, gross motor was 17.82, fine motor was 31.32, problem solving was 28.72 and personal social skills was 18.91. Total score was derived by taking mean of all 5 components. Any infant who scored below the cut-off, a score more than or equal to 2 standard deviations below the mean score (that is Black zone in the score chart) in any of the 5 areas of the ASQ-3 was to be referred to a developmental specialist for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for any domains in the black zone at 9 months is presented.

Outcome measures

Measure	Placebo (200719 Study) n=3 Participants All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=17 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=20 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Any Domain at 9 Months	0 Participants	4 Participants	4 Participants

PRIMARY outcome

Timeframe: At 18 months

Population: ARIOS Safety Population. Only those participants with data available at the specified data points were analyzed.

The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: communication skills, gross motor skills, fine motor skills, problem solving skills, and personal social skills. Parents answered either yes (10 points), sometimes (5 points) or not yet (0 points) to each question to complete ASQ-3. At 18 months, the pre-defined cut-off score for communication was 13.06, gross motor was 37.38, fine motor was 34.32, problem solving was 25.74 and personal social skills was 27.19. Total score was derived by taking mean of all 5 components. Any infant who scored below the cut-off, a score more than or equal to 2 standard deviations below the mean score (that is Black zone in the score chart) in any of the 5 areas of the ASQ-3 was to be referred to a developmental specialist for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for any domains in the black zone at 18 months is presented.

Outcome measures

Measure	Placebo (200719 Study) n=3 Participants All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=19 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=18 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Any Domain at 18 Months	2 Participants	5 Participants	0 Participants

PRIMARY outcome

Timeframe: At 24 months

Population: ARIOS Safety Population. Only those participants with data available at the specified data points were analyzed.

The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: communication skills, gross motor skills, fine motor skills, problem solving skills, and personal social skills. Parents answered either yes (10 points), sometimes (5 points) or not yet (0 points) to each question to complete ASQ-3. At 24 months, the pre-defined cut-off score for communication was 25.17, gross motor was 38.07, fine motor was 35.16, problem solving was 29.78 and personal social skills was 31.54. Total score was derived by taking mean of all 5 components. Any infant who scored below the cut-off, a score more than or equal to 2 standard deviations below the mean score (that is Black zone in the score chart) in any of the 5 areas of the ASQ-3 was to be referred to a developmental specialist for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for any domains in the black zone at 24 months is presented.

Outcome measures

Measure	Placebo (200719 Study) n=2 Participants All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=19 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=25 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Any Domain at 24 Months	1 Participants	2 Participants	2 Participants

PRIMARY outcome

Timeframe: 9, 18 and 24 months

Population: ARIOS Safety Population. All 98 participants in the study were included in the analysis (5, 44 and 49 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: communication skills, gross motor skills, fine motor skills, problem solving skills, and personal social skills. Parents answered either yes (10 points), sometimes (5 points) or not yet (0 points) to each question to complete ASQ-3. At 9 months, the pre-defined cut-off score for gross motor skills was 17.82. At 18 months, the pre-defined cut-off score for gross motor skills was 37.38. At 24 months, the pre-defined cut-off score for gross motor skills was 38.07. Any infant who scored below the cut-off, a score more than or equal to 2 standard deviations below the mean score (that is Black zone in the score chart) in any of the 5 areas of the ASQ-3 was to be referred to a developmental specialist for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for gross motor skills in the black zone at 9, 18 and 24 months is presented.

Outcome measures

Measure	Placebo (200719 Study) n=5 Participants All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=44 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=49 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Gross Motor Skills 9 months, n=3,17,20	0 Participants	1 Participants	0 Participants
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Gross Motor Skills 18 months, n=3,19,18	1 Participants	1 Participants	0 Participants
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Gross Motor Skills 24 months, n=2,19,25	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: 9, 18 and 24 months

Population: ARIOS Safety Population. All 98 participants in the study were included in the analysis (5, 44 and 49 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: communication skills, gross motor skills, fine motor skills, problem solving skills, and personal social skills. Parents answered either yes (10 points), sometimes (5 points) or not yet (0 points) to each question to complete ASQ-3. At 9 months, the pre-defined cut-off score for fine motor skills was 31.32. At 18 months, the pre-defined cut-off score for fine motor skills was 34.32. At 24 months, the pre-defined cut-off score for fine motor skills was 35.16. Any infant who scored below the cut-off, a score more than or equal to 2 standard deviations below the mean score (that is Black zone in the score chart) in any of the 5 areas of the ASQ-3 was to be referred to a developmental specialist for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for fine motor skills in the black zone at 9, 18 and 24 months is presented.

Outcome measures

Measure	Placebo (200719 Study) n=5 Participants All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=44 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=49 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Fine Motor Skills 9 months, n=3,17,20	0 Participants	0 Participants	2 Participants
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Fine Motor Skills 18 months, n=3,19,18	1 Participants	2 Participants	0 Participants
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Fine Motor Skills 24 months, n=2,19,25	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 9, 18 and 24 months

Population: ARIOS Safety Population. All 98 participants in the study were included in the analysis (5, 44 and 49 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: communication skills, gross motor skills, fine motor skills, problem solving skills, and personal social skills. Parents answered either yes (10 points), sometimes (5 points) or not yet (0 points) to each question to complete ASQ-3. At 9 months, the pre-defined cut-off score for communication skills was 13.97. At 18 months, the pre-defined cut-off score for communication skills was 13.06. At 24 months, the pre-defined cut-off score for communication skills was 25.17. Any infant who scored below the cut-off, a score more than or equal to 2 standard deviations below the mean score (that is Black zone in the score chart) in any of the 5 areas of the ASQ-3 was to be referred to a developmental specialist for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for communication skills in the black zone at 9, 18 and 24 months is presented.

Outcome measures

Measure	Placebo (200719 Study) n=5 Participants All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=44 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=49 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Communication Skills 9 months, n=3,17,20	0 Participants	1 Participants	1 Participants
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Communication Skills 18 months, n=3,19,18	1 Participants	0 Participants	0 Participants
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Communication Skills 24 months, n=2,19,25	1 Participants	1 Participants	2 Participants

PRIMARY outcome

Timeframe: 9, 18 and 24 months

Population: ARIOS Safety Population. All 98 participants in the study were included in the analysis (5, 44 and 49 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: communication skills, gross motor skills, fine motor skills, problem solving skills, and personal social skills. Parents answered either yes (10 points), sometimes (5 points) or not yet (0 points) to each question to complete ASQ-3. At 9 months, the pre-defined cut-off score for problem solving skills was 28.72. At 18 months, the pre-defined cut-off score for problem solving skills was 25.74. At 24 months, the pre-defined cut-off score for problem solving skills was 29.78. Any infant who scored below the cut-off, a score more than or equal to 2 standard deviations below the mean score (that is Black zone in the score chart) in any of the 5 areas of the ASQ-3 was to be referred to a developmental specialist for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for problem solving skills in the black zone at 9, 18 and 24 months is presented.

Outcome measures

Measure	Placebo (200719 Study) n=5 Participants All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=44 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=49 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Problem Solving Skills 9 months, n=3,17,20	0 Participants	1 Participants	2 Participants
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Problem Solving Skills 18 months, n=3,19,18	0 Participants	1 Participants	0 Participants
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Problem Solving Skills 24 months, n=2,19,25	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: 9, 18 and 24 months

Population: ARIOS Safety Population. All 98 participants in the study were included in the analysis (5, 44 and 49 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

The ASQ-3 included 6 questions in each area, designed to assess 5 areas of development: communication skills, gross motor skills, fine motor skills, problem solving skills, and personal social skills. Parents answered either yes (10 points), sometimes (5 points) or not yet (0 points) to each question to complete ASQ-3. At 9 months, the pre-defined cut-off score for personal social skills was 18.91. At 18 months, the pre-defined cut-off score for personal social skills was 27.19. At 24 months, the pre-defined cut-off score for personal social skills was 31.54. Any infant who scored below the cut-off, a score more than or equal to 2 standard deviations below the mean score (that is Black zone in the score chart) in any of the 5 areas of the ASQ-3 was to be referred to a developmental specialist for a formal neurodevelopmental assessment. Number of infants with ASQ-3 scores for personal social skills in the black zone at 9, 18 and 24 months is presented.

Outcome measures

Measure	Placebo (200719 Study) n=5 Participants All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=44 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=49 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Personal Social Skills 9 months, n=3,17,20	0 Participants	2 Participants	0 Participants
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Personal Social Skills 18 months, n=3,19,18	0 Participants	1 Participants	0 Participants
Number of Infants With Ages and Stages Questionnaire-3 (ASQ-3) Score in the Black Zone for Personal Social Skills 24 months, n=2,19,25	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: 9, 18 and 24 months

Population: ARIOS Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Any infant who scored below the cut-off i.e., a score greater than or equal to 2 Standard Deviations (SDs) below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was referred to a developmental specialist for a neurodevelopmental evaluation using the BSID-III. It scaled scores for cognitive, language (receptive and expressive), motor (fine and gross motor). The language and motor areas each have a composite score, with a mean of 100, a SD of 15 and a range of 40 to 160. Scores lower than 70 indicated moderate or severe impairment. In the cognitive area, the infant scored "1" if they could do an activity and "0" if they could not. Total score was derived by taking mean of all the components. Number of infants referred for developmental evaluation using BSID-III is presented.

Outcome measures

Measure	Placebo (200719 Study) n=2 Participants All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=5 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=4 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants Referred for Developmental Evaluation Using Bayley Scales of Infant Development, Third Edition (BSID-III) 9 months, n=0,4,4	—	1 Participants	3 Participants
Number of Infants Referred for Developmental Evaluation Using Bayley Scales of Infant Development, Third Edition (BSID-III) 18 months, n=2,5,0	2 Participants	3 Participants	—
Number of Infants Referred for Developmental Evaluation Using Bayley Scales of Infant Development, Third Edition (BSID-III) 24 months, n=1,2,2	0 Participants	2 Participants	1 Participants

PRIMARY outcome

Timeframe: 9, 18 and 24 months

Population: ARIOS Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Any infant who scored below the cut-off i.e., a score greater than or equal to 2 SDs below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was referred to a developmental specialist for a neurodevelopmental evaluation using the BSID-III. It scaled scores for cognitive, language (receptive and expressive), motor (fine and gross motor). The language and motor areas each have a composite score, with a mean of 100, a SD of 15 and a range of 40 to 160. Scores lower than 70 indicated moderate or severe impairment. In the cognitive area, the infant scored "1" if they could do an activity and "0" if they could not. Number of infants with BSID-III score greater than 2 SD below the mean score for the cognitive scale (less than 4) is presented.

Outcome measures

Measure	Placebo (200719 Study) All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=2 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=1 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants With Bayley Scales of Infant Development, Third Edition Score Greater Than 2 Standard Deviation Below the Mean Score for the Cognitive Scale (Less Than 4) 9 months, n=0,0,1	—	—	0 Participants
Number of Infants With Bayley Scales of Infant Development, Third Edition Score Greater Than 2 Standard Deviation Below the Mean Score for the Cognitive Scale (Less Than 4) 18 months, n=0,2,0	—	2 Participants	—
Number of Infants With Bayley Scales of Infant Development, Third Edition Score Greater Than 2 Standard Deviation Below the Mean Score for the Cognitive Scale (Less Than 4) 24 months, n=0,0,1	—	—	1 Participants

PRIMARY outcome

Timeframe: 9, 18 and 24 months

Population: ARIOS Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Any infant who scored below the cut-off i.e., a score greater than or equal to 2 SDs below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was referred to a developmental specialist for a neurodevelopmental evaluation using the BSID-III. It scaled scores for cognitive, language (receptive and expressive), motor (fine and gross motor). The language and motor areas each have a composite score, with a mean of 100, a SD of 15 and a range of 40 to 160. Scores lower than 70 indicated moderate or severe impairment. In the cognitive area, the infant scored "1" if they could do an activity and "0" if they could not. Number of infants with BSID-III score greater than 2 SD below the mean score for the gross motor scale (less than 4) is presented.

Outcome measures

Measure	Placebo (200719 Study) All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=2 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=1 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants With Bayley Scales of Infant Development, Third Edition Score Greater Than 2 Standard Deviation Below the Mean Score for the Gross Motor Scale (Less Than 4) 9 months, n=0,0,1	—	—	0 Participants
Number of Infants With Bayley Scales of Infant Development, Third Edition Score Greater Than 2 Standard Deviation Below the Mean Score for the Gross Motor Scale (Less Than 4) 18 months, n=0,2,0	—	2 Participants	—
Number of Infants With Bayley Scales of Infant Development, Third Edition Score Greater Than 2 Standard Deviation Below the Mean Score for the Gross Motor Scale (Less Than 4) 24 months, n=0,0,1	—	—	1 Participants

PRIMARY outcome

Timeframe: 9, 18 and 24 months

Population: ARIOS Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Any infant who scored below the cut-off i.e., a score greater than or equal to 2 SDs below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was referred to a developmental specialist for a neurodevelopmental evaluation using the BSID-III. It scaled scores for cognitive, language (receptive and expressive), motor (fine and gross motor). The language and motor areas each have a composite score, with a mean of 100, a SD of 15 and a range of 40 to 160. Scores lower than 70 indicated moderate or severe impairment. In the cognitive area, the infant scored "1" if they could do an activity and "0" if they could not. Number of infants with BSID-III score greater than 2 SD below the mean score for the fine motor scale (less than 4) is presented.

Outcome measures

Measure	Placebo (200719 Study) All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=2 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=1 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants With Bayley Scales of Infant Development, Third Edition Score Greater Than 2 Standard Deviation Below the Mean Score for the Fine Motor Scale (Less Than 4) 9 months, n=0,0,1	—	—	0 Participants
Number of Infants With Bayley Scales of Infant Development, Third Edition Score Greater Than 2 Standard Deviation Below the Mean Score for the Fine Motor Scale (Less Than 4) 18 months, n=0,2,0	—	2 Participants	—
Number of Infants With Bayley Scales of Infant Development, Third Edition Score Greater Than 2 Standard Deviation Below the Mean Score for the Fine Motor Scale (Less Than 4) 24 months, n=0,0,1	—	—	1 Participants

PRIMARY outcome

Timeframe: 9, 18 and 24 months

Population: ARIOS Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Any infant who scored below the cut-off i.e., a score greater than or equal to 2 SDs below the mean score (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was referred to a developmental specialist for a neurodevelopmental evaluation using the BSID-III. It scaled scores for cognitive, language (receptive and expressive), motor (fine and gross motor). The language and motor areas each have a composite score, with a mean of 100, a SD of 15 and a range of 40 to 160. Scores lower than 70 indicated moderate or severe impairment. In the cognitive area, the infant scored "1" if they could do an activity and "0" if they could not. Number of infants with BSID-III score greater than 2 SD below the mean score for the language scale (less than 70) is presented.

Outcome measures

Measure	Placebo (200719 Study) All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=2 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=1 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants With Bayley Scales of Infant Development, Third Edition Score Greater Than 2 Standard Deviation Below the Mean Score for the Language Scale (Less Than 70) 9 months, n=0,0,1	—	—	0 Participants
Number of Infants With Bayley Scales of Infant Development, Third Edition Score Greater Than 2 Standard Deviation Below the Mean Score for the Language Scale (Less Than 70) 18 months, n=0,2,0	—	2 Participants	—
Number of Infants With Bayley Scales of Infant Development, Third Edition Score Greater Than 2 Standard Deviation Below the Mean Score for the Language Scale (Less Than 70) 24 months, n=0,0,1	—	—	1 Participants

PRIMARY outcome

Timeframe: At 24 months

Population: ARIOS Safety Population. Only those participants with data available at the specified data points were analyzed.

The CBCL/1.5 to 5 questionnaire is a parent-completed questionnaire used for assessing behavioral problems and social competencies. It included approximately 100 items that described specific kinds of behavioral, emotional, and social problems that characterized preschool children between the ages of 1.5 and 5 years. Each question could be answered as "not true scored as"0",somewhat or sometimes true scored as"1"or very true or often true scored as "2". There were 6 questions related to attention and hyperactivity problems. The responses to those 6 questions were summed (ranged 0 to 12). Total score of 0 to 9 indicated normal, 10 indicated borderline and 11 to 12 indicated significant attention and hyperactivity problems. Scores above the 97th percentile are in the significant range of clinical concern. Number of infants with CBCL/1.5 to 5 score above 97th percentile for subset of pre-specified questions related to attention and hyperactivity problems at 24 months is reported.

Outcome measures

Measure	Placebo (200719 Study) n=2 Participants All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=12 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=14 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants With a Child Behavior Checklist for Ages 1.5 to 5 Years (CBCL/1.5 to 5) Score Above the 97th Percentile for a Subset of Prespecified Questions That Relate to Attention and Hyperactivity Problems	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: 18 and 24 months

Population: ARIOS Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

The M-CHAT-R/F is a parent-reported autism screening tool designed to identify children 16 to 30 months of age who received a more thorough assessment for possible early signs of autism spectrum disorder (ASD) or developmental delay. The M-CHAT-R/F consisted of 20 questions that were answered with either "yes, scored as 0" or "no, scored as 1". Total scores (ranged 0 to 20) on the M-CHAT-R/F between 0 and 2 indicated a low risk, scores between 3 and 7 indicated a medium risk and triggered administration of the follow-up questionnaire, and scores between 8 and 20 indicated a high risk. Number of infants who needed further evaluation as per the M-CHAT-R/F at 18 and 24 months is presented.

Outcome measures

Measure	Placebo (200719 Study) n=2 Participants All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=11 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=13 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants Indicated as Needing Further Evaluation After Completion of the Modified Checklist for Autism in Toddlers- Revised With Follow-up (M-CHAT-R/F) 18 months,n=2,10,7	0 Participants	0 Participants	0 Participants
Number of Infants Indicated as Needing Further Evaluation After Completion of the Modified Checklist for Autism in Toddlers- Revised With Follow-up (M-CHAT-R/F) 24 months,n=2,11,13	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: At 24 months

Population: ARIOS Safety Population. Only those participants with data available at the specified data points were analyzed.

Parents reported in CHI questionnaire if their infant had cerebral palsy. If the infant was not diagnosed with cerebral palsy, then this was detected as part of the ASQ-3 assessment, based on the results of the gross motor scale. To confirm the diagnosis of cerebral palsy, the healthcare practitioner referred the infant for further neurological tests if they scored in the black zone of the ASQ-3 at the month 24 assessment. Number of infants referred for neurological evaluation to determine diagnosis of cerebral palsy at 24 months is presented.

Outcome measures

Measure	Placebo (200719 Study) n=2 Participants All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=19 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=25 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants Referred for Neurological Evaluation to Determine Diagnosis of Cerebral Palsy	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 24 months

Population: ARIOS Safety Population. Only those participants with data available at the specified data points were analyzed.

The indicators of neurodevelopmental impairment were 'hearing impaired, uncorrected even with aids'; 'blindness in 1 or both eyes, or sees light only'; 'cerebral palsy-moderate and severe (moderate: Grade 2 or 3 using the gross motor functional classification system [GMFCS] and severe: Grade 4 or 5 using the GMFCS)'; 'cognitive impairment: BSID-III cognitive scale score of less than 2 SDs below mean score (less than 4)'; 'motor impairment: BSID-III motor composite scale score of greater than 2 SDs below mean score (less than 70)'; 'diagnosis of ASD, attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD)'. Number of infants having any 1 of these indicators is presented.

Outcome measures

Measure	Placebo (200719 Study) n=4 Participants All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=30 Participants All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=36 Participants All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Number of Infants With the Indicators of Neurodevelopmental Impairment Hearing impaired, uncorrected even with aids	0 Participants	0 Participants	0 Participants
Number of Infants With the Indicators of Neurodevelopmental Impairment Blindness in 1 or both eyes, or sees light only	0 Participants	0 Participants	0 Participants
Number of Infants With the Indicators of Neurodevelopmental Impairment Cerebral palsy (moderate and severe)	0 Participants	0 Participants	0 Participants
Number of Infants With the Indicators of Neurodevelopmental Impairment Cognitive impairment	0 Participants	1 Participants	1 Participants
Number of Infants With the Indicators of Neurodevelopmental Impairment Motor impairment	0 Participants	1 Participants	1 Participants
Number of Infants With the Indicators of Neurodevelopmental Impairment Diagnosis of ASD,ADD or ADHD	0 Participants	1 Participants	0 Participants

Adverse Events

Placebo (200719 Study)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Atosiban (200721 Study)

Serious events: 6 serious events

Other events: 0 other events

Deaths: 0 deaths

Retosiban (200719 and 200721 Study)

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo (200719 Study) n=5 participants at risk All infants and children born to women who received the placebo (0.9 percent sodium chloride infusion matched for retosiban volume, intravenous \[IV\] loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment) in 200719 study. Current study did not require any medical interventions or study visits to an investigational site.	Atosiban (200721 Study) n=44 participants at risk All infants and children born to women who received atosiban (in 3 successive stages; an initial bolus dose of 6.75 milligram \[mg\] using atosiban 6.75 mg per 0.9 milliliter \[mL\] solution for injection, followed by continuous high dose infusion at 18 mg per hour for 3 hours, then a lower 6 mg per hour infusion for the remainder of the 48-hour using the atosiban 37.5 mg per 5 mL concentrate for solution) in 200721 study. Current study did not require any medical interventions or study visits to an investigational site.	Retosiban (200719 and 200721 Study) n=49 participants at risk All infants and children born to women who received retosiban (6 mg IV loading dose of retosiban over 5 minutes followed by a 6 mg per hour continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg per hour continuous infusion for remainder of 48-hour treatment period) in 200719 study or 200721 study. Current study did not require any medical interventions or study visits to an investigational site.
Respiratory, thoracic and mediastinal disorders Bronchial hyperreactivity	0.00% 0/5 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	0.00% 0/44 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	2.0% 1/49 • Number of events 1 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.
Infections and infestations Bronchiolitis	0.00% 0/5 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	0.00% 0/44 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	2.0% 1/49 • Number of events 1 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.
Infections and infestations Pneumonia	0.00% 0/5 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	2.3% 1/44 • Number of events 1 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	2.0% 1/49 • Number of events 1 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.
Infections and infestations Acute bronchiolitis	0.00% 0/5 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	0.00% 0/44 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	2.0% 1/49 • Number of events 4 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.
Congenital, familial and genetic disorders Congenital cataract	0.00% 0/5 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	0.00% 0/44 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	2.0% 1/49 • Number of events 1 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.
Injury, poisoning and procedural complications Injury of genitals	0.00% 0/5 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	0.00% 0/44 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	2.0% 1/49 • Number of events 1 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.
Congenital, familial and genetic disorders Congenital hydrocoele	0.00% 0/5 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	0.00% 0/44 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	2.0% 1/49 • Number of events 1 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.
Infections and infestations Upper respiratory tract	0.00% 0/5 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	0.00% 0/44 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	2.0% 1/49 • Number of events 1 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.
Infections and infestations Rhinitis	0.00% 0/5 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	2.3% 1/44 • Number of events 1 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	0.00% 0/49 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.
Infections and infestations Pneumococcal sepsis	0.00% 0/5 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	2.3% 1/44 • Number of events 1 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	0.00% 0/49 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.
Infections and infestations Acute pharyngitis	0.00% 0/5 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	2.3% 1/44 • Number of events 1 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	0.00% 0/49 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.
Blood and lymphatic system disorders Cervical lymphadenitis	0.00% 0/5 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	2.3% 1/44 • Number of events 1 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	0.00% 0/49 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.
Cardiac disorders Circumoral cyanosis	0.00% 0/5 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	2.3% 1/44 • Number of events 1 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.	0.00% 0/49 • Serious adverse events (SAEs) were collected for infants from after 28 days post estimated due date until maximum of 24 months chronological age. Non-SAEs were not collected, since all the adverse events that occurred in infants were considered as SAEs SAEs were reported for ARIOS Safety Population which comprised of a subset of Infant Safety Population (all the infants whose mothers were randomized and received retosiban or comparator in any of the Phase III treatment trials) for which the mother/infant pairs were enrolled into the ARIOS study.

Other adverse events

Adverse event data not reported

Additional Information

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