Trial Outcomes & Findings for A Randomized Placebo Controlled Pilot Study of Probiotic Supplementation in At-risk Pregnant Women (NCT NCT03646487)

NCT ID: NCT03646487

Last Updated: 2023-04-07

Results Overview

Mean adherence to the supplement regimen using Pillsy smart bottles and standard pill counts.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 20 participants
• Primary outcome timeframe: 15 weeks gestation through delivery, an average of 25 weeks
• Results posted on: 2023-04-07

Participant Flow

Participant milestones

Measure	Probiotic LP299v Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Overall Study COMPLETED	7	6
Overall Study NOT COMPLETED	5	2
Overall Study STARTED	12	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Randomized Placebo Controlled Pilot Study of Probiotic Supplementation in At-risk Pregnant Women

Baseline characteristics by cohort

Measure	Probiotic LP299v n=12 Participants Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=8 Participants Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form	Total n=20 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	29.0 years STANDARD_DEVIATION 6.5 • n=5 Participants	28.7 years STANDARD_DEVIATION 6.9 • n=7 Participants	28.9 years STANDARD_DEVIATION 6.5 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants	5 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	8 participants n=7 Participants	20 participants n=5 Participants
Relationship status Single not living with significant other	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Relationship status Single but living with significant other	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Relationship status Married	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Health insurance Private	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Health insurance Public	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Health insurance Other	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Education Some high school; some college	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Education College graduate; graduate school	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Household income ≤$30,999	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Household income ≥$31,000	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Receiving public assistance WIC (Women Infants and Children Program)	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Receiving public assistance SNAP (Supplemental Nutrition Assistance Program)	6 participants n=5 Participants	5 participants n=7 Participants	11 participants n=5 Participants
Receiving public assistance TANF (Temporary Assistance for Needy Families)	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Gestational age at baseline	12.6 weeks STANDARD_DEVIATION 4.5 • n=5 Participants	13.7 weeks STANDARD_DEVIATION 3.7 • n=7 Participants	13 weeks STANDARD_DEVIATION 4.1 • n=5 Participants
Gestational age at delivery	38.6 weeks STANDARD_DEVIATION 0.7 • n=5 Participants	38.9 weeks STANDARD_DEVIATION 0.7 • n=7 Participants	38.8 weeks STANDARD_DEVIATION 0.7 • n=5 Participants
Pre-pregnancy body mass index (BMI)	31.1 kg/m^2 STANDARD_DEVIATION 7.3 • n=5 Participants	31.8 kg/m^2 STANDARD_DEVIATION 8.3 • n=7 Participants	31.4 kg/m^2 STANDARD_DEVIATION 7.5 • n=5 Participants
Pre-pregnancy obesity	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Maternal body mass index (BMI) at baseline	31.7 kg/m^2 STANDARD_DEVIATION 6.8 • n=5 Participants	32.9 kg/m^2 STANDARD_DEVIATION 6.8 • n=7 Participants	32.2 kg/m^2 STANDARD_DEVIATION 6.7 • n=5 Participants
Maternal obesity at baseline	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Parity 0	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Parity 1	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Parity 2	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Food iron intake	11.2 mg/1000 kcal n=5 Participants	9.8 mg/1000 kcal n=7 Participants	10.5 mg/1000 kcal n=5 Participants
Total iron (food and supplement) intake	35.1 mg/1000 kcal n=5 Participants	36.8 mg/1000 kcal n=7 Participants	36.2 mg/1000 kcal n=5 Participants

PRIMARY outcome

Timeframe: 15 weeks gestation through delivery, an average of 25 weeks

Population: A total of 20 participants were randomized in the study; n=12 in the Probiotic LP299v group and n=8 in the Placebo group. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis because it was discovered the individual had alpha Thalassemia, a genetic disorder that impacts hemoglobin levels. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.

Mean adherence to the supplement regimen using Pillsy smart bottles and standard pill counts.

Outcome measures

Measure	Probiotic LP299v n=11 Participants Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=8 Participants Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Mean Adherence to the Supplement Regimen	67 percentage of adherence Standard Deviation 29.1	80 percentage of adherence Standard Deviation 25.3

SECONDARY outcome

Timeframe: 15 weeks gestation through delivery, an average of 25 weeks

Population: A total of 20 participants were randomized in the study; n=12 in the Probiotic LP299v group and n=8 in the Placebo group. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis because it was discovered the individual had alpha Thalassemia, a genetic disorder that impacts hemoglobin levels. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.

Adverse events were captured using the Maternal Adherence Form beginning with the first pill refill visit through delivery. number of participants reporting adverse GI events

Outcome measures

Measure	Probiotic LP299v n=11 Participants Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=8 Participants Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Number of Treatment-emergent Adverse Events Related to GI Symptoms	8 GI events	9 GI events

SECONDARY outcome

Timeframe: Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.

Population: We analyzed participants who completed the study with ≥80% adherence to examine changes in maternal hematological and iron status parameters by randomization group.

change in mean maternal serum hemoglobin (g/dl) from baseline to delivery

Outcome measures

Measure	Probiotic LP299v n=5 Participants Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=4 Participants Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Maternal Hemoglobin	0.4 g/dL Interval -1.1 to 1.8	-0.1 g/dL Interval -1.7 to 1.6

SECONDARY outcome

Timeframe: Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.

Population: We analyzed participants who completed the study with ≥80% adherence to examine changes in maternal hematological and iron status parameters by randomization group.

Change in mean maternal serum hematocrit (%) from baseline to delivery

Outcome measures

Measure	Probiotic LP299v n=5 Participants Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=4 Participants Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Maternal Hematocrit	-0.03 percentage by volume of red blood cells Interval -6.6 to 6.5	-0.5 percentage by volume of red blood cells Interval -4.7 to 3.8

SECONDARY outcome

Timeframe: Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.

Population: We analyzed participants who completed the study with ≥80% adherence to examine changes in maternal hematological and iron status parameters by randomization group.

change in mean maternal serum iron (µg/dL) from baseline to delivery

Outcome measures

Measure	Probiotic LP299v n=5 Participants Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=3 Participants Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Maternal Iron	-5.2 µg/dL Interval -17.6 to 7.2	5.7 µg/dL Interval -48.8 to 60.2

SECONDARY outcome

Timeframe: Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.

Population: We analyzed participants who completed the study with ≥80% adherence to examine changes in maternal hematological and iron status parameters by randomization group.

change in mean maternal total iron binding capacity (µmol/L) from baseline to delivery

Outcome measures

Measure	Probiotic LP299v n=5 Participants Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=3 Participants Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Maternal Total Iron Binding Capacity	89.4 µmol/L Interval 12.4 to 166.4	58.3 µmol/L Interval 11.4 to 105.2

SECONDARY outcome

Timeframe: Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.

Population: We analyzed participants who completed the study with ≥80% adherence to examine changes in maternal hematological and iron status parameters by randomization group.

change in mean maternal serum ferritin (ng/mL) from baseline to delivery

Outcome measures

Measure	Probiotic LP299v n=5 Participants Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=3 Participants Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Maternal Serum Ferritin	-4.4 ng/mL Interval -9.4 to 0.6	0 ng/mL Interval -94.4 to 94.4

SECONDARY outcome

Timeframe: Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.

Population: We analyzed participants who completed the study with ≥80% adherence to examine changes in maternal hematological and iron status parameters by randomization group.

change in mean maternal transferrin saturation (%) from baseline to delivery

Outcome measures

Measure	Probiotic LP299v n=5 Participants Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=3 Participants Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Maternal Transferrin Saturation	-6.2 percentage of saturation Interval -15.1 to 2.7	-1.7 percentage of saturation Interval -12.0 to 8.7

SECONDARY outcome

Timeframe: Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.

Population: We analyzed participants who completed the study with ≥80% adherence to examine changes in maternal hematological and iron status parameters by randomization group.

change in mean maternal high-sensitivity C-reactive protein (hs-CRP) (mg/L) from baseline to delivery

Outcome measures

Measure	Probiotic LP299v n=5 Participants Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=3 Participants Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Maternal High-sensitivity C-reactive Protein (Hs-CRP)	-0.04 mg/L Interval -3.9 to 3.9	-3.0 mg/L Interval -14.1 to 8.1

SECONDARY outcome

Timeframe: Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.

Population: We analyzed participants who completed the study with ≥80% adherence to examine changes in maternal hematological and iron status parameters by randomization group.

Number of participants who had iron deficiency anemia (IDA) at delivery. Hemoglobin, obtained from the Complete Blood Count, was used to define trimester-specific maternal IDA, with a downward correction of 0.8 g/dL for Black women. At the time of the study, it was recommended to use a race-adjusted cut-point for IDA. However, this race-adjusted cut-point was recently determined to be unfounded. IDA ranges included hemoglobin ≤11 g/dL for the first trimester, ≤10.5 g/dL for the second trimester, and ≤11 g/dL for the third trimester. IDA ranges with the correction for Black women were hemoglobin ≤10.2 g/dL for the first trimester, ≤9.7 g/dL for the second trimester, and ≤10.2 g/dL for the third trimester.

Outcome measures

Measure	Probiotic LP299v n=5 Participants Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=4 Participants Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Maternal Iron Deficiency Anemia	1 Participants	2 Participants

SECONDARY outcome

Timeframe: delivery

Population: The neonatal hematological and iron status parameters were examined for the newborns of mothers with ≥80% adherence to the supplement intervention.

Mean infant serum hemoglobin (g/dl) from cord blood at delivery.

Outcome measures

Measure	Probiotic LP299v n=5 Participants Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=4 Participants Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Infant Hemoglobin	14.7 g/dl Interval 12.1 to 17.3	16.4 g/dl Interval 14.6 to 18.2

SECONDARY outcome

Timeframe: delivery

Population: The neonatal hematological and iron status parameters were examined for the newborns of mothers with ≥80% adherence to the supplement intervention.

Mean infant serum hematocrit (%) from cord blood at delivery.

Outcome measures

Measure	Probiotic LP299v n=5 Participants Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=4 Participants Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Infant Hematocrit	44.3 percentage by volume of red blood cells Interval 38.5 to 50.2	49.5 percentage by volume of red blood cells Interval 44.9 to 54.0

SECONDARY outcome

Timeframe: delivery

Population: The neonatal hematological and iron status parameters were examined for the newborns of mothers with ≥80% adherence to the supplement intervention.

Mean infant serum iron (µg/dL) from cord blood at delivery.

Outcome measures

Measure	Probiotic LP299v n=5 Participants Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=3 Participants Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Infant Iron	136.2 µg/dL Interval 93.4 to 179.0	108.0 µg/dL Interval 48.4 to 167.6

SECONDARY outcome

Timeframe: delivery

Population: The neonatal hematological and iron status parameters were examined for the newborns of mothers with ≥80% adherence to the supplement intervention.

Mean infant total iron binding capacity (µmol/L) from cord blood at delivery.

Outcome measures

Measure	Probiotic LP299v n=5 Participants Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=3 Participants Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Infant Total Iron Binding Capacity	223.6 µmol/L Interval 155.6 to 291.6	274.0 µmol/L Interval 97.3 to 450.7

SECONDARY outcome

Timeframe: delivery

Population: The neonatal hematological and iron status parameters were examined for the newborns of mothers with ≥80% adherence to the supplement intervention.

Mean infant serum ferritin (ng/mL) from cord blood at delivery.

Outcome measures

Measure	Probiotic LP299v n=5 Participants Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=3 Participants Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Infant Serum Ferritin	88.8 ng/mL Interval 7.0 to 170.6	88.0 ng/mL Interval 44.1 to 132.0

SECONDARY outcome

Timeframe: delivery

Population: The neonatal hematological and iron status parameters were examined for the newborns of mothers with ≥80% adherence to the supplement intervention.

Mean infant transferrin saturation (%) from cord blood at delivery.

Outcome measures

Measure	Probiotic LP299v n=5 Participants Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=3 Participants Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Infant Transferrin Saturation	63.8 percentage of saturation Interval 35.3 to 92.3	43.3 percentage of saturation Interval -12.6 to 99.2

Adverse Events

Probiotic LP299v

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Probiotic LP299v n=11 participants at risk Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	Placebo n=8 participants at risk Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form
Reproductive system and breast disorders Genitourinary conditions	36.4% 4/11 • Number of events 8 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.	50.0% 4/8 • Number of events 5 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.
Gastrointestinal disorders Gastrointestinal symptoms	72.7% 8/11 • Number of events 8 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.	87.5% 7/8 • Number of events 9 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.
Respiratory, thoracic and mediastinal disorders Upper respiratory conditions	9.1% 1/11 • Number of events 1 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.	62.5% 5/8 • Number of events 5 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.
General disorders Pain/swelling	36.4% 4/11 • Number of events 8 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.	62.5% 5/8 • Number of events 7 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.
General disorders Headaches/migraines	27.3% 3/11 • Number of events 3 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.	37.5% 3/8 • Number of events 3 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.
General disorders Problems sleeping	36.4% 4/11 • Number of events 4 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.	50.0% 4/8 • Number of events 4 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.
General disorders Emergency room visits	18.2% 2/11 • Number of events 2 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.	37.5% 3/8 • Number of events 3 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.
Skin and subcutaneous tissue disorders Acne/rash	9.1% 1/11 • Number of events 1 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.	12.5% 1/8 • Number of events 1 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.
Psychiatric disorders Anxiety/depression	18.2% 2/11 • Number of events 3 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.	0.00% 0/8 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.
General disorders Fatigue/tired	45.5% 5/11 • Number of events 5 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.	25.0% 2/8 • Number of events 2 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.
Respiratory, thoracic and mediastinal disorders Nosebleeds	0.00% 0/11 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.	37.5% 3/8 • Number of events 3 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.
Congenital, familial and genetic disorders Genetic iron diagnoses	9.1% 1/11 • Number of events 1 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.	12.5% 1/8 • Number of events 1 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.
Congenital, familial and genetic disorders Genetic fetal diagnoses	18.2% 2/11 • Number of events 2 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.	0.00% 0/8 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.
General disorders Other	9.1% 1/11 • Number of events 2 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.	25.0% 2/8 • Number of events 2 • Health events were assessed by survey from the first pill refill visit through delivery, up to a period of 25 weeks span. Health events were assessed monthly by survey (i.e., Maternal Adherence Form) and through viewing provider notes in the participant's electronic health record. Study tolerability was defined a priori as no serious health events and the rate being similar between study arms. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis due to alpha Thalassemia. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.

Additional Information

Mary Dawn Koenig, PhD, RN, FACNM

University of Illinois Chicago

Phone: 312-996-7982

Email: marydh@uic.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place