Effects of Oral Probiotic Supplementation on Group B Strep (GBS) Rectovaginal Colonization in Pregnancy

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01479478
• Collaborator: (none)
• Enrollment: 251
• Locations: 3
• Arms: 2
• Duration (Months): 68.8
• Patients Per Site: 83.7
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The investigators wish to determine if oral probiotic supplementation during the second half of pregnancy decreases maternal GBS recto-vaginal colonization at 35-37 weeks' gestational age, thereby decreasing need for maternal antibiotic administration at time of labor. The importance of this study is that it may offer a safer alternative to antibiotic treatment of group B Streptococcus (GBS) colonized pregnant women.

Condition or Disease	Intervention/Treatment	Phase
Infection; Pregnancy	Drug: Placebo; Dietary Supplement: Probiotic dietary supplement	N/A

Detailed Description

1. Screening: All pregnant women prior to 28 weeks gestational age. Patients who choose to enroll and who will not deliver at Lucile Packard Childrens Hospital at Stanford will sign release of medical information forms for study personnel to access pregnancy outcomes. Patients receiving obstetric care at any of the satellite research sites in Santa Cruz will also be offered enrollment in the study.

2. Women will continue regular and routine obstetric care and clinic visits.

3. Placebo vs probiotic daily regimen: We plan to begin administration of product and placebo at 20 weeks gestation, and no later than 28 weeks gestation until delivery. Once a women is enrolled in the study, she will be randomized to either the placebo or the probiotic group.

4. At the time of randomization, the patient will receive her month supply of 30 capsules; The allocation arm will be double-blinded.

5. The investigators will schedule the women for routine monthly obstetric visits (more often if clinically required) during which time they will also meet with one of the investigators. The investigator at each monthly visit will provide an additional monthly allotment of 30 capsules. The capsule bottle from the previous cycle will be collected and dated if there are capsules remaining in the bottle. Remaining capsules will be counted and refrigerated for future use.

6. The investigators will collect history data including safety data per the questionnaire and will document compliance with the study.

7. GBS recto-vaginal screening: The investigators will enroll the women in the study and we will perform the standard GBS colonization screening (using standard GBS recto-vaginal cultures) at 36 weeks.

8. Additionally, subjects may opt to have serial vaginal swabs collected to assess potential beneficial effects of probiotics on the vaginal microbiota and bacterial vaginosis (BV) status. Vaginal swabs will be collected (either by study personnel or self-collected by the study participant). Swabs will be inserted 1-2 inches into the vaginal introitus and spun for 20 seconds and then withdrawn. Swabs will be collected at the following time points: prior to probiotic/placebo initiation, every 1-4 weeks from time of enrollment to time of delivery, and postpartum serially up to 12 months. These swabs will be stored at -20 degrees Celsius or colder for additional microbiologic analyses.

9. Additionally, placental tissue may be collected at time of delivery for possible future microbiome and/or other analyses.

10. Women who suffer a premature rupture of the membranes, deliver before 36 weeks gestation, or go into labor before the GBS culture result is available, will receive the standard GBS antibiotic prophylaxis.

11. Labor: The patient will receive standard delivery and newborn care. Patients with a positive GBS culture will be treated with standard antibiotics in labor.

12. Postpartum and neonatal care: The patient will receive routine postpartum care per the obstetric team. Data regarding her postpartum course and neonatal outcomes will be collected.

Study Design

• Study Type: Interventional
• Actual Enrollment: 251 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Oral Probiotic Supplementation and Group B Streptococcus Rectovaginal Colonization in Pregnant Women: a Randomized Double-blind Placebo-controlled Trial.
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Jul 26, 2017
• Actual Study Completion Date: Jul 26, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Probiotic dietary supplement Probiotic dietary supplement one capsule once per day until delivery.	Dietary Supplement: Probiotic dietary supplement; Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14; Other Names: Other Names: Jarrow's fem-dophilus
Placebo Comparator: Placebo Placebo capsule, one daily until delivery.	Drug: Placebo; One placebo capsule daily.; Other Names: Sugar pill

Outcome Measures

Primary Outcome Measures

1. Count of Participants With Positive Group B Streptococcus Rectovaginal Colonization Status at 35- 37 Weeks' Gestational Age [35 to 37 weeks gestational age]

   Gestational age is given in a format of full weeks.

Secondary Outcome Measures

1. Count of Participants With Urinary Tract Infection [From enrollment up to delivery hospitalization (up to 42 weeks gestation)]

2. Count of Participants With Intrapartum Chorioamnionitis [From time of labor onset until delivery (up to 42 weeks of gestation)]

   Intrapartum chorioamnionitis is maternal temperature above 38.0 degrees Celsius and one or more of the following findings: fetal tachycardia; maternal tachycardia; uterine tenderness; purulent or malodorous amniotic fluid, or elevated maternal white blood cell count.

3. Count of Participants With Endometritis [From time of delivery up to 6 weeks postpartum]

   Endometritis is a uterine (myometrial) infection.

4. Count of Participants With Cellulitis [From time of delivery up to 6 weeks postpartum]

   Cellulitis is a bacterial skin infection.

5. Count of Participants With Bacteremia [From time of labor onset up to 6 weeks postpartum]

   Bacteremia is defined as presence of bacteria in the blood.

6. Count of Participants With Sepsis [From labor onset up to 6 weeks postpartum]

   Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated response of the body to an infection.

7. Count of Participants With Other Infectious Morbidity [From time of labor onset up to 6 weeks postpartum]

   Other infectious morbidity included maternal mastitis or pneumonia.

8. Gestational Age at Delivery [At time of delivery (up to 42 weeks of gestation)]

   Gestational age at delivery is presented as weeks.

9. Apgar Score at 1 and 5 Minutes Following Delivery [At time of delivery (up to 42 weeks of gestation)]

   Apgar score is a measure to quickly assess the neonatal health status from time of delivery. Score ranges from 0-10. Lower scores correspond to worse health state; neonates with scores below 5 are considered to have poor prognosis.

10. Neonatal Bilirubin Level [Up to 14 days following delivery]

11. Neonatal C-reactive Protein Level [Up to 14 days following delivery]

    Maximum neonatal C-reactive protein level

12. Count of Neonates Requiring a "Rule-out Sepsis Evaluation" [Up to 14 days following delivery]

    Outcome was based on performance of neonatal blood culture.

13. Count of Neonates With Sepsis [Up to 14 days following delivery]

14. Count of Neonates With Pneumonia [Up to 14 days following delivery]

15. Count of Neonates With Meningitis [Up to 14 days following delivery]

16. Count of Neonates With Intensive-care Unit Admission [Up to 14 days following delivery]

17. Length of Neonatal Hospital Stay [Up to 14 days following delivery]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Pregnant women between 20-28 weeks gestation.

2. 18 years of age or older.

3. Singleton gestation.

Exclusion Criteria:

1. Preexisting morbidity: Immunocompromised status (HIV +; malignancy; history of organ transplant; chronic steroid therapy; autoimmune disease requiring treatment during pregnancy, and other immunocompromised states); Type 1 diabetes and type 2 diabetes;congenital cardiac disease and cardiac valvular disease requiring antibiotic prophylaxis during procedure/labor; pulmonary disease (except mild asthma); renal disease; chronic hepatic disease (Hepatitis B, C); inflammatory bowel disease (Crohn's disease or ulcerative colitis); stomach or duodenal ulcer; bowel resection, gastric bypass, and chronic indwelling venous, bladder, or gastric catheter.

2. Multi-fetal gestation.

3. Use of probiotics preparations in the 3 months prior to beginning of the study treatment or use of any additional probiotics preparations (other than study treatment) at any time during the study period (including over the counter food supplements such as Activia, BioK, other oral or vaginal probiotics products (BUT not including other common forms of yogurt).

4. Chronic (daily) use of broad spectrum antibiotics.

5. History of infant with GBS sepsis.

6. Intrauterine Growth Restriction (IUGR), Fetal Anomalies-major diagnosed at time of second trimester anatomy ultrasound

7. Anticipated delivery <35 wks for maternal/fetal indication

8. Placenta previa or accreta (with anticipated delivery prior to 35 weeks)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aptos Women's Health Center	Aptos	California	United States	95003
2	Dominican Hospital	Santa Cruz	California	United States	95065
3	Stanford University School of Medicine/Lucile Packard Children's Hospital	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Natali Aziz, MD, Stanford University School of Medicine/Lucile Packard Children's Hospital

Study Documents (Full-Text)

• Study Protocol - Nov 19, 2013
• Statistical Analysis Plan - Jul 14, 2017

More Information

Publications

None provided.

• Responsible Party: Natali Aziz, Clinical Assistant Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT01479478
• Other Study ID Numbers: 18840
• First Posted: Nov 24, 2011
• Last Update Posted: Aug 20, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No

Study Results

Participant Flow

Pre-assignment Detail	Only expecting mothers were enrolled in this study. Neonatal data were collected from respective pregnancies, however, the neonates were not considered to be enrolled in this study.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Period Title: Overall Study
STARTED	125	126
COMPLETED	125	126
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Probiotic Dietary Supplement	Placebo	Total
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.	Total of all reporting groups
Overall Participants	125	126	251
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.4 (5.7)	31.9 (5.3)	31.7 (5.5)
Sex: Female, Male (Count of Participants)
Female	125 100%	126 100%	251 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Non-Hispanic white	66 52.8%	71 56.3%	137 54.6%
Non-Hispanic other	21 16.8%	22 17.5%	43 17.1%
Hispanic	32 25.6%	26 20.6%	58 23.1%
Unknown	6 4.8%	7 5.6%	13 5.2%
Region of Enrollment (Count of Participants)
United States	125 100%	126 100%	251 100%
Pre-pregnancy Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.1 (6.5)	26.0 (7.5)	26.1 (7)

Outcome Measures

1. Primary Outcome

Title	Count of Participants With Positive Group B Streptococcus Rectovaginal Colonization Status at 35- 37 Weeks' Gestational Age
Description	Gestational age is given in a format of full weeks.
Time Frame	35 to 37 weeks gestational age

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	108	117
Count of Participants [Participants]	20 16%	23 18.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Probiotic Dietary Supplement, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.87
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

Title	Count of Participants With Urinary Tract Infection
Time Frame	From enrollment up to delivery hospitalization (up to 42 weeks gestation)

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	118	123
Count of Participants [Participants]	8 6.4%	9 7.1%

3. Secondary Outcome

Title	Count of Participants With Intrapartum Chorioamnionitis
Description	Intrapartum chorioamnionitis is maternal temperature above 38.0 degrees Celsius and one or more of the following findings: fetal tachycardia; maternal tachycardia; uterine tenderness; purulent or malodorous amniotic fluid, or elevated maternal white blood cell count.
Time Frame	From time of labor onset until delivery (up to 42 weeks of gestation)

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	118	121
Count of Participants [Participants]	5 4%	4 3.2%

4. Secondary Outcome

Title	Count of Participants With Endometritis
Description	Endometritis is a uterine (myometrial) infection.
Time Frame	From time of delivery up to 6 weeks postpartum

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	116	119
Count of Participants [Participants]	0 0%	2 1.6%

5. Secondary Outcome

Title	Count of Participants With Cellulitis
Description	Cellulitis is a bacterial skin infection.
Time Frame	From time of delivery up to 6 weeks postpartum

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	118	123
Count of Participants [Participants]	0 0%	0 0%

6. Secondary Outcome

Title	Count of Participants With Bacteremia
Description	Bacteremia is defined as presence of bacteria in the blood.
Time Frame	From time of labor onset up to 6 weeks postpartum

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	116	119
Count of Participants [Participants]	0 0%	0 0%

7. Secondary Outcome

Title	Count of Participants With Sepsis
Description	Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated response of the body to an infection.
Time Frame	From labor onset up to 6 weeks postpartum

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	116	119
Count of Participants [Participants]	0 0%	0 0%

8. Secondary Outcome

Title	Count of Participants With Other Infectious Morbidity
Description	Other infectious morbidity included maternal mastitis or pneumonia.
Time Frame	From time of labor onset up to 6 weeks postpartum

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	116	119
Count of Participants [Participants]	0 0%	0 0%

9. Secondary Outcome

Title	Gestational Age at Delivery
Description	Gestational age at delivery is presented as weeks.
Time Frame	At time of delivery (up to 42 weeks of gestation)

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	117	121
Median (Inter-Quartile Range) [weeks]	39.6	39.4

10. Secondary Outcome

Title	Apgar Score at 1 and 5 Minutes Following Delivery
Description	Apgar score is a measure to quickly assess the neonatal health status from time of delivery. Score ranges from 0-10. Lower scores correspond to worse health state; neonates with scores below 5 are considered to have poor prognosis.
Time Frame	At time of delivery (up to 42 weeks of gestation)

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	113	119
At 1 minute	8	8
At 5 minutes	9	9

11. Secondary Outcome

Title	Neonatal Bilirubin Level
Time Frame	Up to 14 days following delivery

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	104	94
Median (Inter-Quartile Range) [mg/dL]	6.4	6.5

12. Secondary Outcome

Title	Neonatal C-reactive Protein Level
Description	Maximum neonatal C-reactive protein level
Time Frame	Up to 14 days following delivery

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	23	18
Median (Inter-Quartile Range) [mg/L]	1.6	1.2

13. Secondary Outcome

Title	Count of Neonates Requiring a "Rule-out Sepsis Evaluation"
Description	Outcome was based on performance of neonatal blood culture.
Time Frame	Up to 14 days following delivery

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	115	121
Count of Participants [Participants]	9 7.2%	4 3.2%

14. Secondary Outcome

Title	Count of Neonates With Sepsis
Time Frame	Up to 14 days following delivery

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	115	121
Count of Participants [Participants]	4 3.2%	1 0.8%

15. Secondary Outcome

Title	Count of Neonates With Pneumonia
Time Frame	Up to 14 days following delivery

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	115	121
Count of Participants [Participants]	0 0%	0 0%

16. Secondary Outcome

Title	Count of Neonates With Meningitis
Time Frame	Up to 14 days following delivery

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	115	121
Count of Participants [Participants]	0 0%	0 0%

17. Secondary Outcome

Title	Count of Neonates With Intensive-care Unit Admission
Time Frame	Up to 14 days following delivery

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	115	121
Count of Participants [Participants]	12 9.6%	7 5.6%

18. Secondary Outcome

Title	Length of Neonatal Hospital Stay
Time Frame	Up to 14 days following delivery

Outcome Measure Data

Analysis Population Description

Participants with available data were included in the analysis.

Arm/Group Title	Probiotic Dietary Supplement	Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14	Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
Measure Participants	113	116
Median (Inter-Quartile Range) [days]	2	2

Adverse Events

Time Frame	From enrollment up to 6 weeks following delivery.
Arm/Group Title	Probiotic Dietary Supplement		Placebo
Arm/Group Description	Probiotic dietary supplement one capsule once per day until delivery. Probiotic dietary supplement: Dietary Supplement: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC -14		Placebo capsule, one daily until delivery. Placebo: One placebo capsule daily.
All Cause Mortality
	Probiotic Dietary Supplement		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/125 (0%)		0/126 (0%)
Serious Adverse Events
	Probiotic Dietary Supplement		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/125 (0.8%)		0/126 (0%)
Pregnancy, puerperium and perinatal conditions
Any other anticipated or unanticipated life-threatening event:intra-uterine fetal growth restriction	1/125 (0.8%)		0/126 (0%)
Other (Not Including Serious) Adverse Events
	Probiotic Dietary Supplement		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/125 (0%)		0/126 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.