The Efficacy of Probiotics to Reduce Antepartum Group B Streptococcus Colonization.

NCT ID: NCT03696953

Last Updated: 2024-03-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 109 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-01
• Study Completion Date: 2024-09-30

Brief Summary

This study is a randomized double blind, placebo controlled trial to determine the efficacy of an oral probiotic in reducing antenatal Group B Streptococcus colonization. The goal of this study is to demonstrate that women in the probiotics group will experience; (1) reduced GBS prenatal colonization at 36± 2 weeks gestation and lower levels of GBS colonization, (2) less need for intrapartum antibiotic prophylaxis and (3) fewer prenatal gastrointestinal symptoms compared to women in the placebo group.

Intrapartum measures were added and IRB approved in Feb 2020 as a pilot and feasibility substudy. The goals of this study are as follows: (1) Explore the effect of antepartum exposure to Florajen3 on maternal and neonatal residual GBS and the maternal microbiome. We anticipate that (1)At the time of labor, more women in the probiotics group will test negative for GBS on vaginal to rectal swabs compared to those in the placebo group and (2) Fewer neonates born to women in the probiotic group will have GBS on nasal-oral pharynx cultures within several hours of birth compared to those born to neonates in the control group.

Detailed Description

Group B streptococcus (GBS) is the most prevalent cause of perinatal infection, with mortality and profound comorbidities for neonates. Vaginal and gastrointestinal (GI) colonization with GBS occurs in up to 30% of adult women, with highest rates in African Americans. Pregnant women can pass GBS to their fetuses during vaginal birth, putting them at risk for Early Onset Group B Streptococcus Disease (EOGBSD), which is associated with a neonatal mortality rate of 5-10% and morbidity of approximately 50%. The Centers for Disease Control and Prevention (CDC) 2010 guidelines require universal antepartum GBS screening by vaginal to rectal cultures of all women at 35-37 weeks gestation, and intravenously administered intrapartum antibiotic prophylaxis (IAP) of two or more doses if a woman is found to be colonized with GBS. While use of these guidelines has significantly reduced EOGBSD incidence from 1.7 per 1,000 live births to 0.34-0.37, up to 30% of laboring women and their fetuses are exposed to IAP. Complications associated with IAP are significant for both the mother (increased incidence of antibiotic resistance, allergic sensitization, diarrhea including Clostridium difficile, and fungal infections) and neonate (gut dysbiosis, opportunistic infections, and allergic risk). The proposed study will test a low-cost, safe, innovative approach to reduce prenatal colonization with GBS, while adhering to CDC guidelines for EOGBSD prevention. Investigators hypothesize that women who ingest a commercially available oral probiotic combination product (Florajen3, containing Lactobacillus acidophilus, Bifidobacterium lactis, and Bifidobacterium longum) daily from 28 weeks gestation through the time of labor will have a lower risk of GBS colonization compared to women taking placebo. The purpose of this Phase 2 placebo-controlled, double blind, randomized controlled trial (RCT) is to determine the efficacy of once daily ingestion of Florajen3 by healthy low-risk pregnant women from 28 weeks gestation until the time of labor to (a) reduce the proportion of women with GBS colonization and thus (b) reduce the number of women who receive IAP. Investigators expect this intervention to alter the vaginal and rectal microbiota by (c) increasing Lactobacillus colony counts, (d) decreasing GBS colony counts, and (e) reducing GI symptoms. In preparation for this RCT, the research team conducted two preliminary studies (one in vitro, one in vivo), an integrative review of the literature regarding the use of prenatal probiotics, and a systematic review on probiotics and urogynecologic infections. The literature and preliminary work support the safety, tolerability, and potentially high impact of the oral probiotic as an innovative, low-risk, easy-to-use intervention to reduce GBS colonization during pregnancy and significantly reduce exposure of mothers and infants to IAP and the associated complications. If positive, findings from this study will shift the paradigm in clinical practice and be used to design and conduct a larger RCT to extend the science of nursing, midwifery, obstetrics, microbiology, clinical nutrition, and infectious disease for care of pregnant women and their infants.

Approximately 10% of women who tested negative for GBS at 36 weeks will become positive at the time of labor and birth. This "residual GBS" may be responsible for cases of EOGBSD cases.

Conditions

Group B Streptococcus Carrier in Childbirth; Gastrointestinal Symptoms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Probiotic

Florajen3 Combination Probiotic Product 15 billion CFU per capsule

1 capsule daily from 28 weeks until the time of birth.

Group Type: EXPERIMENTAL

Florajen3

Intervention Type: BIOLOGICAL

Probiotic combination product One capsule daily by mouth.

Placebo

Microcrystalline Cellulose

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Florajen3

Probiotic combination product One capsule daily by mouth.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Healthy adult (≥ 18 years of age) pregnant women who are 28±2 weeks gestation at enrollment [calculated from the first day of Last Normal Menstrual Period (LNMP) and/or ultrasound (US)]
• With: No obstetric complication* (e.g., pre-eclampsia, gestational diabetes, multiple gestation)
• No fetal complication (e.g., birth defect, intrauterine growth restriction)
• No medical complication (e.g., hypertension, diabetes mellitus)
• Who do not currently ingest an over the counter probiotic supplement (not including yogurt)
• Who can both speak and read English
• Who regularly attend prenatal care (defined as not > 1 prior missed appointment during this pregnancy)
• No Hypersensitivity reaction to β-lactam antibiotics

Exclusion Criteria

• Those less than 18 years of age
• Non-pregnant women
• Later in pregnancy than 30 weeks gestation at enrollment [per LNMP and/or US]
• Those with an obstetric, fetal or medical complication of pregnancy
• Pregnant women who have a history of GBS bacteriuria during the current pregnancy or have previously given birth to a GBS affected child
• Women who are currently ingesting an over the counter probiotic supplement (except for yogurt)
• Women who are planning an elective repeat cesarean birth
• Women who do not speak and read English
• Women with a history of missing more than one scheduled prenatal visit during this pregnancy
• Hypersensitivity reaction to β-lactam antibiotics

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Wake Forest University Health Sciences

OTHER

Sponsor Role: collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role: collaborator

Marquette University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lisa C Hanson, PhD

Role: PRINCIPAL_INVESTIGATOR

Marquette University, College of Nursing

Locations

Aurora Sinai Medical Center

Milwaukee, Wisconsin, United States

Countries

United States

References

Hanson L, Vandevusse L, Duster M, Warrack S, Safdar N. Feasibility of oral prenatal probiotics against maternal group B Streptococcus vaginal and rectal colonization. J Obstet Gynecol Neonatal Nurs. 2014 May-Jun;43(3):294-304. doi: 10.1111/1552-6909.12308. Epub 2014 Apr 22.

Reference Type: BACKGROUND

PMID: 24754328 (View on PubMed)

Hanson L, VandeVusse L, Jerme M, Abad CL, Safdar N. Probiotics for Treatment and Prevention of Urogenital Infections in Women: A Systematic Review. J Midwifery Womens Health. 2016 May;61(3):339-55. doi: 10.1111/jmwh.12472.

Reference Type: BACKGROUND

PMID: 27218592 (View on PubMed)

VandeVusse L, Hanson L, Safdar N. Perinatal outcomes of prenatal probiotic and prebiotic administration: an integrative review. J Perinat Neonatal Nurs. 2013 Oct-Dec;27(4):288-301; quiz E1-2. doi: 10.1097/JPN.0b013e3182a1e15d.

Reference Type: BACKGROUND

PMID: 24164813 (View on PubMed)

Hanson L, Vandevusse L. Probiotics are food; herbs are plants; what's the risk? Informed consent for complementary and integrative therapies. J Perinat Neonatal Nurs. 2010 Jul-Sep;24(3):201-4. doi: 10.1097/JPN.0b013e3181e8f930. No abstract available.

Reference Type: BACKGROUND

PMID: 20697235 (View on PubMed)

Dunn AB, Hanson L, VandeVusse L, Leslie S. Through the Microbial Looking Glass: Premature Labor, Preeclampsia, and Gestational Diabetes: A Scoping Review. J Perinat Neonatal Nurs. 2019 Jan/Mar;33(1):35-51. doi: 10.1097/JPN.0000000000000375.

Reference Type: BACKGROUND

PMID: 30676461 (View on PubMed)

Simonson J, Haglund K, Weber E, Fial A, Hanson L. Probiotics for the Management of Infantile Colic: A Systematic Review. MCN Am J Matern Child Nurs. 2021 Mar-Apr 01;46(2):88-96. doi: 10.1097/NMC.0000000000000691.

Reference Type: BACKGROUND

PMID: 33315632 (View on PubMed)

Malloy E, Kates A, Watson L, VandeVusse L, Safdar N, Hanson L. Laboratory Analysis Techniques for the Perinatal Microbiome: Implications for Studies of Probiotic Interventions. J Perinat Neonatal Nurs. 2020 Jul/Sep;34(3):239-250. doi: 10.1097/JPN.0000000000000496.

Reference Type: BACKGROUND

PMID: 32697544 (View on PubMed)

Hanson L, VandeVusse L, Forgie M, Malloy E, Singh M, Scherer M, Kleber D, Dixon J, Hryckowian AJ, Safdar N. A randomized controlled trial of an oral probiotic to reduce antepartum group B Streptococcus colonization and gastrointestinal symptoms. Am J Obstet Gynecol MFM. 2023 Jan;5(1):100748. doi: 10.1016/j.ajogmf.2022.100748. Epub 2022 Sep 13.

Reference Type: RESULT

PMID: 36108911 (View on PubMed)

Hanson L, Albert K, Malloy E, Singh M, Kallay M, Brandt A, Morris C, Kleber D, Forgie M. Participant Personal Characteristics and Adherence to Oral Capsules: A Secondary Analysis of a Randomized Placebo-Controlled Trial of Antenatal Probiotics. J Midwifery Womens Health. 2025 May-Jun;70(3):452-459. doi: 10.1111/jmwh.13686. Epub 2024 Oct 1.

Reference Type: DERIVED

PMID: 39351987 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R21HD095320

Identifier Type: NIH

Identifier Source: org_study_id

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