A Double-Blind Randomized Control Trial of a Synbiotic vs. Placebo Among Pregnant Women to Evaluate Colonization of the Gut Microbiota of Their Infants with Lactobacillus Plantarum (Probiotics Pilot in Ghana).

January 10, 2025 | Ongoing Project | Reading time: 8 min

Introduction

KHRC is conducting this study to investigate how probiotics given to pregnant women can improve the gut (digestive system) health of their babies and reduce the risk of infections during early life. The study focuses on pregnant women and their infants, aiming to understand how a specific probiotic strain named Lactobacillus plantarum, taken during pregnancy influence the microorganisms that live in the digestive tract of babies. This study could help address serious health challenges faced by newborns, including infections that claim over 1 million infant lives annually.

Investigators

Dr. John Amoah, Dr. Dennis Adu-Gyasi, Dr. Kaali Seyram, Miss Irene Azindow, and Mr. Ato Wilson.

Background

The newborn stage is the most vulnerable period in a person’s life, with the highest life-time risk of invasive infections. Globally, more than 1 million infants lose their lives to infections each year. Unfortunately, there are currently no effective solutions to reduce preterm births (PTB) or significantly reduce infection-related illnesses and deaths in newborns. the only strategies in place to prevent infectious morbidity and mortality in newborns are limited to the promotion of clean birth, skin-to-skin contact, and exclusive breastfeeding during the neonatal period. exclusive breastfeeding in the newborn period. Other medical interventions include the administeration of vitamin K and antibiotic eye drops at birth.

Recent research has shown promise in using probiotics during pregnancy to lower the risk of PTB. Recent clinical trials in low- and middle-income countries have also demonstrated that neonatal probiotic supplementation can significantly reduce neonatal and early infant infection rates, with excellent safety outcomes and no reported adverse effects.

This study therefore aims to evaluate how well probiotics taken during pregnancy can colonize the gut microbiome of infants. By supplementing pregnant women in their fifth to sixth month, this pilot study will afford us the opportunity to explore the impact of probiotic supplementation on birth outcomes and pave the way for improved maternal and child health strategies.

Objectives

Primary Objective

The study seeks to conduct a pilot trial to evaluate the effectiveness of administering probiotic supplements to pregnant women in their fifth to sixth month of pregnancy and assess how effective these probiotics colonize the gut microbiome of their infants by one month after birth.

Secondary Objective

1. To assess the compliance of pregnant women to a symbiotic product (Lp + FOS) during the study period.

2. To assess whether maternal and infant stool microbiomes can serve as indicators for predicting preterm birth (PTB) and/or possible serious bacterial infections (pSBI) in newborns.

3. To assess if maternal stool microbiome profoundly changes from immediately after childbirth to one month postpartum.

4. To characterize the diversity of vaginal microbiomes among pregnant women in the study area.

5. To determine the safety of administering probiotic supplementation to pregnant women from their fifth to sixth month of pregnancy until up to two weeks postpartum.

Methodology

This study is a prospective, randomized, double-blinded, placebo-controlled design. Pregnant women in their fifth to sixth months of pregnancy from the Kintampo North Municipality and South District were enrolled in the study after providing informed consent. Participants were randomly assigned, using computer-assisted programmes, to receive either a daily synbiotic supplement (Lp + FOS) or a placebo throughout the rest of their pregnancies and up to two weeks postpartum. Weekly probiotic supplementation also began upon enrolment, with follow-up assessments conducted one month after delivery.

To ensure proper administration of the supplement, participants received pictorial instructional materials. They also receive guidance from the study team to take two capsules with water every morning within one hour of waking-up, avoiding solid food or beverages other than water. The study team supervised the initial dose on-site and monitored adherence throughout the study. The supplements were checked weekly, and the pills were resupplied as needed.

Data on participants' demographic details, physical measurements, and health records were collected over the study period. Participants received standard medical care when unwell during the trial. Biological samples, including vaginal swabs (where possible), stool samples from mothers and infants, and breast milk were also collected at predetermined intervals for molecular analysis. Each participant of the study exited after one month postpartum. However, at the end of the study, all newborns exposed to the study intervention will receive follow-up care for one year under by a study paediatrician to monitor their health.

Expected Outcomes

This study hopes to achieve the following outcomes.

1. Identify the presence of probiotic strains in the gut microbiota of infants one month after birth, whose mothers received probiotic supplementation during pregnancy.

2. The level of compliance in the administration of the probiotic supplement among pregnant women.

3. Comparison of birth outcomes between participants who received the probiotic supplement and those who were given a placebo.

4. Gain Insights into the relationship between maternal and newborn gut microbiomes and their potential impact on infant health or susceptibility to infections.

5. Analysis of the diversity of vaginal microbiomes among pregnant women in the study region.

6. Collection of essential birth-related clinical data, including the length of labor, duration of membrane rupture, and use of prenatal antibiotics.

7. Exploration of the relationship between maternal and infant gut microbiomes, newborn illnesses, and the prevalence of bacteria among healthy mother-infant pairs.

8. Understanding the influence of maternal factors, such as pregnancy stage, postpartum period, and diet, on stool and breastmilk microbial communities.

Funder

Kintampo Health Research Centre (KHRC).

Collaborators

Dr. Nelly Amenyogbe, Prof. Tobias R. Kollman, and Prof. Pinaki Panigrahi.

Conclusion

This study is an important step to understand how probiotics can address some of the biggest challenges in maternal and child health. By focusing on simple, safe, and accessible interventions, the research could offer hope to families in Ghana and other low- and middle-income countries.