Validation of the In-utero Transmission of Probiotics (PROBIO)

Validation of the In-utero Transmission of Probiotics From the Mother to the Baby: A Randomized Crossover Pilot Study

This pilot project aims at confirming the in-utero transmission of probiotics, from the mother to the baby. Women aged 18 to 42 years, with a single pregnancy, considered low risk will be approached for this study. Women will take the investigational products between 34 weeks of pregnancy up to 10 days post-partum. Investigational products are probiotics (5 bacterial strains) compared to placebo.

Study Overview

• Status: Completed
• Conditions: In Utero Drug Exposure
• Intervention / Treatment: Biological: Natural products: Probiotics; Other: Placebo

Detailed Description

Rational: Studies have shown that probiotics given to babies can reduce perinatal complications. A change of practice should therefore be introduced in the management of premature newborns. However, one could assume that probiotic administration before birth could be as effective if not more. Indeed, one could hypothesise that when the newborn is exposed to probiotics earlier, the protective effect is potentially increased.

Objective: This pilot project aims at confirming the in-utero transmission of probiotics, from the mother to the baby.

Population: Women aged 18 to 42 years, with a single pregnancy, considered low risk will be approached for this study Products under study: Probiotics containing 5 bacterial strains (total of 12 million colony-forming unit / day) vs. Placebo.

Procedure: At 32-33 weeks, participants will complete questionnaires (medical, obstetrical, socio-demographic data) and will be randomized (double-blind) in one of the 2 following groups:

Group A: taking probiotics every day from the 34th week of pregnancy until delivery; taking placebo for 10 days after delivery.

Group B: taking placebo every day from the 34th week of pregnancy until delivery; taking probiotics for 10 days after delivery.

Follow-up: All women will complete a logbook to monitor the study products intake and monitor side effects until the end of the study (10 days postpartum).

Samples: maternal stool samples, vaginal secretions, stool (and meconium) as well as breast milk (and colostrum) will be taken at different times of the study to confirm the presence of probiotics and transmission between the mother and the baby.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amelie Tetu; Phone Number: 15571 8193461110; Email: amelie.tetu.ciussse-chus@ssss.gouv.qc.ca
• Study Contact Backup: Name: Audrey Hamel-Thibault; Phone Number: 12865 8193461110; Email: Audrey.Hamel-Thibault@USherbrooke.ca

Study Locations

• Canada
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • CIUSSS de l'Estrie-CHUS Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 42 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Women with a single pregnancy
• Women with a low risk pregnancy
• Women wishing to breastfeed at birth
• Women randomized between 32 0/7 - 33 6/7 weeks of gestation

Exclusion Criteria:

• History of obstetric complications (prematurity <37 weeks, preeclampsia , gestational diabetes treated with insulin)
• Obstetric or fetal complications known for current pregnancy such as threaten preterm labor (premature rupture of membranes or preterm labor), chorioamnionitis, placenta previa, active vaginal bleeding, cervical cerclage, fetal distress or anomalies, corticosteroid therapy
• Risk factors for obstetric complications during current pregnancy such as gestational diabetes, type I / II diabetes and high blood pressure (systole ≥140 and diastole ≥90)
• Antibiotic use within 2 weeks before randomisation
• Intake of probiotics or foods enriched with active cultures (fermented milk, kefir, kombucha ...) within 2 weeks before randomisation
• Women positive for Group B Streptococcus during previous pregnancies
• Weakened immune system (AIDS, lymphoma, chemoradiotherapy or corticotherapy, immunosuppressive pathology)
• Allergy or intolerance to lactose, soy or yeast.
• Women under Coumadin
• Women who plan to give birth outside the participating center
• Women who do not plan to breastfeed or extract their milk in the first 10 days after delivery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: prenatal probiotic; will take probiotics every day from the 34th week of pregnancy until delivery; taking placebo for 10 days after delivery	Biological: Natural products: Probiotics; Probiotics intake every day (1.5 gram) from 34 weeks of gestation to delivery OR from delivery to 10 days postpartum; Other: Placebo; Placebo intake every day (1.5 gram) from 34 weeks of gestation to delivery OR from delivery to 10 days postpartum
Active Comparator: postnatal probiotic; will take placebo every day from the 34th week of pregnancy until delivery; taking probiotics for 10 days after delivery	Biological: Natural products: Probiotics; Probiotics intake every day (1.5 gram) from 34 weeks of gestation to delivery OR from delivery to 10 days postpartum; Other: Placebo; Placebo intake every day (1.5 gram) from 34 weeks of gestation to delivery OR from delivery to 10 days postpartum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
in-utero transmission of probiotic	presence (yes or no) of probiotic (specific bacterial strains) in neonate meconium	at birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
transmission of probiotic to colostrum	presence(yes or no) of probiotic (specific bacterial strains) in colostrum	at birth
transmission of probiotic to maternal milk	presence (yes or no) of probiotic (specific bacterial strains) in breastmilk	10 days postpartum
transmission of probiotic to maternal vaginal tract	presence (yes or no) of probiotic (specific bacterial strains) in maternal vaginal swab	37 weeks of gestation
transmission of probiotic to maternal gut	presence (yes or no) of probiotic (specific bacterial strains) in maternal stools	37 weeks of gestation
postnatal transmission of probiotic to the neonate	presence (yes or no) of probiotic (specific bacterial strains) in neonate stools	10 days postpartum

Collaborators and Investigators

• Sponsor: Centre de recherche du Centre hospitalier universitaire de Sherbrooke
• Collaborators: Lallemand Health Solutions
• Investigators: Principal Investigator: Jean-Charles Pasquier, MD, CIUSSS-Estrie-CHUS hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2022
• Primary Completion (Actual): August 28, 2023
• Study Completion (Actual): November 28, 2023

Study Registration Dates

• First Submitted: August 5, 2019
• First Submitted That Met QC Criteria: August 6, 2019
• First Posted (Actual): August 8, 2019

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: probiotic; pilot study; in-utero transmission
• Other Study ID Numbers: 2020-3242

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is a pilot study. Samples and data will be used to confirm the principal hypothesis and explorative secondary objectives.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No