The Effect of Probiotics on Maintenance of Health in Pregnancy and Infants

The Effect of Probiotics on Maintenance of Health in Pregnancy and Infants: a Randomized, Double-blind, Placebo Controlled Study

This phase 2 study evaluates the effect of perinatal use of probiotics on the number of diagnosed viral, bacterial and fungal infections in pregnant women and on the maintenance of a health pregnancy. In addition, the effect of probiotics intake during pregnancy and breastfeeding on the infant's overall health status will be evaluated.

Study Overview

• Status: Completed
• Conditions: Pregnancy
• Intervention / Treatment: Dietary supplement: Probiotic; Other: Placebo

Detailed Description

Throughout pregnancy women undergo many biological changes, including alterations in their microbiota. These infections can exacerbate pregnancy complications and increase the risk of preeclampsia and preterm birth. The present study aims to evaluate the potential effects of perinatal use of probiotics on the number of diagnosed viral, bacterial and fungal infections in pregnant women and on the maintenance of a healthy pregnancy. Potential infections include but are not limited to influenza/colds, bacterial vaginosis, mastitis, candidiasis, urinary tract infection and gingivitis. Additionally, the benefits of probiotic intake by the mother on the infant during pregnancy and breastfeeding will be evaluated.

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada
      • Clinique OVO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Healthy pregnant women
• Less than 28 weeks of gestation (3rd trimester)
• ≥18 to <40 years old
• Singleton gestation
• Availability and willingness to come in for morning visits
• Planning to breastfeed
• Willing to complete questionnaires, records, and diaries associated with the study and to complete all clinical visits
• Willing to discontinue consumption of fermented foods (e.g. foods that contain probiotics such as Kefir, pickles, etc.) or probiotics (e.g. yogurts with live active cultures or probiotic supplements)
• Able to provide informed consent

Exclusion Criteria:

• Known gestational diabetes or diabetes type 1 or 2
• Known blood/bleeding disorders
• Known liver and kidney disorders
• Known unstable cardiovascular diseases
• Women with a personal history of or currently diagnosed with preeclampsia
• Suffering from neurological diseases (e.g. Alzheimer's disease, Parkinson's disease, epilepsy, etc.)
• Suffering from gastrointestinal diseases (e.g. gastric ulcers, Crohn's disease, ulcerative colitis, etc.)
• Current symptoms of depression or experienced depressive symptoms in the past 2 years
• Maternal history of second trimester loss
• Women diagnosed HIV Positive or with Hepatitis B or C
• Known fetal abnormality
• Daily use of probiotic product within 2 weeks of the screening visit. The potential participant could be eligible to participate after a 2-week wash-out period
• Use of any antibiotic drug within 1 month of screening. The potential participant could be eligible to participate after a 2-week wash-out period
• Smoking, alcohol consumption or drug use during pregnancy
• History of alcohol or substance abuse six months prior to screening
• Allergies to milk, soy, or yeast

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Probiotic; Combination of two probiotic strains in one capsule	Dietary supplement: Probiotic; Dosing regimen of one capsule daily for a maximum of 18 weeks
PLACEBO_COMPARATOR: Placebo; Non active ingredients in a capsule	Other: Placebo; Dosing regimen of one capsule daily for a maximum of 18 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of diagnosed infections in pregnant women	This includes any viral, bacterial and fungal infection (e.g. bacterial vaginosis, candidiasis, urinary tract infection, mastitis, cold, flu, gingivitis, etc.). A vaginal swab and saliva sample will be taken at every visit on site throughout pregnancy. The vaginal swab will be used for the detection of Bacterial Vaginosis and Candidiasis. Other required swab samples will be collected if an infection occurs (e.g. vaginal, mouth, throat, nose, etc.). If an infection is suspected by a participant in-between a scheduled visit, the participant will come on site to be checked by a doctor. If the participant is subsequently diagnosed with an infection, a saliva sample will need to be taken at this time.	up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of glucose, insulin, triglycerides and iron	Assessed via blood sample throughout the pregnancy	Measured 2 times up to 12 weeks
Vaginal mycobiota	Vaginal microbiome which includes bacteria, fungus and potentially other eukaryotic micro-organisms such as parasites or viruses. To be assessed with a vaginal swab during pregnancy and after delivery.	Measured 3 times up to 18 weeks
Inflammatory markers	Assessing levels of both pro- and anti- inflammatory markers in the mother during pregnancy (through stool and blood samples) and after delivery (through breast milk sample).	Measured up to 3 times in the 18 week time frame
Vaginal microbiota	Effects of the probiotic interventions on overall microbiota composition in the mother will be assessed. In addition, recovery of the probiotic strains in the vaginal samples will be assessed.	Measured 3 times up to 18 weeks
Premature rupture of membranes (PROM)	Incidence of PROM on the probiotic versus the group	Measured 1 time at week 12
Levels of secretory immunoglobulin A (sIgA) in the mother	Assessed via saliva samples throughout pregnancy and a breast milk sample after delivery.	Measured up to 4 times in the 18 week time frame
Levels of secretory immunoglobulin A (sIgA) in the infant	Assessed via stool sample after birth.	Measured 1 time up to18 weeks
Gut microbiota in the mother	Effects of the probiotic interventions on overall microbiota composition will be assessed. In addition, recovery of the probiotic strains in the stool samples will be assessed.	Measured 3 times up to 18 weeks
Gut microbiota in the infant	Effects of the probiotic interventions on overall microbiota composition will be assessed. In addition, recovery of the probiotic strains in the stool samples will be assessed.	Measured 1 time up to 18 weeks
Stool frequency and consistency in the mother	Assessed with the Bristol Stool Scale	Self-reported, daily up to 18 weeks
Stool frequency and pattern in the infant	Assessed with the Amsterdam Infant Stool Scale	Self-reported by the mother, daily up to 4-6 weeks
Weight in the mother	To assess change in body weight	Measured 3 times up to 18 weeks. Pre-pregnancy weight will also be noted via information collection on a demographic questionnaire.
Breast milk microbiota	Effects of the probiotic interventions on overall microbiota composition will be assessed. In addition, recovery of the probiotic strains in the breast milk samples will be assessed.	Measured 1 time up to 18 weeks
Post-Partum Depression	To be assessed with the Edinburgh Postnatal Depression Scale	Measured 2 time up to 18 weeks
Infant's health status - NEC	To assess the probability of an infant with NEC	Measured 1 time up to 18 weeks.
Anthropometric measurements	Crown-heel length and head circumference	Measured 1 time up to 18 weeks. The infant's anthropometric measurements at birth will also be noted.
Weight in the infant	To assess change in body weight	Measured 2 times up to 18 weeks.
Crying time in the infant	To assess the mean daily crying time of infants	Self-reported by the mother, daily up to 4-6 weeks
Colic in the infant	To asses the probability of an infant with colic	Self-reported by the mother, daily up to 4-6 weeks
Sleep in the infant	Number of total hours and number of consecutive hours	Self-reported by the mother, daily up to 4-6 weeks
Number of infections	To assess the number of infections	Self-reported by the mother, daily up to 4-6 weeks
Skin diseases or conditions	Skin diseases/conditions as well as the child's overall health status 1 year after birth will be assessed.	1 year follow up phone call
Infant's health status - jaundice	To assess the probability of an infant with jaundice	Measured 1 time up to 18 weeks.
Infant's health status - Hyperbilirubinemia	To assess the probability of an infant with Hyperbilirubinemia	Measured 1 time up to 18 weeks.

Collaborators and Investigators

• Sponsor: Lallemand Health Solutions
• Collaborators: Clinique Ovo

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 23, 2017
• Primary Completion (ACTUAL): May 20, 2022
• Study Completion (ACTUAL): May 20, 2022

Study Registration Dates

• First Submitted: September 28, 2017
• First Submitted That Met QC Criteria: October 13, 2017
• First Posted (ACTUAL): October 16, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 2, 2023
• Last Update Submitted That Met QC Criteria: February 1, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: probiotics; infections; bacterial vaginosis
• Other Study ID Numbers: MOM study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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