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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pregnancy

Intervention / Treatment
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* Dietary Supplement: Probiotic
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic<br>Combination of two probiotic strains in one capsule | Dietary Supplement: Probiotic<br>* Dosing regimen of one capsule daily for a maximum of 18 weeks<br>|
| Placebo Comparator: Placebo<br>Non active ingredients in a capsule | Other: Placebo<br>* Dosing regimen of one capsule daily for a maximum of 18 weeks<br>|

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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probiotics, infections, bacterial vaginosis