Preventive Effect of Perinatal Oral Probiotic Supplementation (POPS) on Neonatal Jaundice: A Randomized Double-Blind Placebo-Controlled Parallel-Group Superiority Clinical Trial
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 94
- Locations
- 1
- Primary Endpoint
- Hyperbilirubinemia
Study Overview
Brief Summary
This is a randomized double-blind placebo-controlled parallel group superiority clinical trial among 94 pregnant women (47 in each group) to investigate the effect of maternal perinatal probiotic supplementation on neonatal jaundice, breast milk microbiome, maternal stool, and infant fecal microbiome. Vivomixx®-probiotic product will be used as treatment and placebo as a control.
Detailed Description
Neonatal jaundice is a yellowish discoloration of the skin and sclera because of over-concentration of circulating unconjugated bilirubin (hyperbilirubinemia) in the body. It can lead the baby to severe complications including death. Intestinal flora modulation by probiotics administration to the mother may tackle this problem. Therefore, investigators designed a randomized double-blind placebo-controlled parallel group superiority clinical trial among 94 pregnant women (47 in each group). Eligible pregnant women will be recruited voluntarily at 28-36 weeks of gestation and allocated randomly to either the probiotic group (Vivomixx®) or placebo group (maltose-containing unit) which are phenotypically similar. Participants will take one sachet of the product per day starting from 36 weeks of gestation until the end of first week of postpartum. Biological samples (maternal stool, breast milk, and neonatal faeces) will be collected at different time points. Additionally, neonatal transcutaneous bilirubin will be measured on the second and seventh day of life using a Drager Meter (a transcutaneous bilirubinometer). The microbial DNA will be extracted from biological samples using commercial kits and metagenomics sequencing will be employed and will be correlated with bilirubin level using appropriate statistical methods. This study will be conducted based on the Helsinki Declaration and International Council for Harmonization Requirements for Pharmaceuticals for Human Use (ICH) Guideline for Good Clinical Practice (GCP) standards. Ethical approval is obtained from the Joint Chinese University of Hong Kong and New Territories East Cluster (CUHK-NTEC) Clinical Research Ethics Committee, Hong Kong with reference number: 2023.100-T. Written informed consent will be obtained from each participant during enrolment.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
It is a double-blind study
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •All pregnant women aged 18-45 years old.
- •Gestational age of 28-34 weeks
- •Normal singleton pregnancy
Exclusion Criteria
- •Foetal abnormality
- •Mothers with antibiotic medication during the allocation
- •Couples with glucose 6-phosphate dehydrogenase enzyme deficiency
- •Couples with known rhesus or haemolytic disease history
- •Plan of place of birth at other hospitals other than Prince of Wales Hospital
- •known breast disorder or any contraindication for breastfeeding.
Arms & Interventions
Probiotics
Vivomixx® is a multi-strain probiotics product.
Intervention: Vivomixx® (Dietary Supplement)
Placebo
Maltose-containing placebo product
Intervention: Placebo (Dietary Supplement)
Outcomes
Primary Outcomes
Hyperbilirubinemia
Time Frame: 1 week since birth
Investigators will measure the transcutaneous bilirubin level on the second and seventh day of life and plot the record on the nomograph. The record above the 95th percentile will be taken as considerable hyperbilirubinemia and then the baby will be investigated for total serum bilirubin measurement if needed to declare hyperbilirubinemia. The outcome will be classified as hyperbilirubinemia and non-hyperbilirubinemia.
Transcutaneous bilirubin level
Time Frame: 1 week of life (after birth)
Infant's skin bilirubin level on the chest measured using a non-invasive devise called Drager meter. It will be measured in milligram per decilitre or micromole per liter. This outcome will be measured as a continuous outcome.
Secondary Outcomes
- Number of participants with Initiation of labor(within two days of birth)
- Birth weight(within two days of birth)
- Apgar scores(within two days of birth)
- Breast milk microbiome profile(From birth seventh day of postpartum)
- Preterm birth(within two days of birth)
- Mode of birth checklist(within two days of birth)
- Stool microbiome profile(From birth seventh day of postpartum)
Investigators
Ronald Wang
Professor
Chinese University of Hong Kong