Preventive Effect of Perinatal Oral Probiotic Supplementation (POPS) on Neonatal Jaundice

Preventive Effect of Perinatal Oral Probiotic Supplementation (POPS) on Neonatal Jaundice: A Randomized Double-Blind Placebo-Controlled Parallel-Group Superiority Clinical Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Pregnancy Related; Microtia; Neonatal Jaundice
• Intervention / Treatment: Dietary supplement: Vivomixx®; Dietary supplement: Placebo

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 Type: Interventional
• Enrollment (Estimated): 94
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotics; Vivomixx® is a multi-strain probiotics product.	Dietary supplement: Vivomixx®; The probiotic group participants will receive 1 sachet of probiotic product daily from 36weeks of gestation up to 7th day of postpartum while placebo groups will 1 sachet placebo prepared with the same colour, taste, and packaging with Vivomixx® daily for the same duration of probiotic groups. Vivomixx® is a non-genetically modified (GMO), gluten-free, high potency microbiotic food supplement, containing eight strains (Streptococcus thermophilus DSM24731® / NCIMB 30438, Bifidobacterium breve DSM24732® / NCIMB 30441, Bifidobacterium longum DSM24736® / NCIMB 30435, Bifidobacterium infantis DSM24737® / NCIMB 30436*, Lactobacillus acidophilus DSM24735® / NCIMB 30442, Lactobacillus plantarum DSM24730® / NCIMB 30437, Lactobacillus paracasei DSM24733® / NCIMB 30439, Lactobacillus delbrueckii subsp. bulgaricus DSM24734® / NCIMB 30440) of live bacteria (450 billion bacteria per sachet).
Placebo Comparator: Placebo; Maltose-containing placebo product	Dietary supplement: Placebo; A maltose- containing product with a similar phenotype with Vivomixx®.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neonatal Jaundice	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 jaundice and then the physician in charge will declare the diagnosis by clinical evaluation and total serum bilirubin measurement if needed. The outcome will be classified as jaundiced or non-jaundice.	1 week since birth
Transcutaneous bilirubin level	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.	1 week of life (after birth)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preterm birth	This will be measured using the gestational age at birth	within two days of birth
Number of participants with Initiation of labor	Spontaneous initiation of induction of labour	within two days of birth
Mode of birth checklist	Spontaneous vaginal delivery, assisted birth or cesarean section	within two days of birth
Birth weight	Weight of the baby at birth in grams	within two days of birth
Apgar scores	First and fifth-minute Apgar scores of babies	within two days of birth
Breast milk microbiome profile	Breast milk samples will be collected, bacterial DNA collected and meta-genomic sequencing will be carried out.	From birth seventh day of postpartum
Stool microbiome profile	maternal and infant stool samples will be collected, bacterial DNA collected and meta-genomic sequencing will be carried out.	From birth seventh day of postpartum

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Skin rash	any allergic reaction	From initiation of the intervention until 1 week postpartum
Number of participants with Diarrhea	Frequent loose of stool	From initiation of the intervention until 1 week postpartum
Number of participants with Abdominal bloating	Any distention, gas (flatulence) and cramp on the abdomen	From initiation of the intervention until 1 week postpartum

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Publications and helpful links

Helpful Links

• Intervention product details.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: October 5, 2023
• First Submitted That Met QC Criteria: October 17, 2023
• First Posted (Actual): October 18, 2023

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Congenital Abnormalities; Infant, Newborn, Diseases; Otorhinolaryngologic Diseases; Ear Diseases; Skin Manifestations; Hyperbilirubinemia; Hyperbilirubinemia, Neonatal; Jaundice; Congenital Microtia; Jaundice, Neonatal
• Other Study ID Numbers: 20230317

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data will be included in publications of findings as a supplementary file. It will be available to anyone based on official request from the principal investigator.
• IPD Sharing Time Frame: One year after initiation of the study
• IPD Sharing Access Criteria: official request and memorandum of understanding signing
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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