Effect of Probiotic Lacobacillus Reuterii on Serum Bilirubin Levels in Preterm Infants

The goal of this clinical trial is to learn about the effect of probiotic Lactobacillus reuterii on the level of serum bilirubin in moderately and late preterm infants with birth weights 1000 grams to 2499 grams who were admitted to the NICU at Dr. Wahidin Sudirohusodo Hospital, Hasanuddin University Hospital and Cahaya Medika Hospital. The main questions it aims to answer are:

• Are bilirubin levels in preterm infants who received probiotics were lower than those who did not receive probiotics?
• Is the incidence of hyperbilirubinemia requiring phototherapy in preterm infants who received probiotics less than those who did not receive probiotics?

Study Overview

• Status: Completed
• Conditions: Hyperbilirubinemia, Neonatal
• Intervention / Treatment: Dietary supplement: Lactobacillus reuterii

Detailed Description

This study aims to investigate the effect of probiotic Lactobacillus reuteri administration on serum bilirubin levels in preterm infants. It is a randomized controlled trial conducted at the Neonatal Intensive Care Units of Dr. Wahidin Sudirohusodo Hospital, Hasanuddin University Hospital and Cahaya Medika Hospital in Makassar, South Sulawesi, Indonesia. The study population includes infants born at 32 to <37 weeks gestational age with birth weights between 1000-2499 grams who are admitted to the NICU. Eligible infants are randomized into two groups - an intervention group receiving probiotic L. reuteri (5 drops daily for 7 days) and a control group not receiving probiotics. The primary outcome is serum bilirubin levels, measured at baseline and after 7 days of intervention. Secondary outcomes include incidence of hyperbilirubinemia requiring phototherapy and changes in bilirubin levels in those receiving phototherapy. Blood samples are collected to measure total and direct bilirubin levels. The study aims to enroll 40 infants (20 per group) to detect a clinically meaningful difference in bilirubin levels between groups. This trial will provide evidence on whether probiotic supplementation with L. reuteri can reduce the severity of hyperbilirubinemia in preterm infants. The results may inform clinical practice regarding the use of probiotics as an adjunctive therapy for neonatal jaundice in this vulnerable population.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Indonesia
  • South Sulawesi
    • Makassar, South Sulawesi, Indonesia, 90245
      • Hasanuddin University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Premature Infants (32 - < 37 weeks gestation)
• Birth weight 1000 - 2499 grams
• Sick infants who are treated in the NICU
• Preterm infants who received enteral feeding > 30 cc/kgBB less than 72 hours after birth, without jaundice or jaundice Kremer 1,2, and 3
• Parents have signed their child's consent to participate in the study

Exclusion Criteria:

• Infants with multiple congenital abnormalities
• Infants with jaundice before 24 hours or having jaundice cremer > 4 less than 72 hours from birth
• Infants with Sepsis, Metabolic acidosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group; Preterm infants who receive 5 drops of probiotic Lactobacillus reuteri for 7 days	Dietary supplement: Lactobacillus reuterii; Participants in the intervention group received probiotic Lactobacillus reuterii if they received enteral feeding > 30 cc/kgBW. 5 drops of probiotics were given for 7 days in the breast milk or formula milk that did not contain probiotics
No Intervention: Control Group; Preterm infants who receive standard care without probiotics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total bilirubin level	We compare the total bilirubin level between participants who received probiotics and those who did not receive probiotics	Total bilirubin level was measured after 7th day of intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phototherapy	We compare the number of participants who needed phototherapy between probiotic and non-probiotic group	The need for phototherapy was assessed throughout the intervention (7 days)

Collaborators and Investigators

• Sponsor: Hasanuddin University
• Investigators: Principal Investigator: Nurwahyuni Rachim, MD, Hasanuddin University

Publications and helpful links

General Publications

• Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med. 2014 May 21;6(237):237ra65. doi: 10.1126/scitranslmed.3008599.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Actual): September 21, 2024
• Study Completion (Actual): October 21, 2024

Study Registration Dates

• First Submitted: October 30, 2024
• First Submitted That Met QC Criteria: October 31, 2024
• First Posted (Actual): November 4, 2024

Study Record Updates

• Last Update Posted (Estimated): November 26, 2024
• Last Update Submitted That Met QC Criteria: November 23, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: probiotic; hyperbilirubinemia; Lactobacillus reuterii
• Additional Relevant MeSH Terms: Pathologic Processes; Infant, Newborn, Diseases; Hyperbilirubinemia, Neonatal; Hyperbilirubinemia
• Other Study ID Numbers: UH105201003

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
• product manufactured in and exported from the U.S.: No