Single Vs Multi-strain Probiotics for Preterm Neonates

Evaluation of the Clinical and Growth-related Effects of Probiotics in Preterm Infants: A Randomized, Placebo Controlled Clinical Trial.

The goal of this randomized control clinical trial is to determine if probiotics can prevent mortality and morbidity in preterm neonates. It also evaluates effects of probiotics on feeding pattern and growth. It will also learn about the comparative effects of single vs multiple strain probiotics.

It aims to answer:

Does probiotics improve the health and growth outcomes in preterm neonates in our population? Does single vs multiple strain of probiotics have difference in effects?

Participants will:

Participants given either single strain or multiple strain probiotics for 28 days post birth.

Data about mortality, morbidity, feeding pattern and growth (weight, height, head circumference gain) recorded on daily basis.

Study Overview

• Status: Completed
• Conditions: Growth; Feeding Intolerance; Necrotizing Enterocolitis of Newborn; Sepsis Newborn
• Intervention / Treatment: Dietary supplement: Dextrose 10%; Drug: Lactobacillus Rhamnosus GG; Drug: Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4

Detailed Description

This trial is single-centered, parallel, multi-arm, 1:1:1 randomized, blinded, placebo controlled clinical trial. It compares 3 groups; Group P1 (Placebo), Group P2-Single Strain probiotic (Lactobacillus rhamnosus GG) and Group P3- Multiple strains probiotic ( Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4) for preventing preterm neonatal morbidities, improving feeding tolerance and overall growth.

Primary objective: The primary objective of our trial will be to compare the incidence and severity of Necrotizing enterocolitis (NEC) from the time of trial participation till the end of trial treatment (28 days) according to Bell's grading criteria.

Secondary objectives:

All these outcomes will be measured from the day intervention started to the end of supplementation (28 days)

• To evaluate incidence of sepsis, intracerebral haemorrhage and periventricular leukomalacia, retinopathy of prematurity and bronchopulmonary dysplasia)
• To estimate the time to full enteral feeding (i.e., ≥150 ml/kg/day) and feeding tolerance based on Davy's Neonatal Feeding Assessment Scale (NFAS).
• To determine the effect of probiotics on growth (weight, height, and head circumference) of premature babies
• To assess comparative efficacy of single strain vs combination probiotics for aforementioned objectives

Framework/hypothesis: The experimental group P2 (Lactobacillus rhamnosus GG) and Group P3- ( Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4) are superior to control group (Placebo) as preventing NEC and other morbidities in preterm neonates, thus improving feeding tolerance and overall growth.

• Study Type: Interventional
• Enrollment (Actual): 249
• Phase: Phase 4

Contacts and Locations

Study Locations

• Pakistan
  • Punjab Province
    • Bahawalpur, Punjab Province, Pakistan, 62100
      • Bahawal Victoria Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Preterm babies of gestational age <35+6days, birth weight <2500 grams, received and tolerated at-least one feed within 72 hours of birth and informed consent from parents or guardian.

Exclusion Criteria:

• Neonates with major congenital malformations, gastrointestinal anomalies, early onset sepsis (C-reactive protein (CRP) >10 mg/L in the first 72 h of life) and renal insufficiency

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: P1; 1 ml of 10% dextrose water will be dispensed in 5cc syringe and administered orally or via feeding tube for 28 days.	Dietary supplement: Dextrose 10%; P1; Other Names: Placebo
Active Comparator: P2; Single strain probiotic- Lactobacillus rhamnosus GG. The single dose 1.5×109 CFU/day as 1 mL of the reconstituted solution will be given every day via the feeding tube or orally as applicable until reaching feeds of 50 mL/kg/day. It will be increased thereafter to 3×109 CFU/day once feeds exceed 50mL/kg/day.	Drug: Lactobacillus Rhamnosus GG; Single Strain; Other Names: Prepro GG
Active Comparator: P3; Multiple strain probiotic-Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4. The single dose 1.5×109 CFU/day as 1 mL of the reconstituted solution will be given every day via the feeding tube or orally as applicable until reaching feeds of 50 mL/kg/day. It will be increased thereafter to 3×109 CFU/day once feeds exceed 50mL/kg/day.	Drug: Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4; Multiple Strain; Other Names: Amybact

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Necrotizing enterocolitis (NEC)	Bell's classification used for grading and diagnosis	From the day intervention started to day 28 of supplementation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neonatal Sepsis	Clinical sepsis is defined as condition with at least two signs of systemic inflammatory response (e.g. temperature >38 C or <36.5 C, tachycardia > 200/min etc.), one laboratory sign (e.g. C-reactive protein >20mg/L) but no proof of causative agent in blood culture. Clinical sepsis with proof of blood culture positive for causative agent was defined as confirmed sepsis.	From the day intervention started to day 28 of supplementation
Feeding Intolerance	A gastrointestinal tolerance score, based on gastric residual volume, emesis, abdominal distension, number of stools and nil per oral days was calculated to identify and score feeding intolerance. Each score as 1. A score of >2 was considered gastric intolerance.	From the day intervention started to day 28 of supplementation
Weight	Weight measured in grams	From the day intervention started to day 28 of supplementation
Body length	Measured in millimeters daily once	From the day intervention started to day 28 of supplementation
Head Circumference	Measured in millimeters	From the day study started to day 28 of supplementation

Collaborators and Investigators

• Sponsor: Madiha, MPhil
• Investigators: Principal Investigator: Imran Masood, PhD, The Islamia University of Bahawalpur, Khawaja Fareed Campus

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2023
• Primary Completion (Actual): November 15, 2023
• Study Completion (Actual): October 15, 2025

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: December 8, 2025
• First Posted (Actual): December 22, 2025

Study Record Updates

• Last Update Posted (Actual): December 22, 2025
• Last Update Submitted That Met QC Criteria: December 8, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Probiotics; Preterm neonates; Single vs Multiple strain
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Neonatal Sepsis
• Other Study ID Numbers: NEOPRO-SvsM

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