Probiotics Supplementation for Neurodevelopment in Preterm Infants

Official title

Effect of Gut Microbiota Remodeling Via Probiotics Supplementation on Neurodevelopment in Preterm Infants: A Randomized Controlled Trial

Overview

The purpose of this randomized controlled trial is to evaluate the effect of daily supplementation with a probiotic mixture on the neurodevelopmental outcomes of preterm infants with a history of neonatal antibiotic exposure. The intervention lasts for 6 months. The study hypothesizes that early gut microbiota remodeling via exogenous probiotics can improve neurodevelopment. The primary outcome is assessed by the Gesell Developmental Schedules or the Ages \& Stages Questionnaires (ASQ-3). Secondary outcomes include longitudinal changes in gut microbiota composition,targeted metabolomics (such as short-chain fatty acids \[SCFAs\], and systemic inflammatory markers.

Detailed description

Preterm infants frequently experience delayed or disrupted gut microbiota colonization due to perinatal complications and early-life antibiotic exposure in the Neonatal Intensive Care Unit (NICU). This early-life dysbiosis is increasingly recognized to impact brain development and increase the risk of neurodevelopmental delays through the microbiota-gut-brain axis.This single-blind, randomized controlled trial aims to investigate whether remodeling the gut microbiota via probiotic supplementation can improve neurodevelopmental trajectories. Eligible preterm infants (corrected age of 6 months ± 7days) with a history of neonatal antibiotic use will be randomized into either the probiotic intervention group or the standard care control group. The intervention group will receive a daily oral probiotic mixture containing Bifidobacterium animalis subsp. lactis Bb-12 and Lacticaseibacillus rhamnosus LGG at a dose of 3\*10\^9 Colony Forming Units per day (CFU/day) for 6 months.Clinical evaluations, including comprehensive growth monitoring and neurodevelopmental assessments (Gesell Developmental Schedules or ASQ-3), will be conducted. Fecal and blood samples will be systematically collected to analyze gut microbiota diversity and specific metabolic profiles. Specifically, targeted metabolomics will be employed to explore innovative host-microbe signaling. The findings will provide clinical evidence for using microbiota-targeted nutritional interventions to protect early neurodevelopment in vulnerable preterm populations.

Interventions

• Dietary supplement Probiotic Mixture (Bifidobacterium animalis subsp. lactis Bb-12 and Lacticaseibacillus rhamnosus LGG)
  Daily oral administration of a probiotic mixture containing Bifidobacterium animalis subsp. lactis Bb-12 and Lacticaseibacillus rhamnosus LGG at a dose of 3 x 10\^9 CFU/day for 6 months.

Primary outcome measures

• Mean Neurodevelopmental Assessment Score [Time frame: Baseline and 6 months post-intervention]

Secondary outcome measures (4)

• Change from Baseline in Gut Microbiota Alpha Diversity (Chao1 and Shannon Index Values) [Time frame: Baseline and 6 months post-intervention]
• Relative Abundance of Specific Gut Microbiota Taxa [Time frame: Baseline and 6 months post-intervention]
• Concentration of Fecal Short-Chain Fatty Acids (SCFAs) [Time frame: Baseline, 3 months and 6 months post-intervention]
• Concentration of Systemic Inflammatory Markers [Time frame: Baseline, 3 months and 6 months post-intervention]

Eligibility criteria

Inclusion criteria

• Preterm infants with a gestational age between 28 and 37 weeks (inclusive of 28 weeks)
• Documented history of neonatal intravenous antibiotic exposure for at least 5 consecutive days during the neonatal period (e.g., in the NICU).
• Corrected age of 6 months ± 7days at the time of enrollment.
• No systemic antibiotic usage within 14 days prior to screening.
• Legal guardians are willing to sign the informed consent form and comply with the 6-month intervention and follow-up schedule.

Exclusion criteria

• Severe congenital malformations, chromosomal abnormalities, or inherited metabolic diseases (e.g., Down syndrome).
• Severe neurological disorders or structural brain injuries (e.g., Grade III/IV intraventricular hemorrhage, cystic periventricular leukomalacia, or hydrocephalus requiring a shunt).
• Severe chronic diseases affecting growth and development (e.g., congenital heart disease requiring surgery, short bowel syndrome, or severe sequelae of necrotizing enterocolitis).
• Concurrent participation in other interventional clinical trials.
• Planned long-term use of other commercial probiotic/prebiotic supplements outside the study protocol during the intervention period.
• High risk of loss to follow-up (e.g., expected relocation).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

China · 1 center

• Shanghai Children's Hospital — Shanghai

Publications

• Kajzar F, Taliani C, Danieli R, Rossini S, Zamboni R. Dispersion of third-harmonic-generation optical susceptibility in C70 thin films. Phys Rev Lett. 1994 Sep 19;73(12):1617-1620. doi: 10.1103/PhysRevLett.73.1617. No abstract available. PMID 10056840
• FOXON GE. Cinematographic technique for amphibian blood circulation. Nature. 1953 May 2;171(4357):801-2. doi: 10.1038/172801b0. No abstract available. PMID 13054730
• Stenfelt S, Hakansson B, Jonsson R, Granstrom G. A bone-anchored hearing aid for patients with pure sensorineural hearing impairment: a pilot study. Scand Audiol. 2000;29(3):175-85. doi: 10.1080/010503900750042743. PMID 10990016
• Dai K, Ding L, Yang X, Wang S, Rong Z. Gut Microbiota and Neurodevelopment in Preterm Infants: Mechanistic Insights and Prospects for Clinical Translation. Microorganisms. 2025 Sep 22;13(9):2213. doi: 10.3390/microorganisms13092213. PMID 41011544

Identifiers

NCT: NCT07617181 · 2026R020- F01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗