Probiotics Supplementation for Neurodevelopment in Preterm Infants

N/ANot Yet RecruitingNCT07617181

Fudan University116 enrolled

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

Eligibility

Sex: ALLMin age: 23 WeeksMax age: 25 Weeks

Medical Language ↔ Plain English

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).

Outcomes

Primary Outcomes

Mean Neurodevelopmental Assessment Score

Neurodevelopmental status evaluated using the Gesell Developmental Schedules (yielding Developmental Quotients \[DQs\]) or the Ages \& Stages Questionnaires, Third Edition (ASQ-3). The reported value in the results data table will be the mean score of the participants in each group. * For the Gesell Developmental Schedules: The assessment yields a Developmental Quotient (DQ) for various developmental domains. DQ scores typically range from 0 to over 100, where a score of 100 represents the normative average. Higher DQ scores indicate a better neurodevelopmental outcome (scores below 70 indicate developmental delay). * For the ASQ-3: The questionnaire monitors five developmental domains (Communication, Gross Motor, Fine Motor, Problem Solving, and Personal-Social). Each domain is scored from 0 to 60, yielding a total combined score ranging from a minimum of 0 to a maximum of 300. Higher total scores indicate a better neurodevelopmental outcome.

Time frame: Baseline and 6 months post-intervention

Secondary Outcomes

Change from Baseline in Gut Microbiota Alpha Diversity (Chao1 and Shannon Index Values)

Evaluation of longitudinal changes in gut microbiota alpha diversity based on 16S ribosomal RNA (16S rRNA) gene sequencing. The results data table will report the mean change from baseline in Chao1 and Shannon indices (dimensionless scores).

Time frame: Baseline and 6 months post-intervention

Relative Abundance of Specific Gut Microbiota Taxa

The percentage of key bacterial groups (specifically targeting the supplemented strains Bifidobacterium and Lacticaseibacillus) relative to total sequences, determined via 16S rRNA gene sequencing. The results data table will report the mean relative abundance percentage (%)

Time frame: Baseline and 6 months post-intervention

Concentration of Fecal Short-Chain Fatty Acids (SCFAs)

Concentrations of specific fecal short-chain fatty acids (including acetate, propionate, and butyrate) quantified using gas chromatography-mass spectrometry (GC-MS) targeted metabolomics. The results data table will report the mean concentration in micromoles per gram (umol/g) of wet feces.

Time frame: Baseline, 3 months and 6 months post-intervention

Concentration of Systemic Inflammatory Markers

Circulating levels of specific systemic inflammatory mediators (specifically Interleukin-6 \[IL-6\] and Tumor Necrosis Factor-alpha \[TNF-ɑ\]) measured in blood samples using Enzyme-Linked Immunosorbent Assay (ELISA) to evaluate host-microbe signaling pathways. The results data table will report the mean concentration in picograms per milliliter (pg/mL)

Time frame: Baseline, 3 months and 6 months post-intervention

Probiotics Supplementation for Neurodevelopment in Preterm Infants

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts