Dietary Pattern Intervention for Neurodevelopment in Preterm Infants

Effect of Gut Microbiota Remodeling Via Structured Prebiotic Dietary Pattern on Neurodevelopment in Preterm Infants: A Randomized Controlled Trial

The purpose of this randomized controlled trial is to evaluate the effect of a structured, high-prebiotic dietary pattern on the neurodevelopmental outcomes of preterm infants. The intervention lasts for 6 months and aims to promote the growth of endogenous beneficial gut bacteria through targeted complementary feeding. 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 and tryptophan metabolites), and systemic inflammatory markers.

Study Overview

• Status: Not yet recruiting
• Conditions: Neurodevelopmental Disorders; Dysbiosis; Preterm
• Intervention / Treatment: Behavioral: Structured High-Prebiotic Dietary Pattern

Detailed Description

Preterm infants frequently face early-life gut dysbiosis due to perinatal complications and antibiotic exposure, which may adversely affect their neurodevelopment via the microbiota-gut-brain axis. While exogenous probiotics are one approach, modulating the gut microbiota through endogenous substrates-specifically, structured dietary interventions-offers a sustainable and highly translational alternative.

This single-blind, randomized controlled trial aims to evaluate the efficacy of a structured, high-prebiotic complementary feeding pattern on neurodevelopmental outcomes. Eligible preteum infants (aged 6 to 12 months, corrected age) will be randomized into the dietary intervention group or the standard care control group. Families in the intervention group will receive individualized, face-to-face guidance and tailored recipes from a registered dietitian, focusing on the scientific introduction of prebiotic-rich complementary foods according to the infant's age. The intervention spans 6 months.

Outcomes will be evaluated using the Gesell Developmental Schedules or ASQ-3. Concurrently, fecal and blood samples will be collected to analyze the dynamic shifts in gut microbiota composition and key metabolic pathways . This study will help elucidate whether structured dietary patterns can effectively reshape the gut microbiota and confer neuroprotective benefits in preterm infants.

• Study Type: Interventional
• Enrollment (Estimated): 116
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: WenXian Wang, Doctor; Phone Number: +86 13816964779; Email: 24111020016@m.fudan.edu.cn

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200062
      • Shanghai Children's Hospital
      • Contact: Jinjin Chen, doctor; Phone Number: +86 13816964779; Email: 24111020016@m.fudan.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Structured Dietary Pattern Group; Individualized, face-to-face guidance and tailored recipes provided by a registered dietitian, focusing on the scientific introduction of prebiotic-rich complementary foods to promote endogenous beneficial gut bacteria over a 6-month period.	Behavioral: Structured High-Prebiotic Dietary Pattern; Individualized, face-to-face guidance and tailored recipes provided by a registered dietitian, focusing on the scientific introduction of prebiotic-rich complementary foods to promote endogenous beneficial gut bacteria over a 6-month period.
No Intervention: Standard Care Group; Preterm infants in this group will receive routine neonatal follow-up and standard infant feeding practices for 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurodevelopmental Status Assessed by the Gesell Developmental Schedules (GDS)	Neurodevelopmental trajectories will be quantitatively evaluated using the Gesell Developmental Schedules (GDS), which yield Developmental Quotients (DQs) across multiple domains (motor, adaptive, language, and personal-social). The DQ is a standardized score; a higher DQ score indicates better neurodevelopmental status and progression.	Baseline and 6 months post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parent-Reported Neurodevelopment Assessed by the Ages and Stages Questionnaires, Third Edition (ASQ-3)	Neurodevelopment will be secondarily assessed using the Ages and Stages Questionnaires, Third Edition (ASQ-3), a parent-completed screening tool. It evaluates communication, gross motor, fine motor, problem-solving, and personal-social skills. Higher scores indicate better developmental milestones achievement.	Baseline and 6 months post-intervention
Change in Fecal Short-Chain Fatty Acid (SCFA) Concentrations Assessed by Gas Chromatography-Mass Spectrometry (GC-MS)	Targeted metabolomic profiling will be conducted to quantify fecal SCFA concentrations (primarily acetate, propionate, and butyrate) using Gas Chromatography-Mass Spectrometry (GC-MS). A quantitative assessment of these microbial metabolites provides insight into gut fermentation capacity. Data will be reported in micromoles per gram (μmol/g) of wet feces.	Baseline, 3 months, and 6 months post-intervention
Change in Fecal Tryptophan-Indole Derivatives Assessed by Liquid Chromatography-Mass Spectrometry (LC-MS)	Targeted metabolomic analysis using Liquid Chromatography-Mass Spectrometry (LC-MS) will be utilized to quantify the concentrations of specific fecal tryptophan-indole derivatives, which are crucial gut-brain axis signaling molecules. Data will be reported in nanograms per gram (ng/g) or micrograms per gram (μg/g) of feces.	Baseline, 3 months, and 6 months post-intervention
Change in Systemic Inflammatory Cytokine Levels Assessed by Enzyme-Linked Immunosorbent Assay (ELISA)	Systemic signaling pathways will be evaluated by quantifying the serum concentrations of key inflammatory cytokines (e.g., IL-6, TNF-alpha) using Enzyme-Linked Immunosorbent Assay (ELISA) kits. Data will be reported in picograms per milliliter (pg/mL).	Baseline, 3 months, and 6 months post-intervention
Change in Gut Microbiota Alpha Diversity (Shannon Index) Assessed by 16S rRNA Sequencing	The composition and diversity of the gut microbiota will be evaluated using 16S rRNA gene sequencing of fecal samples. Specifically, the Shannon Index will be calculated to assess alpha diversity (species richness and evenness) within individual samples. A higher Shannon Index value indicates a more diverse microbial community.	Baseline and 6 months post-intervention

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 1, 2026
• First Submitted That Met QC Criteria: July 9, 2026
• First Posted (Actual): July 14, 2026

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Prebiotics; Preterm Infants; Gut-Brain Axis; Dietary Pattern; Neonatal Antibiotic Exposure
• Additional Relevant MeSH Terms: Urogenital Diseases; Mental Disorders; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Pathological Conditions, Signs and Symptoms; Premature Birth; Neurodevelopmental Disorders; Dysbiosis
• Other Study ID Numbers: 2026R020- F02

Drug and device information, study documents

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