Dysbiosis, Neurodevelopmental Disorders, Preterm
Conditions
Keywords
Dietary Pattern, Prebiotics, Gut-Brain Axis, Neonatal Antibiotic Exposure, Preterm Infants
Brief summary
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.
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.
Interventions
BEHAVIORALStructured 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.
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
6 Months to 6 Months
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neurodevelopmental Status Assessed by the Gesell Developmental Schedules (GDS) | Baseline and 6 months post-intervention | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Parent-Reported Neurodevelopment Assessed by the Ages and Stages Questionnaires, Third Edition (ASQ-3) | Baseline and 6 months post-intervention | 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. |
| Change in Fecal Short-Chain Fatty Acid (SCFA) Concentrations Assessed by Gas Chromatography-Mass Spectrometry (GC-MS) | Baseline, 3 months, and 6 months post-intervention | 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. |
| Change in Fecal Tryptophan-Indole Derivatives Assessed by Liquid Chromatography-Mass Spectrometry (LC-MS) | Baseline, 3 months, and 6 months post-intervention | 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. |
| Change in Systemic Inflammatory Cytokine Levels Assessed by Enzyme-Linked Immunosorbent Assay (ELISA) | Baseline, 3 months, and 6 months post-intervention | 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). |
| Change in Gut Microbiota Alpha Diversity (Shannon Index) Assessed by 16S rRNA Sequencing | Baseline and 6 months post-intervention | 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. |
Countries
China
Contacts
CONTACTWenXian Wang, Doctor
Outcome results
None listed