Probiotics Supplementation for Neurodevelopment in Preterm Infants

NCT07617181 | Not Yet Recruiting

• 1 other identifier: 2026R020- F01
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Premature Birth; Neurodevelopmental Disorders; Dysbiosis

Keywords

Probiotics; Gut-Brain Axis; Neonatal Antibiotic Exposure; Preterm Infants

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline and 6 months post-intervention

Secondary Outcomes (4)

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

  Baseline and 6 months post-intervention

• Relative Abundance of Specific Gut Microbiota Taxa

  Baseline and 6 months post-intervention

• Concentration of Fecal Short-Chain Fatty Acids (SCFAs)

  Baseline, 3 months and 6 months post-intervention

• Concentration of Systemic Inflammatory Markers

  Baseline, 3 months and 6 months post-intervention

Study Arms (2)

Probiotic Intervention Group

EXPERIMENTAL

Preterm infants in this group will receive standard care plus a daily oral probiotic mixture for 6 months.

Dietary Supplement: Probiotic Mixture (Bifidobacterium animalis subsp. lactis Bb-12 and Lacticaseibacillus rhamnosus LGG)

Standard Care Group

NO INTERVENTION

Preterm infants in this group will receive routine neonatal follow-up and standard infant feeding practices without additional probiotic supplementation for 6 months.

Interventions

Probiotic Mixture (Bifidobacterium animalis subsp. lactis Bb-12 and Lacticaseibacillus rhamnosus LGG) DIETARY_SUPPLEMENT

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.

Probiotic Intervention Group

Eligibility Criteria

• Age: 23 Weeks - 25 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Shanghai Children's Hospital

Shanghai, Shanghai Municipality, 200062, China

Location

Related Publications (4)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Premature Birth; Neurodevelopmental Disorders; Dysbiosis

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

WenXian Wang, Doctor

CONTACT

+86 13816964779; 24111020016@m.fudan.edu.cn

Gengsheng He, PhD

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 18, 2026
• First Posted: June 1, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 1, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)