Probiotics Supplementation for Neurodevelopment in Preterm Infants

Fudan University

Status: Not yet enrolling

Conditions: Dysbiosis; Neurodevelopmental Disorders; Premature Birth

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

Study type: Interventional

Funder types: Other

Identifiers

NCT07617181

2026R020- F01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 116 estimated patients

Sex: All

Ages: 23 to 25 weeks old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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116 participants in 2 patient groups

Probiotic Intervention Group

Experimental group

Description:

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

Treatment:

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

Standard Care Group

No Intervention group

Description:

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