An interventional study of Probiotic Mixture (Bifidobacterium animalis subsp. lactis Bb-12 and Lacticaseibacillus rhamnosus LGG) in Premature Birth, Neurodevelopmental Disorders and Dysbiosis, sponsored by Fudan University. Not yet recruiting at 1 site in China. Open to participants aged 23 Weeks to 25 Weeks. Per ClinicalTrials.gov, last updated 2026-06-01.
Sponsored by Fudan University · Not applicable, Interventional, and Prevention
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.
2,550 studies on the registry are indexed under Premature Birth; 500 are open to participants now.
This study's planned enrollment of 116 is above the median of 84 across 1,666 interventional studies indexed under Premature Birth.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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)
Preterm infants in this group will receive routine neonatal follow-up and standard infant feeding practices without additional probiotic supplementation for 6 months.
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.
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
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
Plan to share: No — IPD will not be shared to protect the privacy of the infants and their families, as the data includes sensitive medical history and early-life developmental metrics. Furthermore, the dataset contains proprietary information intended for doctoral thesis completion and subsequent intellectual property considerations within the host institution.
This study is not yet recruiting, as verified in May 2026. You cannot join it, but the record below documents what was studied.
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