Premature BirthNCT07617181
Probiotics Supplementation for Neurodevelopment in Preterm Infants
A study testing Probiotic Mixture (Bifidobacterium animalis subsp. lactis Bb-12 and Lacticaseibacillus rhamnosus LGG) in people with Premature Birth and Neurodevelopmental Disorders, run by Fudan University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 23 to 25 weeks
- Conditions the study is for
- Premature Birth, Neurodevelopmental Disorders, Dysbiosis
- What is being tested?
- Probiotic Mixture (Bifidobacterium animalis subsp. lactis Bb-12 and Lacticaseibacillus rhamnosus LGG)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 116 participants
- Where
- 1 siteChina
- Study dates
- Jun 2026to Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 23 to 25 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Gengsheng He, PhD contact
China1 site
Shanghai Children's Hospital
Shanghai, Shanghai Municipality, 200062
WenXian Wang, MD, +86 13816964779, 24111020016@m.fudan.edu.cn
Jinjin Chen, Professor
About this study
Official title: Effect of Gut Microbiota Remodeling Via Probiotics Supplementation on Neurodevelopment in Preterm Infants: A Randomized Controlled Trial
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.
Read the detailed 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.
- Conditions
- Premature Birth, Neurodevelopmental Disorders, Dysbiosis
- Being tested
- Probiotic Mixture (Bifidobacterium animalis subsp. lactis Bb-12 and Lacticaseibacillus rhamnosus LGG)
- Keywords
- Probiotics, Gut-Brain Axis, Neonatal Antibiotic Exposure, Preterm Infants
- Medical subject headings
- Premature Birth, Neurodevelopmental Disorders, Dysbiosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| Probiotic Intervention Group | Experimental | Preterm infants in this group will receive standard care plus a daily oral probiotic mixture for 6 months. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 6 months post-intervention
Secondary outcomes (4)
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).
Measured: 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 (%)
Measured: 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.
Measured: 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)
Measured: Baseline, 3 months and 6 months post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2026
- Study startJun 2026 (estimated)
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Premature BirthStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 116 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gengsheng He, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07617181
- Sponsor's protocol ID
- 2026R020- F01
- Status last verified
- May 2026
- First submitted
- 18 May 2026
- Last updated
- 1 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Publications
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.
PubMed 10056840FOXON GE. Cinematographic technique for amphibian blood circulation. Nature. 1953 May 2;171(4357):801-2. doi: 10.1038/172801b0. No abstract available.
PubMed 13054730Stenfelt 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.
PubMed 10990016Dai 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.
PubMed 41011544
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Gut Microbiota Remodeling Via Probiotics Supplementation on Neurodevelopment in Preterm Infants: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07617181
- Acronym / sponsor ID
- 2026R020- F01
- Conditions
- Premature Birth, Neurodevelopmental Disorders, Dysbiosis
- Keywords
- Probiotics, Gut-Brain Axis, Neonatal Antibiotic Exposure, Preterm Infants
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 116 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- Jun 2026 (estimated)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 1 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotic Intervention Group | Experimental | Dietary Supplement: Probiotic Mixture (Bifidobacterium animalis subsp. lactis Bb-12 and Lacticaseibacillus rhamnosus LGG)Preterm infants in this group will receive standard care plus a daily oral probiotic mixture for 6 months. |
| 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. |
Who may qualify
- Ages
- 23 to 25 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Probiotic Mixture (Bifidobacterium animalis subsp. lactis Bb-12 and Lacticaseibacillus rhamnosus LGG)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. | Dietary supplement | Probiotic Intervention Group |
Primary outcome
Mean Neurodevelopmental Assessment Score
Time frame: Baseline and 6 months post-intervention
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.
4 secondary outcomes
Change from Baseline in Gut Microbiota Alpha Diversity (Chao1 and Shannon Index Values)
Time frame: Baseline and 6 months post-intervention
Relative Abundance of Specific Gut Microbiota Taxa
Time frame: Baseline and 6 months post-intervention
Concentration of Fecal Short-Chain Fatty Acids (SCFAs)
Time frame: Baseline, 3 months and 6 months post-intervention
Concentration of Systemic Inflammatory Markers
Time frame: Baseline, 3 months and 6 months post-intervention
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2026.
- Background: PubMed 10056840Kajzar 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.
- Background: PubMed 13054730FOXON GE. Cinematographic technique for amphibian blood circulation. Nature. 1953 May 2;171(4357):801-2. doi: 10.1038/172801b0. No abstract available.
- Background: PubMed 10990016Stenfelt 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.
- Background: PubMed 41011544Dai 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.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Gengsheng He, PhD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotic Mixture (Bifidobacterium animalis subsp. lactis Bb-12 and Lacticaseibacillus rhamnosus LGG) in people with Premature Birth and Neurodevelopmental Disorders, run by Fudan University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 1 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact WenXian Wang, Doctor (+86 13816964779, 24111020016@m.fudan.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Neurodevelopmental Assessment Score (time frame: Baseline and 6 months post-intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07617181, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2026.