Multidimensional Dynamic Early Warning System for Neonatal Necrotizing Enterocolitis: A Multicenter Clinical Study

November 5, 2026 updated by: Guangzhou Women and Children's Medical Center

Construction of a Multidimensional Dynamic Early Warning System for Genetic-Immune-Inflammatory Disorders in Precision Prevention and Control of Neonatal Necrotizing Enterocolitis: A Multicenter Clinical Study

Necrotizing enterocolitis (NEC) is one of the most severe gastrointestinal emergencies in preterm infants, characterized by insidious onset, rapid progression, and high mortality. It can lead to serious adverse outcomes such as intestinal perforation, short bowel syndrome, and neurodevelopmental disorders, making it a critical condition that significantly impacts the survival quality and long-term prognosis of preterm infants.With the advancement of perinatal medicine in China, the survival rates of extremely low and very low birth weight infants have been continuously improving. NEC has become a critical bottleneck constraining the quality of care and long-term prognosis for preterm infants.

Previous studies have demonstrated that various perinatal and early postnatal factors, including gestational age, birth weight, infection, feeding methods, blood transfusion, mechanical ventilation, and antibiotic exposure, are associated with the occurrence of NEC. However, these clinical factors still fail to adequately explain the interindividual variations in NEC incidence risk and disease severity under similar clinical exposure conditions.Existing NEC prediction models primarily rely on static baseline variables for one-time risk assessment, lacking dynamic risk updates during hospitalization, and most are derived from single-center retrospective studies.

With the application of clinical exome sequencing (CES), the role of genetic factors in susceptibility to NEC has gradually attracted attention.The research team has previously conducted NEC risk gene screening based on CES, genetic burden analysis, and exploration of genetic-clinical factor interactions, suggesting that genetic information can provide important supplementation for NEC risk assessment.Meanwhile, dynamic changes in immune-inflammatory markers such as peripheral blood eosinophils, NLR, absolute neutrophil count, and platelet count may already exhibit abnormalities prior to the onset of NEC, providing repeatable, low-cost, and clinically available signals for early identification.Based on this, this study aims to establish a multidimensional dynamic early warning system for NEC integrating single-center preliminary genetic research foundations with multi-center retrospective/prospective validation resources. This initiative seeks to enhance the identification capability of high-risk individuals and provide evidence for subsequent precision prevention and control as well as stratified management.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Study design and objectives

This is a three-center observational cohort study combining retrospective model development and validation with subsequent prospective validation. The coordinating center is Guangzhou Women's and Children's Medical Center. The participating centers are Northwest Women's and Children's Hospital and the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. The study will evaluate whether genetic susceptibility and longitudinal immune and inflammatory markers improve prediction of necrotizing enterocolitis beyond clinical information alone.

Cohorts and separation of development from validation The development cohort will comprise eligible infants from an existing clinical exome sequencing cohort at the coordinating center. Internal validation will use resampling within this development cohort. A separate historical cohort from the coordinating center will be used for temporal validation, provided that its observation period is distinct from that of the development cohort. Independent historical cohorts from the two collaborating hospitals will provide geographic external validation. A subsequent independent cohort at the three hospitals will provide prospective validation after the prediction model and its implementation rules have been finalized.

The cohorts will not overlap. All records from the same infant will be assigned to a single cohort, and duplicate records across hospitals will be checked. Historical records will be screened using the same eligibility definitions at each site. Prospective recruitment will be consecutive among eligible infants during the defined recruitment period; no random sampling from the general population is planned.

Predictors and biological information Candidate predictors will include perinatal and early postnatal clinical characteristics, eosinophil counts and percentages, the neutrophil-to-lymphocyte ratio, absolute neutrophil counts, platelet counts, white blood cell differential measurements, and prespecified longitudinal features derived from repeated measurements. Genetic predictors will be derived from existing clinical exome sequencing or targeted gene panel results, including candidate gene burden measures and an individual weighted genetic burden score. Existing results will be used whenever available. If additional testing is required and authorized, targeted testing may use residual ethylenediaminetetraacetic acid blood from routine clinical sampling, without additional research-only phlebotomy.

Prediction timing and availability of information Predictor values, genetic information and laboratory results must be available before the outcome.The same prespecified timing rules will be applied to infants who do and do not develop the outcome.

Development and internal validation Clinical-only, genetic, dynamic inflammatory and integrated prediction models will be developed at the coordinating center. Logistic regression, including least absolute shrinkage and selection operator methods, will be considered for model development and simplification. Landmark-based or other longitudinal methods may be used in accordance with a prespecified statistical analysis plan. Internal validation will assess optimism and overfitting by resampling at the infant level. Predictor selection, transformations, missing-data procedures and model tuning will be repeated within the resampling process rather than performed once using the full dataset before internal validation.

Data management and ethics All centers will use harmonized data definitions and collection procedures, with range checks, consistency checks and review of key outcomes. Clinical and genetic information will be coded and held in separate access-controlled systems. Retrospective data will be used under the consent requirements or waivers authorized by the relevant ethics committees. Written permission from a parent or legally authorized guardian will be obtained for prospective participation and any additional genetic analysis as required by the approved protocol. Public reports will present aggregate information and will not identify individual infants.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1050

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Guangxi
      • Guangxi, Guangxi, China
        • Recruiting
        • Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region.
        • Contact:
          • Yan Mo, Ph.D.
    • Shanxi
      • Xi’an, Shanxi, China
        • Recruiting
        • Northwest Women's and Children's Hospital
        • Contact:
          • Ruimiao Bai, Ph.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 1 year (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Infants born before 32 completed weeks of gestation who receive neonatal inpatient care at Guangzhou Women's and Children's Medical Center, Northwest Women's and Children's Hospital, or the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. Historical records will support model development and retrospective independent validation. A separate cohort of eligible infants will be recruited consecutively for prospective validation after the model has been finalized.

Description

Inclusion Criteria:

  • Birth before 32 completed weeks of gestation.
  • Admission to the neonatal department of one of the three participating hospitals.
  • Availability of perinatal and hospitalization information required by the approved cohort-specific data collection plan.
  • For the development cohort, clinical exome sequencing performed during the neonatal hospitalization.
  • For retrospective validation cohorts, available clinical records and extractable longitudinal complete blood count data.
  • For the prospective cohort, written permission from a parent or legally authorized guardian for participation and for the use of residual blood for genetic analysis as required by the approved protocol.

Exclusion Criteria:

  • Congenital malformations, a defined clinical syndrome, or a chromosomal abnormality meeting the exclusion definition in the approved protocol.
  • Death or discharge against medical advice within the first 7 days after birth.
  • A confirmed pathogenic genetic diagnosis that explains the main clinical phenotype.
  • An additional infant from the same monozygotic multiple birth when one infant from that pregnancy has already been selected for analysis according to the prespecified selection rule.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: COHORT
  • Time Perspectives: OTHER

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Coordinating-center model development cohort

Eligible infants born before 32 completed weeks of gestation from an existing clinical exome sequencing cohort at the coordinating center. Their historical clinical, laboratory and genetic information will be used for model development and internal validation by resampling. These infants will not be included in any independent validation cohort.
Other: No Intervention: Observational Cohort

No intervention required.
Coordinating-center retrospective temporal validation cohort

Eligible infants from a separately defined historical period at the coordinating center who were not included in model development. The locked model will be evaluated without refitting. This cohort will be described as temporal validation only if the development and validation periods are distinct. Models requiring genetic inputs will be evaluated only in infants with compatible genetic information.
Other: No Intervention: Observational Cohort

No intervention required.
Collaborating-center retrospective external validation cohorts

Eligible infants identified from historical records at the two collaborating hospitals. These independent cohorts will be used for geographic external validation of the locked model. Performance will be reported by hospital and, where appropriate, across the collaborating hospitals. Required predictor availability, including genetic information, will be documented for each model.
Other: No Intervention: Observational Cohort

No intervention required.
Three-center prospective validation cohort

Eligible infants consecutively recruited at the three hospitals during the prospective validation period, with written permission from a parent or legally authorized guardian. They will be independent of all historical cohorts. Predictions will be generated using the finalized model and only information available at each prespecified prediction time. Predictions will not direct treatment, and clinical outcomes will be recorded prospectively.
Other: No Intervention: Observational Cohort

No intervention required.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of infants with Bell stage II or higher necrotizing enterocolitis
Time Frame: From admission until discharge, transfer, or death during the index neonatal hospitalization, whichever occurs first; assessed up to 20 weeks.

The number and proportion of infants with a first documented episode of necrotizing enterocolitis meeting Bell stage II or higher criteria during the index neonatal hospitalization. Diagnoses and disease stage will be determined from clinical and imaging information using harmonized criteria across the three centers. Bell stage I alone will not be counted as the primary event. For prediction analyses, only events occurring after the prespecified prediction time and within the prespecified prediction horizon will be used to evaluate that prediction.
From admission until discharge, transfer, or death during the index neonatal hospitalization, whichever occurs first; assessed up to 20 weeks.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of infants undergoing surgery for necrotizing enterocolitis
Time Frame: From admission until discharge, transfer, or death during the index neonatal hospitalization, whichever occurs first; assessed up to 20 weeks.

The number and proportion of infants undergoing a surgical procedure for necrotizing enterocolitis during the index neonatal hospitalization. The indication and procedure will be recorded and adjudicated using the same definition at all centers. Isolated spontaneous intestinal perforation will be distinguished from necrotizing enterocolitis. The inclusion or exclusion of peritoneal drainage in the surgical definition will be specified before analysis.
From admission until discharge, transfer, or death during the index neonatal hospitalization, whichever occurs first; assessed up to 20 weeks.
Number of infants with necrotizing enterocolitis-related death
Time Frame: From admission until discharge, transfer, or death during the index neonatal hospitalization, whichever occurs first; assessed up to 20 weeks.

The number and proportion of infants whose death during the index neonatal hospitalization is adjudicated as related to necrotizing enterocolitis using prespecified criteria applied consistently across centers. The denominator for the primary summary will be all eligible infants in the relevant cohort. Death among infants with necrotizing enterocolitis may additionally be reported as a separately labeled case-fatality proportion. All-cause death will not automatically be classified as necrotizing enterocolitis-related death.
From admission until discharge, transfer, or death during the index neonatal hospitalization, whichever occurs first; assessed up to 20 weeks.
Maximum Bell stage among infants with necrotizing enterocolitis
Time Frame: From admission until discharge, transfer, or death during the index neonatal hospitalization, whichever occurs first; assessed up to 20 weeks.

The highest Bell stage recorded during the index neonatal hospitalization among infants meeting the primary necrotizing enterocolitis outcome definition. The number of infants in each stage II and stage III subcategory will be reported according to the harmonized staging definitions. Higher stage indicates more severe disease. This categorical measure will not be treated as a newly constructed numerical severity score.
From admission until discharge, transfer, or death during the index neonatal hospitalization, whichever occurs first; assessed up to 20 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Guangzhou Women and Children's Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Liyuan Hu, Ph.D., Guangzhou Women and Children's Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 20, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 15, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 15, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 22, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 6, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2026-222A01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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