An observational study in NEC - Necrotizing Enterocolitis, sponsored by Guangzhou Women and Children's Medical Center. Recruiting at 2 sites in China. Open to participants aged Up to 12 Months. Per ClinicalTrials.gov, last updated 2026-11-06.
Sponsored by Guangzhou Women and Children's Medical Center · Observational
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 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.
228 studies on the registry are indexed under Enterocolitis, Necrotizing; 44 are open to participants now.
This study's planned enrollment of 1,050 is above the median of 144 across 95 observational studies indexed under Enterocolitis, Necrotizing.
Browse Enterocolitis, Necrotizing studies →Guangzhou Women and Children's Medical Center is the lead sponsor of 58 studies on the registry; 30 are open to participants now.
Counted across the registry records on this site, refreshed daily.
The criteria were revised on the registry on Nov 6, 2026. See what changed
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
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
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
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
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.
Number of infants with Bell stage II or higher necrotizing enterocolitis
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.
Time frame: From admission until discharge, transfer, or death during the index neonatal hospitalization, whichever occurs first; assessed up to 20 weeks.
Number of infants undergoing surgery for necrotizing enterocolitis
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: From admission until discharge, transfer, or death during the index neonatal hospitalization, whichever occurs first; assessed up to 20 weeks.
Started Apr 2026 (actual). Primary completion is estimated for Dec 2029, 44 months after the start.
Of 39 observational studies under Enterocolitis, Necrotizing, half reached primary completion within 29 months of starting (the median), counting those still running; a quarter within 19 and three quarters within 115. This study's planned 44 months is above that.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Guangzhou Women and Children's Medical Center