{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:14:52Z","timestamp":1774430092098,"version":"3.50.1"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>This study demonstrates that neonatal sepsis, blood transfusion, combined antibiotic use, asphyxia, and maternal gestational diabetes (GDM) are independent risk factors for NEC. By utilizing a 1:1 matched case-control design, we effectively eliminated the confounding effects of gestational age and birth weight, revealing critical perinatal drivers of the disease. The resulting prediction model (AUC\u2009=\u20090.937) provides a robust tool for early screening. These findings underscore the urgent need for enhanced antibiotic stewardship and rigorous maternal GDM management to reduce NEC incidence and improve outcomes in high-risk preterm infants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Identifying independent clinical risk factors for necrotizing enterocolitis (NEC) facilitates early screening of high-risk preterm infants and enables the development of targeted prevention strategies.This retrospective study explored the influencing factors of NEC and applied logistic regression analysis to identify the key contributors to NEC onset, aiming to provide evidence for clinical diagnosis and treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A 1:1 matched case-control study was conducted, involving 172 preterm infants with NEC and 172 controls matched by GA (\u00b11 week), BW (\u00b1100\u2005g), and admission time. Univariate and multivariable logistic regression analyses were performed to identify independent risk factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 172 preterm infants with NEC (study group) and 172 matched non-NEC preterm infants (control group) were enrolled in this retrospective case-control study. Univariate analysis revealed significant differences between the two groups in preterm premature rupture of membranes (PPROM), gestational diabetes mellitus (GDM), combined antibiotic use, blood product transfusion, neonatal sepsis, and neonatal asphyxia (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.05). Multivariate logistic regression analysis identified independent risk factors for NEC in preterm infants, including neonatal sepsis (OR\u2009=\u20092.522, 95%CI: 1.403\u20134.538,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.002), blood transfusion (OR\u2009=\u20092.18, 95%CI: 1.245\u20133.809,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.008), neonatal asphyxia (OR\u2009=\u20091.887, 95%CI: 1.085\u20133.274,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.024), GDM (OR\u2009=\u20091.824, 95%CI: 1.102\u20133.020,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.018), and combined antibiotic use (OR\u2009=\u20091.976, 95%CI: 1.305\u20132.972,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.001). The Hosmer-Lemeshow test confirmed good fit of the regression model (\n                      <jats:italic>\u03c7<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200913.152,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.071). Receiver operating characteristic (ROC) curve analysis showed that the risk prediction model constructed with these independent factors had an area under the curve (AUC) of 0.937 (95%CI: 0.915\u20130.960), with a sensitivity of 93.8% and specificity of 79.5%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Sepsis, blood transfusion, combined antibiotics, asphyxia, and maternal GDM are key independent predictors of NEC. Clinicians should implement targeted monitoring and stewardship, particularly regarding antibiotic use and GDM management, to mitigate NEC risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1807022","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:47:41Z","timestamp":1774421261000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Risk factors for necrotizing enterocolitis in preterm infants: a 1:1 matched case-control study"],"prefix":"10.3389","volume":"14","author":[{"given":"Lie","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The First People\u2019s Hospital of Neijiang","place":["Neijiang, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Children\u2019s Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomei","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First People\u2019s Hospital of Neijiang","place":["Neijiang, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meile","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The First People\u2019s Hospital of Yinchuan","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Science and Education, The First People\u2019s Hospital of Neijiang","place":["Neijiang, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1111\/j.1365-3016.2006.00756.x","article-title":"Necrotising enterocolitis hospitalisations among neonates in the United States","volume":"20","author":"Holman","year":"2006","journal-title":"Paediatr Perinat Epidemiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1542\/peds.2009-2959","article-title":"Neonatal outcomes of extremely preterm infants from the NICHD neonatal research network","volume":"126","author":"Stoll","year":"2006","journal-title":"Pediatrics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"F182","DOI":"10.1136\/archdischild-2017-313880","article-title":"Incidence of neonatal necrotising enterocolitis in high-incomecountries: a systematic review","volume":"103","author":"Battersby","year":"2018","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"B4","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1542\/pir.2017-0002","article-title":"Necrotizing enterocolitis","volume":"38","author":"Rich","year":"2017","journal-title":"Pediatr Rev."},{"key":"B5","doi-asserted-by":"publisher","first-page":"33","DOI":"10.3389\/fped.2020.00033","article-title":"Mortality and morbidity in infants < 34 weeks\u2019 gestation in 25 NICUs in China: a prospective cohort study","volume":"8","author":"Jiang","year":"2020","journal-title":"Front Pediatr"},{"key":"B6","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.jpeds.2019.11.011","article-title":"Contemporary outcomes for infants with necrotizing enterocolitis-a systematic review","volume":"220","author":"Jones","year":"2020","journal-title":"J Pediatr"},{"key":"B7","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1016\/j.jpedsurg.2018.02.014","article-title":"Necrotizing enterocolitis in patients with congenital heart disease: a single center experience","volume":"53","author":"Lau","year":"2018","journal-title":"J Pediatr Surg"},{"key":"B8","first-page":"24","article-title":"Analysis of pathogenic bacteria and surgical treatment of neonatal necrotizing enterocolitis","volume":"22","author":"Xuguang","year":"2020","journal-title":"Chin J Nosocomiol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.pedn.2008.02.031","article-title":"The effects of perinatal morbidity and environmental factors on health status of preterm children at age 12","volume":"24","author":"Miller","year":"2009","journal-title":"J Pediatr Nurs"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e20","DOI":"10.1542\/peds.2015-0389","article-title":"A multifaceted approach to improving outcomes in the NICU: the pediatrix 100 000 babies campaign","volume":"137","author":"Ellsbury","year":"2016","journal-title":"Pediatrics"},{"key":"B11","doi-asserted-by":"publisher","first-page":"874976","DOI":"10.3389\/fped.2022.874976","article-title":"Evaluation of risk and preventive factors for necrotizing enterocolitis in premature newborns. A systematic review of the literature","volume":"10","author":"Campos-Martinez","year":"2022","journal-title":"Front Pediatr"},{"key":"B12","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/S0031-3955(16)34975-6","article-title":"Necrotizing enterocolitis: treatment based on staging criteria","volume":"33","author":"Walsh","year":"1986","journal-title":"Pediatr Clin North Am"},{"key":"B13","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1097\/MPG.0b013e318174e855","article-title":"Necrotising enterocolitis in very low birth weight infants in Italy: incidence and non-nutritional risk factors","volume":"47","author":"Gagliardi","year":"2008","journal-title":"J Pediatr Gastroenterol Nutrition"},{"key":"B14","doi-asserted-by":"publisher","first-page":"F289","DOI":"10.1136\/adc.2002.021923","article-title":"Early enteral feeding and nosocomial sepsis in very low birthweight infants","volume":"89","author":"Flidel-Rimon","year":"2004","journal-title":"Arch Dis Childhood Fetal Neonatal Ed"},{"key":"B15","first-page":"464","article-title":"A case-control study of microecological agents for the prevention and treatment of necrotizing small bowel colitis in neonates","volume":"6","author":"Li","year":"2006","journal-title":"Chin J Contemp Pediatr"},{"key":"B16","first-page":"14","article-title":"Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants","volume":"6","author":"Pammi","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"B17","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1038\/s41575-022-00594-x","article-title":"Bench to bedside\u2014new insights into the pathogenesis of necrotizing enterocolitis","volume":"19","author":"Hackam","year":"2022","journal-title":"Nat Rev Gastro- Enterol Hepatol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"9584","DOI":"10.1074\/jbc.M113.526517","article-title":"Toll-like receptor 4-mediated endoplasmic reticulum stress in intestinal crypts inducesnecrotizing enterocolitis","volume":"289","author":"Afrazi","year":"2014","journal-title":"J Biol Chem"},{"key":"B19","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.jcmgh.2019.11.002","article-title":"A novel role for necroptosis in the pathogenesis of necrotizing enterocolitis","volume":"9","author":"Werts","year":"2020","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.jcmgh.2018.04.001","article-title":"Toll-like receptor-mediated intestinal inflammatory imbalance in the pathogenesis of necrotizing enterocolitis","volume":"6","author":"Hackam","year":"2018","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"11330","DOI":"10.1073\/pnas.1200856109","article-title":"Amniotic fluid inhibits toll-like receptor 4 signaling in the fetal and neonatal intestinal epithelium","volume":"109","author":"Good","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"B22","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1159\/000489677","article-title":"Risk factors for necrotizing enterocolitis: a prospective multicenter case-control study","volume":"114","author":"Berkhout","year":"2018","journal-title":"Neonatology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1053\/j.semperi.2016.09.021","article-title":"Should we believe in transfusion-associated enterocolitis? Applying a GRADE to the literature","volume":"41","author":"PHay","year":"2017","journal-title":"Semin Perinatol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1038\/jp.2013.60","article-title":"Packed red blood cell transfusion is an independent risk factor for necrotizing enterocolitis in premature infants","volume":"33","author":"Wan-Huen","year":"2013","journal-title":"J Perinatol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1515\/jpm-2017-0048","article-title":"Transfusion-associated necrotizing enterocolitis re-evaluated: a systematic review and meta-analysis","volume":"46","author":"Rai","year":"2018","journal-title":"J Perinatal Med"},{"key":"B26","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1001\/jama.2016.1204","article-title":"Association of red blood cell transfusion, anemia, and necrotizing enterocolitis in very low-birth-weight infants","volume":"315","author":"Patel","year":"2016","journal-title":"Jama"},{"key":"B27","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1159\/000081898","article-title":"The \u2018myth\u2019 of asphyxia and hypoxia-ischemia as primary causes of necrotizing enterocolitis","volume":"87","author":"Neu","year":"2005","journal-title":"Biol Neonate"},{"key":"B28","first-page":"908","article-title":"Meta-analysis of risk factors for necrotizing small bowel colitis in preterm infants","volume":"24","author":"Lu","year":"2022","journal-title":"Chin J Contemp Pediatr"},{"key":"B29","first-page":"5673","article-title":"Analysis of clinical characteristics and influencing factors of necrotizing small bowel colitis in preterm infants","volume":"34","author":"Li","year":"2019","journal-title":"China Matern Child Health Care"},{"key":"B30","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.jpeds.2020.06.032","article-title":"Early use of antibiotics is associated with a lower incidence of necrotizing enterocolitis in preterm, very low birth weight infants: the NEOMUNE-NeoNutriNet cohort study","volume":"227","author":"Li","year":"2020","journal-title":"J Pediatr"},{"key":"B31","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1542\/peds.2007-3423","article-title":"Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants","volume":"123","author":"Cotten","year":"2009","journal-title":"Pediatrics"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1943","DOI":"10.1038\/s41598-021-80982-6","article-title":"Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment in a randomized trial of preterm infants","volume":"11","author":"Russell","year":"2021","journal-title":"Sci Rep"},{"key":"B33","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1007\/s12098-021-04023-w","article-title":"Association between antibiotic overexposure and adverse outcomes in very-low-birth-weight infants without culture-proven sepsis or necrotizing enterocolitis: a multicenter prospective study","volume":"89","author":"Hou","year":"2022","journal-title":"Indian J Pediatr"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1807022\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:47:42Z","timestamp":1774421262000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1807022\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":33,"alternative-id":["10.3389\/fped.2026.1807022"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1807022","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]},"article-number":"1807022"}}