{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:15:41Z","timestamp":1788509741018,"version":"build-2803163510"},"reference-count":44,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"unspecified","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,7,3]]},"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To examine the association between caffeine citrate administration and necrotising enterocolitis (NEC) in very preterm infants (VPIs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A multicentre retrospective cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Level III neonatal intensive care units participating in the Chinese Neonatal Network.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>The participants comprised neonates with a gestational age of under 32 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>Exposure to caffeine citrate administration after birth.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Primary and secondary outcome measures<\/jats:title>\n                    <jats:p>Primary outcome measures were the incidence of NEC (\u2265stage\u2009IIA) and surgical NEC. Secondary outcome measures included severe neonatal morbidities, including severe intraventricular haemorrhages, severe retinopathy of prematurity, late-onset sepsis, bronchopulmonary dysplasia, death, duration of parenteral nutrition and length of neonatal intensive care unit stay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 45 624 VPIs were included. Among 36\u2009514 who received at least one dose of caffeine citrate, 2315 (6.3%) developed NEC (\u2265stage\u2009IIA) and 849 (2.3%) experienced surgical NEC. Among 9110 VPIs without caffeine exposure, 544 (6.0%) developed NEC (\u2265stage\u2009IIA) and 263 (2.9%) experienced surgical NEC. Caffeine citrate exposure did not affect the incidence of NEC (\u2265stage\u2009IIA) between groups (adjusted OR (aOR), 1.01; 95%\u2009CI 0.83 to 1.24; adjusted absolute risk (aAR), \u22120.15; 95%\u2009CI \u22121.21 to 0.92); however, its early administration (within 72 hours after birth) was associated with a lower incidence of surgical NEC (aOR, 0.76; 95%\u2009CI 0.64 to 0.89; aAR, \u22120.92; 95%\u2009CI \u22121.55 to \u22120.29). In subgroup analysis, caffeine citrate administration was associated with a reduction in the incidence of NEC (\u2265stage\u2009IIA) among VPIs receiving invasive ventilation at admission (aOR, 0.8; 95%\u2009CI 0.67 to 0.94; aAR, \u22122.04; 95%\u2009CI \u22123.82 to \u22120.25) and vasopressors before NEC occurred (aOR, 0.64; 95%\u2009CI 0.52 to 0.78; aAR, \u22125.17; 95%\u2009CI \u22127.94 to \u22122.39).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>While the incidence of NEC (\u2265stage\u2009IIA) in VPIs has not been affected by caffeine citrate, early administration (within 72 hours after birth) was associated with a reduced incidence of surgical NEC. Furthermore, among VPIs who received invasive ventilation at admission and vasopressors, the administration of caffeine citrate was potentially correlated with a decreased occurrence of NEC (\u2265stage\u2009IIA).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-113224","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T12:40:34Z","timestamp":1786711234000},"page":"e113224","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Association of caffeine citrate administration with necrotising enterocolitis in infants &lt; 32 weeks\u2019 gestation: a retrospective cohort study"],"prefix":"10.1136","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5131-0816","authenticated-orcid":false,"given":"Xiaoshan","family":"Hu","sequence":"first","affiliation":[{"name":"Women\u2019s Hospital of Nanjing Medical University, Nanjing Women and Children\u2019s Healthcare Hospital, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Children\u2019s Hospital of Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Women\u2019s Hospital of Nanjing Medical University, Nanjing Women and Children\u2019s Healthcare Hospital, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhu","sequence":"additional","affiliation":[{"name":"NICU, Children\u2019s Hospital of Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Dang","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Jilin University First Hospital, Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongping","family":"Fu","sequence":"additional","affiliation":[{"name":"Shenzhen Maternity and Child Healthcare Hospital, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Gong","sequence":"additional","affiliation":[{"name":"Chongqing Health Center for Women and Children, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuping","family":"Han","sequence":"additional","affiliation":[{"name":"Nanjing Medical University Affiliated Healthcare Hospital for Women and Infants, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6892-8851","authenticated-orcid":false,"given":"Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Neonatal Diseases, Children\u2019s Hospital of Fudan University, Shanghai, China"},{"name":"Children's Hospital of Fudan University National Children\u2019s Medical Center, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"2026090400401893000_16.8.e113224.1","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2018.1490719"},{"key":"2026090400401893000_16.8.e113224.2","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2023-061273","article-title":"A Quality Improvement Initiative to Reduce Necrotizing Enterocolitis in Very Preterm Infants","volume":"152","author":"Alshaikh","year":"2023","journal-title":"Pediatrics"},{"key":"2026090400401893000_16.8.e113224.3","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1159\/000504371","article-title":"An Overview of Systematic Reviews of Randomized-Controlled Trials for Preventing Necrotizing Enterocolitis in Preterm Infants","volume":"117","author":"Xiong","year":"2020","journal-title":"Neonatology"},{"key":"2026090400401893000_16.8.e113224.4","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24032471","article-title":"Necrotizing Enterocolitis: The Role of Hypoxia, Gut Microbiome, and Microbial Metabolites","volume":"24","author":"Kaplina","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2026090400401893000_16.8.e113224.5","doi-asserted-by":"publisher","DOI":"10.1177\/1535370219891971"},{"key":"2026090400401893000_16.8.e113224.6","doi-asserted-by":"crossref","unstructured":"Lauren T , Joseph WW , David G . 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