ArticleBMJ open2026
Association of caffeine citrate administration with necrotising enterocolitis in infants < 32 weeks' gestation: a retrospective cohort study.
Article in BMJ open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveTo examine the association between caffeine citrate administration and necrotising enterocolitis (NEC) in very preterm infants (VPIs).
designA multicentre retrospective cohort study.
settingLevel III neonatal intensive care units participating in the Chinese Neonatal Network.
participantsThe participants comprised neonates with a gestational age of under 32 weeks.
interventionsExposure to caffeine citrate administration after birth. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures were the incidence of NEC (≥stage IIA) 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.
resultsA total of 45 624 VPIs were included. Among 36 514 who received at least one dose of caffeine citrate, 2315 (6.3%) developed NEC (≥stage IIA) and 849 (2.3%) experienced surgical NEC. Among 9110 VPIs without caffeine exposure, 544 (6.0%) developed NEC (≥stage IIA) and 263 (2.9%) experienced surgical NEC. Caffeine citrate exposure did not affect the incidence of NEC (≥stage IIA) between groups (adjusted OR (aOR), 1.01; 95% CI 0.83 to 1.24; adjusted absolute risk (aAR), -0.15; 95% CI -1.21 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% CI 0.64 to 0.89; aAR, -0.92; 95% CI -1.55 to -0.29). In subgroup analysis, caffeine citrate administration was associated with a reduction in the incidence of NEC (≥stage IIA) among VPIs receiving invasive ventilation at admission (aOR, 0.8; 95% CI 0.67 to 0.94; aAR, -2.04; 95% CI -3.82 to -0.25) and vasopressors before NEC occurred (aOR, 0.64; 95% CI 0.52 to 0.78; aAR, -5.17; 95% CI -7.94 to -2.39).
conclusionsWhile the incidence of NEC (≥stage IIA) 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 (≥stage IIA).
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