Association of caffeine citrate administration with necrotising enterocolitis in infants < 32 weeks' gestation: a retrospective cohort study.

Authors

Xiaoshan Hu, Lin Yuan, Qifeng Wang, Li Zhu, Dan Dang, Yongping Fu, Hua Gong, Shuping Han, Jie Yang, Chinese Neonatal Network

Published in

BMJ open. Volume 16. Issue 8. Pages e113224. Aug 14, 2026. Epub Aug 14, 2026.

Abstract

To examine the association between caffeine citrate administration and necrotising enterocolitis (NEC) in very preterm infants (VPIs).
A multicentre retrospective cohort study.
Level III neonatal intensive care units participating in the Chinese Neonatal Network.
The participants comprised neonates with a gestational age of under 32 weeks.
Exposure to caffeine citrate administration after birth.
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.
A 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).
While 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).

PMID:
42601100
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.

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