Caffeine exposure and acute kidney injury in premature infants with necrotizing enterocolitis and spontaneous intestinal perforation

Pediatr Nephrol. 2019 Apr;34(4):729-736. doi: 10.1007/s00467-018-4140-y. Epub 2018 Nov 10.


Background: Acute kidney injury (AKI) is common in preterm infants, but specific therapies remain scarce. Recent studies have demonstrated an association between caffeine exposure and less frequent AKI in the first 7-10 days after birth. We hypothesized that patients with necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) would provide a better natural model of AKI to evaluate this association.

Methods: We reviewed all premature patients diagnosed with NEC or SIP at our institution from 2008 to 2014. AKI was defined by change in serum creatinine using the neonatal Kidney Disease: Improving Global Outcomes definition. Caffeine was prescribed for apnea of prematurity and caffeine exposure was determined by chart review.

Results: A total of 146 patients with NEC/SIP were reviewed. Of these, 119 (81.5%) received caffeine, and 91 (62.3%) developed AKI. AKI occurred less frequently in patients who received caffeine than in those who did not (55.5% vs. 92.6%; odds ratio (OR) 0.10; 95% confidence interval (CI) 0.02-0.44). This association persisted in multivariable models after adjustment for potential confounders (adjusted OR 0.08; 95% CI 0.01-0.42; number needed to be exposed to caffeine to prevent one case of AKI = 2.6). Although baseline serum creatinine did not differ by caffeine exposure, patients receiving caffeine had lower peak creatinine (median 1.0 mg/dl vs. 1.5 mg/dl; p = 0.008) and absolute creatinine change (median 0.42 mg/dl vs. 0.68 mg/dl; p = 0.003) than those who did not.

Conclusions: Caffeine exposure in preterm infants with NEC/SIP is associated with decreased incidence and severity of AKI.

Keywords: Acute kidney injury; Caffeine; Infant; Intestinal perforation; Low birth weight; Necrotizing enterocolitis; Premature.

MeSH terms

  • Acute Kidney Injury / diagnosis
  • Acute Kidney Injury / epidemiology
  • Acute Kidney Injury / prevention & control*
  • Age Factors
  • Caffeine / therapeutic use*
  • Enterocolitis, Necrotizing / diagnosis
  • Enterocolitis, Necrotizing / drug therapy*
  • Enterocolitis, Necrotizing / epidemiology
  • Female
  • Gestational Age
  • Humans
  • Incidence
  • Infant, Newborn
  • Infant, Premature
  • Intestinal Perforation / diagnosis
  • Intestinal Perforation / drug therapy*
  • Intestinal Perforation / epidemiology
  • Male
  • Premature Birth* / epidemiology
  • Protective Factors
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome
  • Virginia / epidemiology


  • Caffeine