title: Evaluation of caffeine and the development of necrotizing enterocolitis.
abstract: OBJECTIVE
  To test the association between medical or surgical necrotizing enterocolitis (NEC) and caffeine administration in premature infants.
  
  
  METHODS
  This single-center, retrospective study evaluated patients admitted to a level 3 neonatal intensive care unit (NICU) over an 18-month period. All patients were evaluated for factors associated with the development of NEC including exposure to caffeine (dosing and duration), gestational age, birth weight, vasoactive medications and maternal illicit drug use.
  
  
  RESULTS
  There were 615 subjects included in the study; among these subjects, 7.3% (n = 45) developed NEC (35 subjects receiving caffeine and 10 subjects not receiving caffeine). The administration of caffeine (p = 0.008), birth weight (p = 0.014) and the use of vasopressors (p = 0.033) were associated with the development of NEC. When considering only infants with a birth weight less than 1500 g and less than 32 weeks gestation, the effects of caffeine and vasopressor use remained statistically significant (p = 0.047 and p = 0.045, respectively). The time to development of NEC did not differ statistically between patients receiving caffeine and those not receiving caffeine (p = 0.129).
  
  
  CONCLUSIONS
  A potential association between the administration of caffeine and the development of medical or surgical necrotizing enterocolitis in premature infants exists. Further investigation of dose-dependent effects and loading doses is warranted.
authors.affiliation: Department of Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA.
authors.forename: C
authors.initials: C
authors.lastname: Cox
authors.affiliation: Lancaster General Health, Lancaster, PA, USA.
authors.forename: N G
authors.initials: NG
authors.lastname: Hashem
authors.affiliation: Department of Statistics, University of South Carolina, Columbia, SC, USA.
authors.forename: J
authors.initials: J
authors.lastname: Tebbs
authors.affiliation: Department of Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA.
authors.forename: P Brandon
authors.initials: PB
authors.lastname: Bookstaver
authors.affiliation: Department of Neonatology, Palmetto Health Richland, Columbia, SC, USA.
authors.forename: V
authors.initials: V
authors.lastname: Iskersky
mesh_terms: D001724:Birth Weight; D002110:Caffeine / Q000008:administration & dosage*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D020345:Enterocolitis, Necrotizing / Q000453:epidemiology*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
chemical_list: D000697:Central Nervous System Stimulants; D014662:Vasoconstrictor Agents; D002110:Caffeine
keywords: Necrotizing enterocolitis; caffeine citrate; premature infants