title: Safety of histamine-2 receptor blockers in hospitalized VLBW infants.
abstract: Histamine-2 receptor (H2) blockers are often used in very low birth weight infants despite lack of population specific efficacy and safety data.
  
  
  
  We sought to describe safety and temporal trends in histamine-2 receptor (H2) blocker use in hospitalized very low birth weight (VLBW) infants.
  
  
  
  We conducted a retrospective cohort study using a clinical database populated by an electronic health record shared by 348 neonatal intensive care units in the United States.
  
  
  
  We included all VLBW infants without major congenital anomalies.
  
  
  
  We used multivariable logistic regression with generalizing estimating equations to evaluate the association between days of H2 blocker exposure and risk of: 1) death or necrotizing enterocolitis (NEC); 2) death or sepsis; and 3) death, NEC, or sepsis.
  
  
  
  Of 127,707 infants, 20,288 (16%) were exposed to H2 blockers for a total of 6,422,352days. Median gestational age for infants exposed to H2 blockers was 27weeks (25th 75th percentile 26, 29). H2 blocker use decreased from 18% of infants in 1997 to 8% in 2012 (p<0.001). On multivariable analysis, infants were at increased risk of the combined outcome of death, NEC, or sepsis on days exposed to H2 blockers (odds ratio=1.14) (95% confidence interval 1.08, 1.19).
  
  
  
  H2 blocker use is associated with increased risk of the combined outcome of death, NEC, or sepsis in hospitalized VLBW infants.
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA. Electronic address: aromaine@live.unc.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Romaine
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA. Electronic address: daniel.ye@duke.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ye
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA. Electronic address: aosterrr@gmail.com.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Ao
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA. Electronic address: francia.fang@duke.edu.
authors.forename: Francia
authors.initials: F
authors.lastname: Fang
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA. Electronic address: octaviousjohnson33@yahoo.com.
authors.forename: Octavious
authors.initials: O
authors.lastname: Johnson
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA. Electronic address: tsblake015@gmail.com.
authors.forename: Taylor
authors.initials: T
authors.lastname: Blake
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA. Electronic address: danny.benjamin@dm.duke.edu.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Benjamin
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA. Electronic address: michael.cotten@duke.edu.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Cotten
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA. Electronic address: danielatestoni@gmail.com.
authors.forename: Daniela
authors.initials: D
authors.lastname: Testoni
authors.affiliation: Pediatrix-Obstetrix Center for Research and Education, Sunrise, FL,USA. Electronic address: Reese_H_Clark@us.MEDNAX.com.
authors.forename: Reese H
authors.initials: RH
authors.lastname: Clark
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA. Electronic address: vivian.chu@duke.edu.
authors.forename: Vivian H
authors.initials: VH
authors.lastname: Chu
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA. Electronic address: brian.smith@dm.duke.edu.
authors.forename: P Brian
authors.initials: PB
authors.lastname: Smith
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA. Electronic address: christoph.hornik@dm.duke.edu.
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Hornik
mesh_terms: D020345:Enterocolitis, Necrotizing / Q000453:epidemiology / Q000209:etiology; D005260:Female; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D007363:Intensive Care Units, Neonatal / Q000706:statistics & numerical data; D008297:Male; D012189:Retrospective Studies; D018805:Sepsis / Q000453:epidemiology / Q000209:etiology
chemical_list: D006635:Histamine H2 Antagonists
keywords: H2 blockers; Histamine-2 receptor antagonists; Infants; Necrotizing enterocolitis