Safety of histamine-2 receptor blockers in hospitalized VLBW infants

Early Hum Dev. 2016 Aug:99:27-30. doi: 10.1016/j.earlhumdev.2016.05.010. Epub 2016 Jul 4.


Background: Histamine-2 receptor (H2) blockers are often used in very low birth weight infants despite lack of population specific efficacy and safety data.

Aims: We sought to describe safety and temporal trends in histamine-2 receptor (H2) blocker use in hospitalized very low birth weight (VLBW) infants.

Study design: 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.

Subjects: We included all VLBW infants without major congenital anomalies.

Outcome measures: 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.

Results: 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).

Conclusions: H2 blocker use is associated with increased risk of the combined outcome of death, NEC, or sepsis in hospitalized VLBW infants.

Keywords: H2 blockers; Histamine-2 receptor antagonists; Infants; Necrotizing enterocolitis.

Publication types

  • Multicenter Study

MeSH terms

  • Enterocolitis, Necrotizing / epidemiology
  • Enterocolitis, Necrotizing / etiology
  • Female
  • Histamine H2 Antagonists / administration & dosage
  • Histamine H2 Antagonists / adverse effects*
  • Humans
  • Infant
  • Infant Mortality*
  • Infant, Newborn
  • Infant, Very Low Birth Weight*
  • Intensive Care Units, Neonatal / statistics & numerical data
  • Male
  • Retrospective Studies
  • Sepsis / epidemiology
  • Sepsis / etiology


  • Histamine H2 Antagonists