Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants

Pediatrics. 2006 Feb;117(2):e137-42. doi: 10.1542/peds.2005-1543. Epub 2006 Jan 3.


Objective: We sought to determine if an association exists between the use of histamine-2 receptor (H2) blockers and the incidence of necrotizing enterocolitis (NEC) in infants of 401 to 1500 g in birth weight.

Study design: Data from the National Institute of Child Health and Human Development Neonatal Research Network very low birth weight (401-1500 g) registry from September 1998 to December 2001 were analyzed. The relation between the diagnosis of NEC (Bell stage II or greater) and antecedent H2-blocker treatment was determined by using case-control methodology. Conditional logistic regression was implemented, controlling for gender, site of birth (outborn versus inborn), Apgar score of < 7 at 5 minutes, and postnatal steroids.

Results: Of 11072 infants who survived for at least 12 hours, 787 (7.1%) developed NEC (11.5% of infants 401-750 g, 9.1% of infants 751-1000 g, 6.0% of infants 1001-1250 g, and 3.9% of infants 1251-1500 g). Antecedent H2-blocker use was associated with an increased incidence of NEC (P < .0001).

Conclusions: H2-blocker therapy was associated with higher rates of NEC, which is in agreement with a previous randomized trial of acidification of infant feeds that resulted in a decreased incidence of NEC. In combination, these data support the hypothesis that gastric pH level may be a factor in the pathogenesis of NEC.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Case-Control Studies
  • Enterocolitis, Necrotizing / chemically induced*
  • Female
  • Histamine H2 Antagonists / adverse effects*
  • Histamine H2 Antagonists / therapeutic use
  • Humans
  • Infant, Newborn
  • Infant, Very Low Birth Weight*
  • Male


  • Histamine H2 Antagonists