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.

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