Ranitidine is associated with infections, necrotizing enterocolitis, and fatal outcome in newborns

Pediatrics. 2012 Jan;129(1):e40-5. doi: 10.1542/peds.2011-0796. Epub 2011 Dec 12.

Abstract

Background and objectives: Gastric acidity is a major nonimmune defense mechanism against infections. The objective of this study was to investigate whether ranitidine treatment in very low birth weight (VLBW) infants is associated with an increased risk of infections, necrotizing enterocolitis (NEC), and fatal outcome.

Methods: Newborns with birth weight between 401 and 1500 g or gestational age between 24 and 32 weeks, consecutively observed in neonatal intensive care units, were enrolled in a multicenter prospective observational study. The rates of infectious diseases, NEC, and death in enrolled subjects exposed or not to ranitidine were recorded.

Results: We evaluated 274 VLBW infants: 91 had taken ranitidine and 183 had not. The main clinical and demographic characteristics did not differ between the 2 groups. Thirty-four (37.4%) of the 91 children exposed to ranitidine and 18 (9.8%) of the 183 not exposed to ranitidine had contracted infections (odds ratio 5.5, 95% confidence interval 2.9-10.4, P < .001). The risk of NEC was 6.6-fold higher in ranitidine-treated VLBW infants (95% confidence interval 1.7-25.0, P = .003) than in control subjects. Mortality rate was significantly higher in newborns receiving ranitidine (9.9% vs 1.6%, P = .003).

Conclusions: Ranitidine therapy is associated with an increased risk of infections, NEC, and fatal outcome in VLBW infants. Caution is advocated in the use of this drug in neonatal age.

MeSH terms

  • Anti-Ulcer Agents / adverse effects*
  • Anti-Ulcer Agents / therapeutic use
  • Bacterial Infections / etiology*
  • Bacterial Infections / immunology
  • Enterocolitis, Necrotizing / chemically induced*
  • Female
  • Gastric Acid / metabolism
  • Histamine H2 Antagonists / adverse effects*
  • Histamine H2 Antagonists / therapeutic use
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / chemically induced*
  • Infant, Premature, Diseases / immunology
  • Infant, Premature, Diseases / mortality
  • Infant, Premature, Diseases / prevention & control
  • Infant, Very Low Birth Weight*
  • Male
  • Peptic Ulcer / prevention & control
  • Ranitidine / adverse effects*
  • Ranitidine / therapeutic use
  • Risk Factors

Substances

  • Anti-Ulcer Agents
  • Histamine H2 Antagonists
  • Ranitidine