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02-01-2012 | Legal medicine | Article

Ranitidine linked to adverse outcomes in very low birthweight newborns


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MedWire News: Ranitidine therapy is associated with an increased risk for infections, necrotizing enterocolitis (NEC), and mortality in very low birthweight (VLBW) newborns, Italian researchers say.

Ranitidine is a histamine H2-receptor antagonist prescribed in an off-label manner to inhibit gastric acid secretion in neonates as prophylaxis or for the treatment of ulcers and gastroesophageal reflux disease, explain Gianluca Terrin (University La Sapienza, Rome) and colleagues.

Writing in the journal Pediatrics, they say that the findings of their study indicate that ranitidine should be administered only after a careful consideration of the risk-benefit ratio.

Terrin et al conducted a multicenter prospective study of 274 infants with a birthweight of 401-1500 g or a gestational age of 24-32 weeks, who were consecutively observed in four neonatal intensive care units between January 2006 and June 2007.

Two cohorts of babies were evaluated: those treated with ranitidine (n=91) for stress-induced peptic disease and those not exposed to ranitidine (n=183). Demographic and clinical characteristics were similar between the cohorts.

Newborns treated with ranitidine had a significant 5.5-fold higher risk for infections including sepsis, pneumonia, and urinary tract infection than newborns who were not treated with ranitidine. The pathogens responsible for these infections include Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

Newborns treated with ranitidine also had a significant sixfold increased risk for NEC (defined as Bell stage >II) than those not treated with ranitidine, at 9.8% versus 1.6%. The authors note that the risk for NEC was unrelated to the dosage or duration of ranitidine therapy.

The rate of mortality was significantly higher in babies exposed to ranitidine, at 9.9%, compared with just 1.6% in babies who were not exposed to ranitidine.

Further analysis revealed that the length of hospital stay was significantly greater in newborns who received ranitidine than those who were not (52 vs 36 days).

The authors say that there are several mechanisms by which the inhibition of gastric acid secretion leads to infections, and suggest that the destruction of gastric juice and intestinal microflora, two of the major defense mechanisms against microorganism invasion of the gut, is a major aspect.

They add that hypochlorhydria induced by ranitidine could significantly alter the intestinal microflora, which may also contribute to the increased susceptibility to infection.

"Ranitidine should be administered with care in preterm infants because of the risk of severe infectious disease," recommend Terrin et al.

"Further studies are necessary to investigate the pathogenesis of these effects and the possible prophylactic measures that could be taken to prevent them."

By Piriya Mahendra

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