H2 blockers linked to life-threatening bowel infection in premature infants

March 2006

Premature infants who are given H2 blockers, a common class of nonprescription drugs used to treat acid reflux, are slightly more likely to develop a potentially fatal bowel infection than infants who are not treated with the drugs, according to the NIH.

H2 blockers inhibit the production of stomach acid and may put premature infants at risk of necrotizing enterocolitis, according to a new study. Researchers said that it is not possible to tell from the study whether or not the drugs caused the condition; nonetheless, they advised caution with their use in preemies. Common H2 blockers are cimetidine, famotidine, ranitidine and nizatidine. The study was published in Pediatrics.

Necrotizing enterocolitis affects between 5% and 10% of infants born extremely prematurely, explained Ronnie Guillet, MD, PhD, of the University of Rochester in New York, a member institution of the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network.

With necrotizing enterocolitis, tissue lining the wall of the intestines dies, and the surviving tissue becomes swollen and inflamed, leaving the digestive tract unable to digest or transport food. In some cases, damage to the intestines may require the removal of portions of the intestines. In other cases, the damage is so severe that the infant dies. The cause of the disorder is unknown, according to a release from NIH.

Guillet and colleagues analyzed the records of more than 11,000 very low birth weight infants who had been treated at the NICHD Neonatal Research Network. Of these, 787 premature infants had developed necrotizing enterocolitis. The infants ranged in weight from 401 g to 1,500 g. The researchers found that infants who received H2 blockers were 1.71 times more likely to develop necrotizing enterocolitis than infants who had not received them, according to the study.

No other studies have been conducted in large numbers of premature infants receiving H2 blockers, said program scientist Rosemary Higgins, MD, of the NICHD’s Pregnancy and Perinatology Branch.

Guillet and colleagues said that it was not possible to determine from the analysis whether or not H2 blockers cause necrotizing enterocolitis. Another possibility, they said, was that infants likely to develop necrotizing enterocolitis might also have symptoms that require H2 blockers. The records did not say why physicians prescribed the drugs. However, the practice is widespread in neonatal ICUs around the country.

Prescribing H2 blockers

Physicians prescribe H2 blockers to premature infants for several reasons, Higgins said. If premature infants are frequently experiencing acid reflux, physicians may prescribe the drugs to prevent damage to the esophagus.

Higgins added that some physicians may prescribe H2 blockers to premature infants who are not experiencing acid reflux out of concern that excessive stomach acid may lead to stomach ulcers. Other physicians believe that acid reflux may predispose infants to apnea. This belief is controversial, Higgins said, and no research has been conducted to determine its validity. In other cases, physicians may prescribe H2 blockers to prevent excess stomach acidity among infants who must be fed through a tube inserted through the esophagus.

Guillet and colleagues hypothesized that by decreasing acidity in the digestive tract, H2 blockers might result in excessive levels of gram-negative bacteria. These high bacterial levels, in turn, might lead to necrotizing entercolitis. Gram-negative bacteria, normally harmless, are presumably kept in check by stomach acid, and may increase to unhealthy levels in the absence of sufficient stomach acid.

In support of their hypothesis, the researchers cited two studies. The first study found that animals with reduced stomach acid levels had higher levels of gram-negative bacteria and a high likelihood of developing necrotizing enterocolitis. The second study found that premature infants fed human milk with a slightly higher acidity level had lower levels of gram-negative bacteria and were less likely to develop necrotizing enterocolitis than infants fed milk with a normal acidity level.

The researchers did not study any other drugs used to reduce stomach acidity, and do not know if premature infants who are given these drugs have an increased likelihood of necrotizing enterocolitis.

For more information:

• Guillet R, Stoll BJ, Cotton CM, et al. Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics. 2006;117:e137-e142.
• Patole S. Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis: a case of excessive collateral damage? Pediatrics. 2006;117:531-532.
• Crissinger KD. Animal models of necrotizing enterocolitis. J Pediatr Gastroenterol Nutr. 1996;20:17-22.
• Carrion V, Egan EA. Prevention of neonatal necrotizing enterocolitis. J Pediatr Gastroenterol Nutr. 1990;11:317-323.