Common Reflux Treatment Linked to Life Threatening Bowel Infection in Premature Infants
Researchers in an NIH network have found that premature infants given a common class of non-prescription drugs used to treat acid reflux are slightly more likely to develop a potentially fatal bowel disorder than are infants who are not treated with the drugs.
The drugs, known as H2 blockers, inhibit the production of stomach acid and may put premature infants at risk of necrotizing enterocolitis, a serious inflammation of the intestines. The study appears in the February 2006 Pediatrics and was conducted by researchers in the NIH's National Institute of Child Health and Human Development Neonatal Research Network.
The researchers pointed out that it is not possible to tell from the study whether or not the drugs caused the condition, but nonetheless advised caution with their use for premature infants.
"This study strongly suggests that the current practice of prescribing H2 blockers to prevent or treat acid reflux in premature infants needs to be carefully reevaluated by all concerned in light of these new findings," said Elias A. Zerhouni, M.D., Director of the National Institutes of Health.
Necrotizing enterocolitis affects from 5 to 10 percent of infants born extremely prematurely, explained the study's first author, Ronnie Guillet, M.D., Ph.D., of the University of Rochester in Rochester, New York, a member institution of the NICHD Neonatal Research Network.
With necrotizing enterocolitis, tissue lining the wall of the intestines dies. The surviving tissue becomes swollen and inflamed, and the digestive tract is unable to digest or transport food. In some cases, damage to the intestines may require that portions of the intestines be removed. In other cases, the damage is so severe that the infant dies. The cause of the disorder is unknown.
Common H2 blockers are cimetidine (Tagamet), famotidine (Pepcid), ranitidine (Zantac), and nizatidine (Axid).
To conduct the study, Dr. Guillet and her coworkers analyzed the records of more than 11,000 very low birth weight infants who had been treated in the NICHD Neonatal Research Network. Of these, 787 premature infants had developed necrotizing enterocolitis. The infants ranged in weight from 401 grams to 1500 grams (about 14 ounces to just over 3 lbs). The researchers found that infants who received H2 blockers were 1.71 times more likely to develop necrotizing enterocolitis than were infants who had not received them.
In their article, Dr. Guillet and her coauthors wrote that it is not possible to determine from the analysis whether or not H2 blockers cause necrotizing enterocolitis. Another possible explanation, they wrote, is that infants likely to develop necrotizing enterocolitis might also have symptoms that require treatment with H2 blockers. The records that the researchers analyzed did not contain information on why physicians prescribed the drugs.
No other studies have been conducted on large numbers of premature infants receiving H2 blockers, said the program scientist of the NICHD Neonatal Research Network, Rosemary Higgins, M.D., of NICHD's Pregnancy and Perinatology Branch. However, the practice is widespread in neonatal intensive care units around the country.
Physicians prescribe H2 blockers to premature infants for several reasons, Dr. Higgins said. If premature infants are experiencing a lot of acid reflux, physicians might prescribe the drugs to prevent damage to the esophagus.
Dr. Higgins added that some physicians may prescribe H2 blockers to a premature infant who is not experiencing reflux out of concern that excessive stomach acid may lead to stomach ulcers. Some physicians believe that reflux may predispose an infant to apnea