|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 — the cessation of breathing during sleep. Dr. Higgins said
that this belief is controversial 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, because they are unable to feed unassisted,
must be fed through a tube inserted through the esophagus.
In the paper, Dr. Guillet and her coworkers hypothesized that, by decreasing
acidity in the digestive tract, H2 blockers might result in excessive levels
of a type of bacteria known as gram negative bacteria. These high bacterial levels,
in turn, might lead to necrotizing entercolitis. The gram negative bacteria,
normally harmless, are presumably kept in check by stomach acid, and might increase
to unhealthy levels in the absence of sufficient stomach acid.
In support of their hypothesis, the researchers cited a study which found that
experimental animals with reduced stomach acid levels had higher levels of gram
negative bacteria and a high likelihood of developing necrotizing enterocolitis.
The researchers also cited a study which found that premature infants fed human
milk with a slightly higher acidity level than normal had lower levels of gram
negative bacteria and were less likely to develop necrotizing enterocolitis than
were 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 whether premature infants given these drugs have an increased
likelihood of necrotizing enterocolitis.
The NICHD is part of the National Institutes of Health (NIH), the biomedical
research arm of the federal government. NIH is an agency of the U.S. Department
of Health and Human Services. The NICHD sponsors research on development, before
and after birth; maternal, child, and family health; reproductive biology and
population issues; and medical rehabilitation.
The National Institutes of Health (NIH) — The Nation's Medical Research
Agency — includes 27 Institutes and Centers and is a component of
the U. S. Department of Health and Human Services. It is the primary Federal
agency for conducting and supporting basic, clinical, and translational medical
research, and it investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.