"As pediatricians and neonatalogists, it's important for us to know whether the benefit of these drugs outweighs the potential for complications for these medically fragile children," said Sanjiv Amin, M.D., assistant professor of Pediatrics at the University of Rochester Medical Center and author of an article on the subject. "In the case of the tocolytic agent indomethacin, we know it impacts blood flow but there have been no large randomized studies to evaluate the effects on the baby."
Dozens of studies have been done, but none have had a large sample size or a definitive outcome on the effects of indomethacin. The new analysis of a collection of studies, or a metaanalysis, by University of Rochester Medical Center researchers pulls together enough data to conclude that there is an association between use of indomethacin and babies experiencing periventricular leukomalacia (white matter injury by decreasing blood flow in the brain, which may lead to cerebral palsy).
The analysis also showed an association between indomethacin and necrotizing entercolitis (a condition in which intestinal tissue dies, which can sometimes be successfully treated with antibiotics but can require surgery and even cause death), especially for those babies who were exposed to the drug within days of birth. However, use of antenatal indomethacin is not associated with intraventricular hemorrhage (bleeding in the brain), patent ductus arteriosus (a congenital heart defect), respiratory distress syndrome (a life-threatening lung disorder) or death.
Obstetricians often use indomethacin only when women go into labor extremely early. But many obstetricians believe it is more effective and has fewer side effects for the mother than other commonly used tocolytic agents, and so they may use it for woman whose babies are farther along.
Christopher Glantz, MD, MPH, professor of Obstetrics and Gynecology at the University of Rochester Medical Center and a co-author of the paper, said he hopes the analysis will encourage obstetricians to use the drug only when women are in labor very early when their babies are at most risk of the problems related to prematurity.
"It's important for us to realize that these drugs are not benign," Glantz said. "None of the drugs we have to stop labor work all that well, and we're stuck between a rock -- a premature baby who could benefit from more time in the womb -- and a hard place -- a baby who may develop problems because of drugs such as indomethacin that may provide extra time in the womb.
"We need to use the drug only on those who need it most."