Ibuprofen Use Linked to Hyperbilirubinemia in Preterm Infants

From Reuters Health Information

Jul 20 - Preterm infants who receive ibuprofen to prevent patent ductus arteriosus have more severe hyperbilirubinemia than their counterparts not given the drug, according to study findings in the August issue of Pediatrics.

Hyperbilirubinemia is thought to adversely affect neurodevelopmental outcomes in preterm infants, and in vitro evidence indicates that ibuprofen can displace bilirubin from albumin, the study authors note. The resulting rise in unbound bilirubin might increase the odds of kernicterus and encephalopathy.

In the current study, Dr. Enrico Zecca, from Universita Cattolica del Sacro Cuore, Rome, and colleagues assessed bilirubin levels and related outcomes in 418 infants who were treated with ibuprofen and in 288 infants not exposed to the drug.

Total serum bilirubin levels were higher in the ibuprofen group than in controls, the researchers found. Moreover, ibuprofen-treated infants were more likely to require phototherapy and did so for longer durations.

No significant differences were noted between the groups in gestational age, birthweight, gender ratio, the incidence of glucose-6-phosphate dehydrogenase deficiency, or hypoalbuminemia, the report shows. Hemolytic isoimmunization also occurred with similar frequency in each group. Lastly, the exchange-transfusion rates in each group were similar, hovering around 4.7%.

The authors believe that in addition to displacing bilirubin from albumin, ibuprofen may promote hyperbilirubinemia by competing with the enzyme responsible for bilirubin conjugation.

"This was a pragmatic study to advise clinicians to balance the benefits of ibuprofen against its possible side effects, among which more-pronounced hyperbilirubinemia, with a subsequent impact on global newborn care, should be considered carefully," the team writes.

Pediatrics 2009;124:480-484.