Does Ibuprofen increase neonatal hyperbilirubinemia?

Objective: The aim of this study was to investigate whether ibuprofen exposure was associated with increased hyperbilirubinemia in preterm infants.

Methods: Since 2000, ibuprofen has been administered to all infants at <30 weeks of gestation who are admitted to our unit, to prevent patent ductus arteriosus. We retrospectively compared data for 418 infants subjected to ibuprofen prophylaxis (2000-2007) and 288 infants not exposed to ibuprofen (1993-1999).

Results: The ibuprofen group had a significantly higher peak total serum bilirubin level (9.0 +/- 2.5 mg/dL vs 7.3 +/- 3.3 mg/dL), more need for phototherapy (398 infants [95%] vs 254 infants [87.6%]), and a longer phototherapy duration (94.3 +/- 43.6 hours vs 87.2 +/- 38.6 hours). Groups did not differ with respect to gestational age, birth weight, gender ratio, glucose-6-phosphate dehydrogenase deficiency incidence, or hypoalbuminemia (<2.5 g/dL) incidence. Hemolytic isoimmunization was diagnosed with similar incidences (no-ibuprofen group: 7 of 288 infants; ibuprofen group: 8 of 418 infants). The rates of exchange-transfusion also were similar between the groups (no-ibuprofen group: 14 infants [4.8%]; ibuprofen group: 19 infants [4.5%]).

Conclusions: Ibuprofen administration was associated with higher peak total serum bilirubin levels, and the more-pronounced hyperbilirubinemia led to longer phototherapy. The potential role of competition between ibuprofen and bilirubin in the hepatic glucuronidation pathway is discussed.