Does Ibuprofen Increase Neonatal Hyperbilirubinemia?

PEDIATRICS Vol. 124 No. 2 August 2009, pp. 480-484 (doi:10.1542/peds.2008-2433)

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Does Ibuprofen Increase Neonatal Hyperbilirubinemia?

Enrico Zecca, MD, Costantino Romagnoli, MD, Maria Pia De Carolis, MD, Simonetta Costa, MD, Rosa Marra, MD and Daniele De Luca, MD


Division of Neonatology, Department of Pediatrics, University Hospital “A. Gemelli,” Catholic University of the Sacred Heart, Rome, Italy


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.



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