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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ARTICLE

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

     ABSTRACT
 TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES

 
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.

FREE FULLTEXT : PEDIATRIC JOURNAL AUGUST 2009

REFERENCES

  1. Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev. 2008;(1) :CD003481[Medline]
  2. Aranda JV, Varvarigou A, Beharry K, et al. Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant. Acta Pediatr. 1997;86 (3):289 –293[Web of Science][Medline]
  3. Van Overmeire B, Touw D, Schepens PJC, Kearns GL, van den Anker JN. Ibuprofen pharmacokinetics in preterm infants with patent ductus arteriosus. Clin Pharmacol Ther. 2001;70 (4):336 –343[Web of Science][Medline]
  4. Rasmussen LF, Ahlfors CE, Wennberg RP. Displacement of bilirubin from albumin by indomethacin. J Clin Pharmacol. 1978;18 (10):477 –481[Abstract]
  5. Kuehl GE, Lampe JW, Potter JD, Bigler J. Glucuronidation of non-steroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005;33 (7):1027 –1035[Abstract/Free Full Text]
  6. Ambat MTC, Ostrea EM Jr, Aranda JV. Effect of ibuprofen L-lysinate on bilirubin binding to albumin as measured by saturation index and horseradish peroxidase assays. J Perinatol. 2008;28 (4):287 –290[CrossRef][Web of Science][Medline]
  7. Ahlfors CE. Effect of ibuprofen on bilirubin-albumin binding. J Pediatr. 2004;144 (3):386 –388[CrossRef][Web of Science][Medline]
  8. Van Overmeire B. Ibuprofen, bilirubin and albumin: the importance of a balance. Eur J Pediatr. 2006;165 (suppl 1):113
  9. De Carolis MP, Romagnoli C, Polimeni V, et al. Prophylactic ibuprofen therapy of patent ductus arteriosus in preterm infants. Eur J Pediatr. 2000;159 (5):364 –368[CrossRef][Web of Science][Medline]
  10. Kazmierczak SC, Robertson AF, Catrou PG, Briley KP, Kreamer BL, Gourley GR. Direct spectrophotometry method for measurement of bilirubin in newborns: comparison with HPLC and an automated diazo method. Clin Chem. 2002;48 (7):1096 –1097[Free Full Text]
  11. Romagnoli C, Zecca E, Papacci P, Vento G, Girlando P, Latella C. Which phototherapy system is most effective in lowering serum bilirubin in very preterm infants? Fetal Diagn Ther. 2006;21 (2):204 –209[CrossRef][Web of Science][Medline]
  12. Dupont WD, Plummer WD. PS power and sample size program available for free on the Internet. Control Clin Trials. 1997;18 (3):274[CrossRef][Web of Science]
  13. Dupont WD, Plummer WD. PS power and sample size calculations: a review and computer program. Control Clin Trials. 1990;11 (2):116 –128[CrossRef][Web of Science][Medline]
  14. Ahlfors CE. Unbound bilirubin associated with kernicterus: a historical approach. J Pediatr. 2000;137 (4):540 –544[CrossRef][Web of Science][Medline]
  15. Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008;371 (9606):64 –74[CrossRef][Web of Science][Medline]
  16. Oh W, Tyson JE, Fanaroff AA, et al. Association between peak serum bilirubin and neurodevelopmental outcomes in extremely low birth weight infants. Pediatrics. 2003;112 (4):773 –779[Abstract/Free Full Text]
  17. Wennberg RP, Ahlfors CE, Bhutani VK, Johnson LH, Shapiro SM. Toward understanding kernicterus: a challenge to improve the management of jaundiced newborns. Pediatrics. 2006;117 (2):474 –485[Abstract/Free Full Text]
  18. Amin SB, Ahlfors CE, Orlando MS, Dalzell LE, Merle KS, Guillet R. Bilirubin and serial auditory responses in preterm infants. Pediatrics. 2001;107 (4):664 –670[Abstract/Free Full Text]
  19. Ahlfors CE, Herbsman O. Unbound bilirubin in a term newborn with kernicterus. Pediatrics. 2003;111 (5):1110 –1112[Free Full Text]
  20. Decobert F, Kampf F, Durrmeyer X, Danan C, Dassieu G. Efficiency of a double-dosed second ibuprofen course for the closure of patent ductus arteriosus in extremely premature infants E-PAS2008:5842.4. Available at: www.abstracts2view.com/pasa. Accessed June 19, 2009

 

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