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Increased Total Serum Bilirubin Level Post-Ibuprofen Use Is Inversely Correlated with Neonates' Body Weight
Zon-Min Lee1,2, Yao-Hsu Yang3,4,5, Ling-Sai Chang6
1Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.
Insights
Ibuprofen use increases total serum bilirubin (TSB) levels in neonates, particularly those with lower birth weights (BW). For extremely low birth weight (ELBW) infants with severe hyperbilirubinemia, intravenous acetaminophen is a safer alternative for treating patent ductus arteriosus (PDA).
Area of Science:
- Neonatal Medicine
- Pharmacology
- Bilirubin Metabolism
Background:
- Certain drugs can displace bilirubin from albumin, potentially causing hyperbilirubinemia in newborns.
- Ibuprofen is frequently used for patent ductus arteriosus (PDA) in neonates, but its effect on bilirubin levels is debated.
Purpose of the Study:
- To investigate the influence of ibuprofen on total serum bilirubin (TSB) levels in neonates across different birth weight (BW) categories.
- To identify safer alternatives for PDA treatment in neonates with hyperbilirubinemia.
Main Methods:
- Retrospective study of neonates (including premature infants) from January 2004 to July 2020.
- Analyzed TSB changes post-ibuprofen administration, correlating with phototherapy's effectiveness.
- Excluded neonates receiving ceftriaxone, with intraventricular hemorrhage, or TORCH infections.
Main Results:
- Phototherapy was more effective in reducing TSB in neonates with BW ≥ 1.5 kg compared to those < 1.5 kg.
- Ibuprofen use was associated with a significant increase in TSB, with the rise being greater in neonates with lower BW (p = 0.026).
- Neonates < 1 kg showed the highest average TSB increase (3.38 ± 2.77 mg/dL) post-ibuprofen.
Conclusions:
- Ibuprofen administration correlates with increased TSB levels in neonates, especially those with lower birth weights (< 1 kg).
- Intravenous acetaminophen is a suitable alternative to ibuprofen for treating PDA in extremely low birth weight (ELBW) neonates experiencing severe unconjugated hyperbilirubinemia.
Abstract:
Backgrounds: Drugs with the ability to displace bilirubin from albumin-binding sites subsequently leading to an increased bilirubin level may cause hyperbilirubinemia in neonates. Ibuprofen is commonly used to treat patent ductus arteriosus (PDA) in neonates, yet the use of ibuprofen has drawn mixed conclusions. We performed a retrospective study to determine how ibuprofen use influences the total serum bilirubin (TSB) level in neonates of differing birth weight (BW). Materials and methods: Neonates (including premature infants) born at Chang Gung Memorial Hospital, Taiwan during January 2004 to July 2020 were entered into this study. We recorded the phototherapy duration, including the initial day and end day, and determined the average influence of one-day phototherapy on TSB level. The highest monitored TSB level post-ibuprofen use minus the one measured prior to ibuprofen use was considered the TSB change following ibuprofen administration in this study, and the above-mentioned influence of daily phototherapy on the TSB level was used to correlate the results. Neonates with any of the following conditions were excluded: those who received ceftriaxone, those with intraventricular hemorrhage, and those infected with TORCH. Results: The average daily influence of phototherapy on the TSB level of neonates was −0.20 (−0.57~0.05) mg/dL, −0.28 (−0.84~0.13) mg/dL, −0.75 (−1.77~0.10) mg/dL, and −1.60 (−2.70~−0.50) mg/dL in neonates with BWs of <1 kg, 1−1.49 kg, 1.5−2.49 kg, and ≥2.5 kg, respectively, indicating that neonates with a BW ≥ 1.5 kg experienced a greater reduction in TSB level following phototherapy as compared with those with a BW < 1.5 kg. The average TSB increase following ibuprofen use in neonates was 3.38 ± 2.77 mg/dL, 2.04 ± 2.53 mg/dL, and 1.34 ± 2.24 mg/dL in neonates with BWs of <1 kg, 1−1.49 kg, and ≥1.5 kg, respectively, i.e., an elevated TSB change with a decreased neonate BW was noted post-ibuprofen use (p = 0.026, one-way analysis of variance (ANOVA)). Conclusions: As ibuprofen use is correlated with an apparent increase in TSB level in neonates with a lower BW, especially in those with a BW < 1 kg, iv acetaminophen can be an appropriate alternative to ibuprofen for ELBW neonates for the treatment of PDA if they are experiencing severe unconjugated hyperbilirubinemia.
