Ursodeoxycholic acid and phototherapy versus phototherapy and placebo on neonatal indirect hyperbilirubinemia

Abstract

Introduction: Recently ursodeoxycholic acid was recommended for the treatment of neonatal hyperbilirubinemia in a few studies. Objectives: This study aimed to compare ursodeoxycholic acid and phototherapy versus phototherapy in lowering the level of bilirubin in neonates who was admitted due to hyperbilirubinemia. Patients and Methods: This randomized double-blind study was carried out in the department of neonatology at the children’s medical center of Ahvaz Jundishapur of the University of Medical Sciences. Inclusion criteria were weight 2500-4200 g and exclusive breastfeeding. Gestational age between 38-41 weeks and age between 3-7 days were included. Total bilirubin between 14-20 according to Bhutani nomogram and direct bilirubin was less than 2 mg/dl was included. Exclusion criteria were ABO incompatibility, Rh incompatibility, G6PD (glucose6-phosphate dehydrogenase) deficiency, sepsis, hypothyroidism, liver problem, prematurity and newborn of diabetic mothers. A dose of 5 mg/kg per dose of ursodeoxycholic acid (UDCA) was prescribed for neonates every 12 hours. Placebo is also prescribed for other neonates. Unconjugated bilirubin was measured after 4 hours and every 12 hours till total bilirubin=12 mg/dL. The primary outcome measures were total bilirubin level four hours and every 12 hours after admission till reached 12 mg/dL. The secondary outcome measure was total bilirubin=12 mg/dL at 12-24 hours after admission and diarrhea, vomiting, skin rash or any adverse effect in the neonates who received UDCA. Neonates who underwent phototherapy and UDCA were the case group. Neonates who received phototherapy and placebo were allocated in the control group. Data were analyzed using SPSS version 16.0. Kolmogorov-Smirnov test was conducted to evaluate data distribution. Intention-to-treat analysis was used. Mann-Whitney U test was conducted for data analysis. Results: In the current study, 30 cases and 30 control were included. Discharged neonates were 96% among the UDCA group and 87% among the control group in the 1st 24 hours after admission. Among the UDCA group, 100% were discharged at the 2nd 24 hours of admission and 96% among the control. The duration of phototherapy was shorter in the case group than in the control group, however this difference had no statistical difference. Conclusion: No significant difference between neonates who underwent phototherapy and phototherapy+ UDCA in terms of duration of phototherapy and bilirubin reduction was found. Trial Registration: The trial protocol was approved by the Iranian Registry of Clinical Trials (identifier: IRCT20181003041225N1; https://en.irct.ir/trial/34272, ethical code; IR.AJUMS.REC.1397.899).