Efficacy of oral phenobarbitone in term "at risk" neonates in decreasing neonatal hyperbilirubinemia: a randomized double-blinded, placebo controlled trial

Abstract

Objective: To evaluate the efficacy of oral phenobarbitone in "at risk " term neonates (with high cord bilirubin) in decreasing hyperbilirubinemia. Design: Double blind, placebo-control, randomized trial. Setting: Tertiary level neonatal unit. Outcome: Primary-hyperbilirubinemia defined as total serum bilirubin (TSB) greater than 13 mg/dL. Secondary–TSB at 72 ± 12 hr, need for phototherapy or exchange transfusion and side effects of phenobarbitone therapy. Methods: All consecutively born term healthy neonates with cord bilirubin ≥2.5 mg/dL were randomly assigned to receive either phenobarbitone (n = 37) or placebo (n = 38) after obtaining informed consent. Phenobarbitone was administered orally (5 mg/kg/day) for 3 days starting within 12 hours of birth. The neonates were followed up till seven days of life. TSB was estimated in neonates who developed jaundice with clinically assessed level of 8-10 mg/dL and at 72 ± 12 hours of age in 55 neonates. Results: The baseline characteristics were similar in two groups. There was no significant reduction in incidence of hyperbilirubinemia in phenobarbitone group compared to in placebo group (6/37 (16.2%) versus 13/38 (34.3%); RR 0.47, 95% confidence interval: 0.20-1.11; risk difference: -18.1%, 95% confidence interval: -39.5 to 3.3%). However TSB at 72 ± 12 hours in phenobarbitone group (mean ± S.D: 10.0 ± 3.7 mg/dL) was significantly lesser than in placebo group (mean ± S.D: 12.3 ± 3.3 mg/dL) (difference of means: –2.3 mg/dL, 95% confidence interval: –3.9 to –0.7 mg/dl, P = 0.018). No significant difference with respect to need for treatment was observed in two groups. No significant adverse effects of phenobarbitone were noted. Conclusions: Prophylactic phenobarbitone is not helpful in reducing the incidence of hyper-bilirubinemia in ‘at risk’ term neonates.