Phenobarbitone for Prevention and Treatment of Unconjugated Hyperbilirubinemia in Preterm Neonates: A Systematic Review and Meta-analysis

Objective: To evaluate the role of phenobarbitone in the management of unconjugated hyperbilirubinemia during first two weeks of life in preterm neonates. Design: Meta-analysis. Methods: A study was eligible for inclusion in the meta-analysis if it randomized preterm neonates into control and treatment groups. Standard search strategy of the Cochrane Neonatal Review Group was used. For categorical and continuous data the odds ratio (OR) and weighted mean difference (WMD) were calculated, respectively. 95% confidence intervals were used and a fixed effects model was assumed for the meta-analysis. Main outcome measures: Peak serum bilirubin, duration of phototherapy, need of phototherapy and exchange transfusion, neurodevelopmental outcome and adverse effects. Results: A total of 19 potentially relevant studies were identified. Of these, 3 studies (497 neonates) were included in the meta-analysis. Peak serum bilirubin was significantly lower in phenobarbitone group (mean difference: -1.78 mg/dL, 95% CI: -2.29 to -1.27). Duration of phototherapy was shorter (mean difference: -14.75 h, 95% CI: -26.67 to -2.83). Need of phototherapy (OR: 0.33, 95% CI: 0.13 to 0.81) and exchange transfusion (OR: 0.30, 95% CI: 0.14 to 0.64) were also reduced in phenobarbitone group. Conclusion: Phenobarbitone reduces peak serum bilirubin, duration and need of phototherapy and need of exchange transfusion in preterm very low birthweight neonates. Further studies are warranted to evaluate adverse effects and neurodevelopmental outcome.