Background: Red Blood Cell (RBC) alloimmunization and the ensuing hemolysis in the hemolytic disease of the fetus and newborn (HDFN) results in significant prenatal and postnatal mortality and morbidity through severe fetal anemia and hyperbilirubinemia. Phenobarbital induces hepatic enzymes involved in bilirubin metabolism. This study aimed to assess the effect of maternal phenobarbital administration on the reduction of postnatal blood exchange transfusion and phototherapy.

Methods: This clinical trial with a control group, with parallel groups, single-blind, randomized was performed on 75 pregnant women undergoing intrauterine transfusion (IUT) for Rh alloimmunization. The trial is described as single-blinded (only the assessing pediatrician blinded), and the control group received no placebo. Participants were randomly (using the Random allocation rule) divided into intervention and control groups. The intervention group received 30 mg of phenobarbital three times daily from ten days prior to the estimated due date until actual delivery. The women were followed up until delivery to assess pregnancy outcomes including icterus incidence or need for postnatal phototherapy or exchange transfusion.

Results: The first total bilirubin in the intervention group was significantly (p < 0.001) lower than that in the control group (4.99 ± 1.39 vs. 10.52 ± 5.88). The study outcomes, including icterus (p < 0.001), need for phototherapy (p < 0.001), and exchange transfusion (p < 0.001), were significantly lower in the intervention group. Logistic regression analysis showed phenobarbital prescription in the intervention group can significantly (P <0.001) decreased need for exchange transfusion by 94%.

Conclusion: This trial indicates the efficacy of late-gestation maternal phenobarbital (as a safe and low-cost intervention) in reducing postnatal hyperbilirubinemia and the need for phototherapy and exchange transfusion in neonates with severe Rh alloimmunization treated by IUT.