Iranian Journal of Neonatology

Iranian Journal of Neonatology

Phenobarbital Administration in Pregnancies Undergoing IUT Due to Rh Alloimmunization: A Single-Blinded Randomized Trial

Document Type : Original Article

Authors
Fatemeh Rahimi-Sharbaf 1
Sara Saeedi 1
Fatemeh gholshahi 1
Mahboobeh Shirazi 1
Behrokh Sahebdel 1
Mohamadreza Zarkesh 2
Mozhgan Sina 1
Arash Jafarieh 3
Sima Amini 1
Sania Saeedi 1
Sare Ezzati 1
Parisa Najjari 1
Golshan Manteghi 1
1 Maternal, Fetal and Neonatal Research Center, Yas Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Pediatrics, School of Medicine, Yas Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
3 Maternal, Fetal and Neonatal Research Center, Yas Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran Department of Anesthesiology, School of Medicine, Amir Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran
10.22038/ijn.2026.91234.2776
Abstract
Background: Red blood cell (RBC) alloimmunization and the ensuing hemolysis in hemolytic disease of the fetus and newborn (HDFN) result 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 reducing postnatal blood exchange transfusion and phototherapy.
Methods: This parallel-group, single-blind, randomized clinical trial with a control group was performed on 75 pregnant women undergoing intrauterine transfusion (IUT) for Rh alloimmunization. The trial is described as single-blinded (only the assessing pediatrician was blinded), and the control group received no placebo. Participants were randomly divided into intervention and control groups using the random allocation rule. 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 incidence of icterus 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 that phenobarbital prescription in the intervention group significantly (p < 0.001) decreased the 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.
Keywords
Exchange transfusion
Hemolytic disease of the fetus and newborn (HDFN)
Hyperbilirubinemia
Phenobarbital
Phototherapy
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Iranian Journal of Neonatology
Volume 17, Issue 4
Autumn 2026
Pages 39-45