This article aims to explore the medication strategy for the treatment of type Ⅱ Crigler-Najjar syndrome (CNS II) during pregnancy with phenobarbital, focusing on the relationship between treatment dosage, treatment duration, and gestational stage of the patient with maternal and neonatal outcomes, providing a reference for the treatment of this rare disease during pregnancy.

: This study systematically searched the PubMed, Embase, Web of Science, and Cochrane Library database using the keywords “Pregnancy” and “Crigler-Najjar syndrome Ⅱ” with the logical connector “and”. The time range covered from the establishment of the database to March 2025. A total of 11 articles were screened.

A total of 11 patients with CNS Ⅱ during pregnancy were included. Among them, 3 cases did not receive drug treatment, and 2 cases had known total bilirubin levels, which were 7 mg·dL^-1 and 8.5 mg·dL^-1, respectively. Among the 3 cases, 1 newborn was healthy, 1 had jaundice that could subside on its own, and 1 had jaundice that required ursodeoxycholic acid treatment. The total bilirubin levels of the remaining 8 cases were between 6.85 and 21.5 mg·dL^-1, and all received phenobarbital treatment, with a dosage of 25-60 mg·d^-1. After treatment, 1 out of 8 newborns was completely healthy, 4 had varying degrees of jaundice, and all received 1-3 days of phototherapy and recovered. Follow-up was conducted for 6 months to 11 years for 3 of the infants, and no neurological damage was observed. During the treatment process, 5 patients received bilirubin level monitoring, once a week in the first month and once a month thereafter.

The current evidence suggests that the maternal bilirubin level may be one of the key factors influencing the neonatal outcome. When the bilirubin level remains above 8-10 mg·dL^-1, some studies recommend considering drug intervention under multidisciplinary assessment. However, due to the extremely small sample size and the lack of controlled studies, the causal relationship between the use of phenobarbital and maternal and infant outcomes cannot be clearly determined. The clinical benefits of phenobarbital use still need to be verified by more research. After thorough assessment by the treatment team, if phenobarbital intervention is chosen, it can be started in the early stage of pregnancy and continued until delivery, with a recommended dose of less than 60 mg·d^-1. During the treatment period, the maternal total bilirubin concentration should be closely monitored, once a week in the first month and once a month thereafter, to ensure the safety of medication.