Safety of Hydroxyurea in Pregnancy: A Systematic Review of the Literature

Hydroxyurea (HU) is an antimetabolite drug used to manage several hematologic conditions, including chronic myeloid leukemia and sickle cell disease (SCD). Animal studies and limited human data have raised concern that HU exposures in pregnancy may increase the risk of congenital malformations or abnormal fetal growth. Although the quality of evidence is low, it has been recommended that HU is discontinued at least 3 months before conception.

We systematically reviewed all published studies up to July 2024 describing pregnancy and neonatal outcomes after HU exposure during pregnancy.

A total of 329 articles went through title and abstract screening, which resulted in 54 articles undergoing full-text review, and 15 articles were finally eligible for data extraction. These 15 studies included in the review, published between 1993 and 2023, comprised 7227 pregnancies, with 567 pregnancies (7.8%) exposed to HU. Patient ages ranged from 17 to 45 years. Most patients had SCD (n = 502), followed by chronic myeloid leukemia (n = 26), essential thrombocythemia (n = 24), and chronic myeloid splenomegaly (n = 2). In 13 cases, the underlying disease was not specified. The timing of exposures to HU varied from conception until throughout pregnancy. Neither teratogenic nor hematologic effects on the fetus were observed in these cases.

Pregnancy risks associated with HU are lower than anticipated. The use of HU in pregnancy may be justified considering the significant risks associated to untreated conditions, such as SCD.