Research Summary

Outcomes of Hydroxyurea-Exposed Pregnancies in Sickle Cell Disease

Edited by:
Ashton L. Stahl

Key Highlights

  • Prospective data from the ESCORT-HU and ESCORT-HU Extension cohorts tracked 246 pregnancies in women with sickle cell disease.
  • Most pregnancies (87%) were exposed to hydroxyurea at conception, and treatment was often discontinued in the first trimester.
  • No hydroxyurea-related newborn malformations were reported.
  • The live birth rate reached 76% in hydroxyurea-exposed pregnancies.

A new analysis from the ESCORT-HU and ESCORT-HU Extension cohort studies provides updated evidence regarding pregnancy outcomes in women with sickle cell disease (SCD) treated with hydroxyurea. The prospective multinational cohorts, conducted across France, Greece, Germany, and Italy, aimed to clarify potential maternal and fetal risks associated with hydroxyurea exposure, particularly given longstanding concerns about teratogenicity and the current recommendation to discontinue the drug prior to conception. Researchers presented their study results at the 67th ASH Annual Meeting and Exposition in Orlando, FL.

ESCORT-HU (2009–2019) and its Extension (2020–2025) are prospective, multicenter, non-interventional observational cohorts established to monitor the long-term safety of hydroxyurea in adults and children with SCD. Pregnancies were documented regardless of hydroxyurea status, and outcomes were classified as live births, non-live births, or ongoing at data cutoff. Investigators recorded hydroxyurea exposure duration, timing of drug discontinuation when applicable, maternal age, and pregnancy outcomes, including miscarriage, prematurity, fetal death, and the need for transfusion support.

Study Findings

Among 3145 enrolled patients, 246 pregnancies occurred in 202 women; the mean maternal age was 31.3 years. Hydroxyurea exposure at conception was common: 213 pregnancies (87%) occurred under treatment, with a mean dose of 16.5 mg/kg/day. In most cases, hydroxyurea was discontinued during the first trimester. Only 30 pregnancies involved hydroxyurea discontinuation before conception.

Of the 172 evaluable hydroxyurea-exposed pregnancies, 131 (76%) resulted in live births, with 27% classified as premature and 16% ending in miscarriage. The study recorded 2 fetal deaths and 2 medically indicated pregnancy terminations. No maternal deaths occurred. Among pregnancies in which hydroxyurea had been stopped prior to conception, outcomes included 19 normal births, 1 premature birth, and 9 miscarriages. Across all cohorts, no newborn malformations were attributed to hydroxyurea exposure. Transfusion support was required in 41% of pregnancies.

Clinical Implications

According to the study authors, these prospective data suggest that fertility appears preserved among women receiving hydroxyurea, and no hydroxyurea-specific adverse neonatal outcomes have been identified to date. The findings also indicate that a substantial proportion of pregnancies occurred while on treatment, reflecting a high rate of unplanned conception in this population. Authors note that while discontinuation of hydroxyurea remains the recommendation for planned pregnancies, continuation may be necessary when transfusion is not a viable alternative, particularly for patients with a history of delayed hemolytic transfusion reactions.

Expert Commentary

“Hydroxyurea may be continued when transfusion is not an alternative, particularly in patients with a history of delayed hemolytic transfusion reactions. Further studies with larger datasets are needed to better assess hydroxyurea exposure during pregnancy and the long-term outcomes in exposed children,” the researchers concluded.

Reference

Habibi A, Etienne-Julan M, Dimopoulou M, et al. Outcomes of pregnancies in sickle cell patients treated with hydroxyurea: Findings from the ESCORT-HU cohort studies. Presented at: 67th ASH Annual Meeting and Exposition in Orlando, FL. December 7, 2025. https://submit.hematology.org/program/presentation/681292