HYDROXYUREA pregnancy exposure remains a major clinical dilemma in sickle cell disease (SCD), balancing maternal disease control against uncertain fetal risk. New prospective data from the ESCORT-HU programme, presented at the American Society of Hematology (ASH) 2025 Annual meeting, provides the most detailed European picture to date, offering cautious reassurance for clinicians managing women of reproductive age with severe SCD.
Real-World Hydroxyurea Pregnancy Exposure Is Common
The ESCORT-HU (European Sickle Cell Disease COhoRT-HydroxyUrea) and ESCORT-HU Extension studies followed 3,145 patients, with 1412 (45%) men and 1733 (55%) women, two thirds aged 15 to 49, across 77 centres in France, Greece, Germany and Italy, capturing pregnancy outcomes prospectively regardless of treatment interruption. Among 202 women, 246 pregnancies were recorded, with nearly nine in ten occurring while patients were receiving hydroxyurea.
The high proportion of hydroxyurea pregnancy exposure highlights a key clinical reality: unplanned pregnancies are frequent in this population. Median exposure before conception ranged from almost four years in the original cohort to a decade in the extension study, reflecting long-term reliance on disease-modifying therapy.
Pregnancy Outcomes Under Hydroxyurea
Of the 213 pregnancies exposed to hydroxyurea, most women discontinued treatment during the first trimester, in line with current guidance. Among pregnancies with known outcomes, 76% resulted in live births. Prematurity occurred in 27% of cases, and miscarriage in 16%, rates that clinicians will recognise as broadly consistent with severe SCD rather than clearly drug-specific effects.
Importantly, no congenital malformations were reported as being related to hydroxyurea exposure. There were no maternal deaths, despite the inclusion of patients with significant disease severity, and transfusion support was required in 41% of pregnancies.
Outcomes among women who stopped hydroxyurea before conception were broadly similar, although numbers were smaller and miscarriage remained common.
Making Sense of Molecular Risk for Clinicians
Hydroxyurea is teratogenic in animal models, raising understandable concern. However, human data have remained sparse and conflicting. These findings do not prove safety, but they suggest that any teratogenic signal, if present, is not strong or frequent. For clinicians, this shifts the discussion from theoretical molecular risk to pragmatic, individualised risk–benefit assessment.
Implications For Clinical Practice
Current recommendations to discontinue hydroxyurea when pregnancy is planned remain appropriate. However, these data support consideration of continued hydroxyurea pregnancy exposure when transfusion is not a safe alternative, such as in women with prior delayed haemolytic transfusion reactions.
The authors rightly emphasise the need for larger datasets and long-term follow-up of exposed children. For now, ESCORT-HU offers valuable reassurance and supports shared decision-making grounded in real-world evidence rather than assumption alone.
Reference
Habibi A et al. Outcomes of pregnancies in sickle cell patients treated with hydroxyurea: Findings from the escort-HU cohort studies. Abstract 25-8632. ASH Annual Meeting, December 6-9 2025.
