Hydroxyurea is generally contraindicated in patients with sickle cell disease who become or plan to become pregnant, but post-marketing safety data suggest that treatment continuation is safe.

The findings have important implications both for patients with accidental exposure and patients with limited treatment options, such as those with a history of a delayed hemolytic transfusion reaction (DHTR). Discontinuing hydroxyurea can pose serious risks in such patients, Anoosha Habibi, MD, reported during a plenary session at the American Society of Hematology (ASH) 2025 Annual Meeting.

Among more than 200 patients in the European Sickle Cell Disease Cohort-HydroxyUrea (ESCORT-HU) and ESCORT-HU Extension studies who became pregnant during or after hydroxyurea exposure, no maternal deaths occurred and no treatment-related malformations were observed among newborns, said Habibi, an associate professor in the Sickle Cell Referral Center, Hôpitaux Universitaires Henri Mondor, Creteil, France. 

“Hydroxyurea remains the only drug that significantly reduces mortality in sickle cell disease,” Habibi said.

However, teratogenic malformations have been reported at high doses of 150 mg/kg/day in animal studies, which is why patients are typically advised to discontinue treatment 3-6 months before conception or as soon as possible after conception, even though humans are treated with much lower doses, she noted.

For some patients, blood transfusions are a viable treatment alternative, but that’s not the case for those with a history of DHTR and those in low-resource settings where transfusions may not be available, Habibi explained.

Given the limitations of prior studies showing possible teratogenic risks, Habibi and colleagues assessed outcomes in patients from the ESCORT-HU and ESCORT-HU Extension studies. The prospective, multicenter, non-interventional cohort studies were conducted in France, Greece, Germany, and Italy as part of a post-marketing commitment to the European Medicines Agency following the agency’s approval of hydroxyurea for sickle cell disease.

During the studies, 245 pregnancies occurred in 183 patients. Of those, 207 (84%) were in patients receiving hydroxyurea. The mean dose was 16 mg/kg/day, and treatment was stopped during the first trimester in most cases. Nine patients with a history of DHTR were treated throughout pregnancy.

In 36 cases, hydroxyurea was stopped prior to pregnancy and was not reinitiated during pregnancy. Information about treatment was unavailable for two cases.

Mean hydroxyurea exposure duration before conception was 3.8 years in ESCORT-HU and 10.0 years in the extension study. 

Twenty-five pregnancies in the patients exposed to hydroxyurea during pregnancy resulted in voluntary abortion. Miscarriages occurred in 17% and 22% of patients in the hydroxyurea-exposed and non-exposed patient groups, respectively, which is comparable to the general population and lower than reported in previous studies, Habibi said.

Live births occurred in 74% of cases in both the exposed and non-exposed groups, and premature births occurred in 17% and 11% of cases in each group, respectively. 

One stillbirth occurred during the first month of pregnancy in an exposed patient but was not considered to be related to hydroxyurea exposure. Two therapeutic abortions due to life-threatening maternal complications were performed in the exposed group and one in the unexposed group.

No maternal deaths occurred despite the severity of sickle cell disease in the cohorts, Habibi noted. 

“The findings are very reassuring — accidental or early [hydroxyurea] exposure may be less dangerous than we once feared,” she said during a press briefing ahead of the ASH meeting. She stressed that there are potential implications for “low-income countries where blood transfusions are often limited and the safety not guaranteed.”

“In this setting, we have to ask: Is it riskier to continue hydroxyurea during pregnancy or to stop it and increase the risk of severe complications?” she explained, noting that these findings suggest hydroxyurea can be continued in such cases.

Additional studies with larger datasets are needed to better assess the effects of hydroxyurea exposure during pregnancy and long-term outcomes in exposed children, she concluded.

During the press briefing, moderator Titilope Fasipe, MD, PhD, applauded Habibi’s “call to action” for additional studies and long-term follow-up.

Fasipe, an associate professor of pediatrics at Baylor College of Medicine and co-director of the Sickle Cell Program at Texas Children’s Hospital, Houston, asked Habibi what she considered the “most important counseling point” for patients who become pregnant while taking hydroxyurea.

Habibi responded that her main points were to call for continuing treatment in patients with a history of DHTR and making treatment decisions on a case-by-case basis for all others as recommended by French guidelines.

Of note, ASH is currently developing new clinical practice guidelines on dosing and monitoring of hydroxyurea for sickle cell disease. The draft guidelines, which are available for public comment until January 20, 2026, similarly include proposed recommendations for “either continuing hydroxyurea or discontinuing hydroxyurea on a case-by-case basis with shared decision-making” both for individuals who are taking hydroxyurea and intending to conceive or who become pregnant while taking hydroxyurea. These proposed recommendations are based on a “very low certainty of evidence.”

Habibi has reported receiving research funding, honoraria, and/or consulting fees from Theravia, Novo Nordisk, and Pfizer.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on X: @SW_MedReporter.