December 06, 2025
3 min read
Key takeaways:
Table of Contents
- Three-quarters of women who became pregnant during hydroxyurea therapy had live births.
- Researchers observed no detrimental effects on maternal or newborn health attributed to hydroxyurea.
ORLANDO — Hydroxyurea does not affect fertility among women with sickle cell diseaseaccording to study results presented at ASH Annual Meeting and Exposition.
The agent also does not appear to impact newborn health, findings showed.
Data derived from Habibi A, et al. Abstract 2. Presented at: ASH Annual Meeting and Exposition; Dec. 6-9, 2025; Orlando.
“As more people with sickle cell disease use hydroxyurea, we are seeing more pregnancies among women exposed to this medication,” Againosha Habibi, MD, associate professor at the Coordinating Referral Center for Sickle Cell Disease and Red Blood Cell Disorders at Paris-East Créteil University in France, said during a press conference. “Even though most women in our study had severe disease, 245 pregnancies occurred without any maternal death or fetal malformation linked to hydroxyurea, which is very reassuring. This suggests accidental or early exposure may be less dangerous than once feared.”
Hydroxyurea — an antimetabolite designed to prevent formation of sickle-shaped red blood cells — is approved for use in the United States for patients aged older than 2 years.
The agent helps prevent vaso-occlusive crises and acute chest syndrome, and it also can reduce the need for transfusions or hospitalization.
Prior research conducted in animals showed hydroxyurea crosses the placenta barrier and can cause teratogenicity, though those studies have used doses up to five times higher than typically administered to humans, Habibi said.
Due to concerns about these risks, women with sickle cell disease who intend to become pregnant often are encouraged to stop hydroxyurea therapy 3 to 6 months prior to conception, Habibi said. However, whether hydroxyurea could contribute to birth defects in a developing fetus or affect maternal outcomes had not been clearly established.
“The question is, are these teratogenic risks overestimated in humans?” Habibi said.
Habibi and colleagues evaluated data from two prospective, multicenter postmarketing studies of hydroxyurea conducted in Europe.
The studies — ESCORT-HU, conducted from 2009 to 2019, and ESCORT-HU Extension, conducted from 2020 through 2025 — had been designed to assess long-term safety of the agent for children and adults, with a focus on poorly understood risks.
Each study prospectively documented all pregnancies.
These studies included 3,145 patients (55% women; n = 1,733) treated at one of 77 centers in France, Germany, Greece or Italy. About 45.2% (n = 785) of the females enrolled were of child-bearing age.
Researchers documented 245 pregnancies among 183 women, with a mean maternal age at pregnancy of 30.7 years (± 5 years).
Median hydroxyurea exposure duration prior to conception reached 3.8 years (range, 1.6-6.6) in ESCORT-HU and 10 years (range, 6.1-13.8) in ESCORT-HU-Extension, and transfusion support during pregnancy had been provided during 41% of pregnancies.
In 36 cases, hydroxyurea treatment had been interrupted prior to pregnancy and was not resumed during pregnancy. Data were unavailable for two patients.
The other 207 pregnancies (84.4% of total) occurred during hydroxyurea therapy — indicating a high rate of unplanned pregnancies, according to investigators — with mean hydroxyurea dose at pregnancy of 16 mg/kg per day.
In most cases, women discontinued hydroxyurea during the first trimester.
Twenty-five pregnancies (12%) among hydroxyurea-exposed women ended with voluntary abortions and two were terminated for medical reasons.
Among the remaining 180 pregnancies among hydroxyurea-exposed women, results showed 134 live births (74.4%) — 31 (17%) of which were premature births — and 36 miscarriages (17%), with most miscarriages occurring during the first trimester.
Researchers reported one stillbirth, noting the 34-year-woman had been exposed to hydroxyurea only in the first month of pregnancy.
No maternal deaths had been reported. Researchers reported one congenital malformation — a case of hydronephrosis — that occurred in a newborn delivered by a woman exposed to hydroxyurea during the first 2 weeks of pregnancy; however, this was deemed unrelated to the medication.
Twenty-six (74%) of the 36 pregnancies among women who stopped hydroxyurea prior to pregnancy resulted in live births. Four premature births (11%) and eight miscarriages (22%) occurred.
The findings suggest most pregnancies that occur during hydroxyurea treatment result in live births and that — although hydroxyurea discontinuation is recommended — treatment may be continued when transfusion is not an option, researchers concluded.
“For some patients, stopping hydroxyurea is not possible due to history of delayed hemolytic transfusion reaction,” Habibi said. “It also is important to note that, in some low- to middle-income countries, access to blood transfusions is limited and safety is not guaranteed. In these settings, we have to ask if it is riskier to consider hydroxyurea during pregnancy or to stop it and increase risk of serious complications.”
Additional research based on data from larger cohorts will be necessary to better understand the extent of hydroxyurea exposure during pregnancy, Habibi said.
“We also need more long-term follow-up of exposed children, as well as more data from resource-limited settings,” she said.
For more information:
Anoosha Habibi, MD, can be reached at anoosha.habibi@aphp.fr.
Perspective
Decades ago, many people with sickle cell disease died before they reached their 30s. Today, pediatric hematologists are doing such a terrific job taking care of children with sickle cell disease that many more of them are living well into their child-bearing years. They also are growing up without as many medical complications because of hydroxyurea’s benefits.
However, hydroxyurea originally started being used in medicine as a traditional chemotherapy drug and it was first used to treat acute leukemia. To this day, we still question if — or how — it could affect fertility or a developing fetus. Women with sickle cell disease are at risk for diminished ovarian reserve, but there has been a question about whether it is due to hydroxyurea or the disease itself, which causes end-organ damage. Those effects likely extend to the uterus and ovarian tissue.
I am relieved to see the findings of this real-world study. Women who were on hydroxyurea during the first trimester generally had good outcomes and no specific issues that could be contributed to hydroxyurea were seen in the newborns.
I have several patients with sickle cell disease who are pregnant who stopped using hydroxyurea before they tried to conceive, and they are having more complications. They are on exchange transfusions and they have developed new antibodies. Other patients are at the point where they need to make a decision about whether to stop hydroxyurea before they try to get pregnant. They know how much the medication has helped reduce complications, and they are very worried about what might happen if they stop.
There is a reason this abstract was selected for plenary session presentation. These data are incredibly important. We cannot go as far as to say hydroxyurea is completely safe, but it is always helpful to have real-world data to guide shared decision-making with our patients.
Disclosures: Ali reports no relevant financial disclosures.
Sources/Disclosures
Source:
Habibi A, et al. Abstract 2. Presented at: ASH Annual Meeting and Exposition; Dec. 6-9, 2025; Orlando.
Disclosures:
Habibi reports relationships with Novo Nordisk, Pfizer and Theravia. Please see the study for all other authors’ relevant financial disclosures.
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