Is hydroxyurea safe to take during pregnancy?

Hydroxyurea Should Be Avoided During Pregnancy

Hydroxyurea is teratogenic and should be discontinued before conception, though emerging evidence suggests risks may be lower than previously thought, particularly if exposure is limited to the periconceptional period rather than throughout pregnancy.

Guideline Recommendations

Clear Contraindication

• Hydroxyurea is classified as teratogenic and must be avoided in women contemplating pregnancy 1, 2
• The FDA label explicitly states hydroxyurea can cause fetal harm based on animal studies and mechanism of action, with animal data showing embryotoxicity and malformations at doses 0.3-0.8 times the human dose 2
• NCCN guidelines recommend against hydroxyurea use during pregnancy, especially in the first trimester, if possible 1

Preconception Planning

• Women on hydroxyurea should be switched to interferon-alpha before attempting pregnancy 1
• Pregnancy testing should be verified prior to initiating hydroxyurea therapy 2
• Females must use effective contraception during treatment and for at least 6 months after stopping hydroxyurea 2
• Males with female partners of reproductive potential should use contraception during treatment and for at least 1 year after stopping 2

Disease-Specific Context

Myeloproliferative Neoplasms (ET/PV)

• If cytoreductive therapy is needed during pregnancy, interferons (interferon alfa-2b, peginterferon alfa-2a, peginterferon alfa-2b) are the preferred agents 1
• Patients on hydroxyurea prior to pregnancy should be switched to interferons 1

Chronic Myeloid Leukemia

• The NCCN panel recommends against hydroxyurea use during pregnancy, especially in the first trimester 1
• If treatment is deemed necessary, interferon can induce and maintain hematologic remission 1
• The potential benefit to the mother versus risk to the fetus must be carefully evaluated on an individual basis if considering any cytoreductive therapy 1

Emerging Research Evidence

Recent Systematic Review Findings

• A 2025 systematic review of 567 pregnancies exposed to hydroxyurea found neither teratogenic nor hematologic effects on the fetus were observed 3
• The review concluded that pregnancy risks associated with hydroxyurea are lower than anticipated 3

Timing-Dependent Risk

• A 2022 study of 1788 pregnancies found that hydroxyurea use during conception and pregnancy (but not conception only) was associated with increased odds of miscarriage/stillbirth (OR 2.21,95% CI 1.40-3.47) 4
• This suggests hydroxyurea may be safer if discontinued at conception rather than continued throughout pregnancy 4
• Hydroxyurea use during conception and pregnancy was associated with low birth weight in full-term infants (OR 2.98) but not with prematurity or serious medical problems at birth 4

Historical Case Series

• Multiple case reports from 1999-2009 documented live births without congenital anomalies following hydroxyurea exposure 5, 6
• However, these studies had small sample sizes and insufficient follow-up to establish definitive safety 5

Critical Caveats

Breastfeeding

• Hydroxyurea is excreted in breast milk and breastfeeding must be discontinued during treatment 1, 2

Risk-Benefit in Severe Disease

• The most recent evidence (2025) suggests that use of hydroxyurea in pregnancy may be justified considering the significant risks of untreated conditions like sickle cell disease 3
• However, this conflicts with established guidelines and FDA labeling, which maintain stronger warnings 1, 2

Monitoring Requirements

• If hydroxyurea exposure occurs inadvertently during pregnancy, close monitoring is essential 1
• Animal studies showed growth retardation and impaired learning ability with single high doses 2

Practical Algorithm

1. Before pregnancy: Discontinue hydroxyurea and switch to interferon-alpha if cytoreductive therapy is needed 1
2. If pregnancy discovered while on hydroxyurea: Discontinue immediately and switch to interferon if treatment is necessary 1
3. If continued treatment is absolutely required: Interferon is preferred over hydroxyurea, though the decision must weigh maternal disease severity against fetal risk 1
4. Postpartum: Hydroxyurea can be restarted after delivery, but breastfeeding must be avoided 1, 2

The weight of guideline evidence strongly supports avoiding hydroxyurea during pregnancy, despite emerging research suggesting lower risks than previously thought 1, 2, 3.