What is the recommended management of hydroxyurea (hydroxycarbamide) in pregnant patients with sickle cell disease?

Hydroxyurea Management in Pregnant Patients with Sickle Cell Disease

Hydroxyurea must be discontinued in pregnant women with sickle cell disease due to established teratogenic risk in animal models, despite emerging human data suggesting lower-than-anticipated fetal harm. 1

Preconception Management

Women of childbearing potential taking hydroxyurea should discontinue the medication at least 3 months before attempting conception. 1 This washout period allows for drug clearance and minimizes potential teratogenic exposure during the critical early weeks of pregnancy when organogenesis occurs.

• Effective contraception is mandatory for all women on hydroxyurea therapy 1
• Preconception counseling should address the high-risk nature of pregnancy in sickle cell disease, independent of medication exposure 2

Management Upon Discovery of Pregnancy

If pregnancy occurs while on hydroxyurea, immediately discontinue the medication. 1 The American Society of Hematology guidelines explicitly note that hydroxyurea has been demonstrated to be teratogenic in animal models at high doses 2, and current FDA labeling classifies it as contraindicated in pregnancy 1.

Alternative Disease Management During Pregnancy

Since hydroxyurea cannot be continued, pregnant women with sickle cell disease require alternative strategies:

• On-demand transfusion is the standard approach for most pregnant women with sickle cell disease 2
• Prophylactic scheduled transfusions should be considered for high-risk patients with: 2
  • History of severe SCD-related complications before current pregnancy (recurrent pain crises, acute chest syndrome)
  • Previous pregnancy complications related to sickle cell disease
  • Additional high-risk obstetrical features (nephropathy, other medical comorbidities)
  • Development of SCD-related complications during the current pregnancy

The American Society of Hematology does not recommend routine prophylactic transfusion for all pregnant women with sickle cell disease, given very low certainty evidence 2. However, one randomized trial showed scheduled transfusions reduced maternal pain episodes (OR 0.16,95% CI 0.05-0.51) though not fetal complications 2. Observational data suggested benefits for both maternal outcomes (reduced pain, pulmonary complications, mortality) and fetal outcomes (reduced preterm birth and mortality) 2.

Emerging Evidence and Clinical Nuance

Recent human data challenges the absolute contraindication but does not yet justify routine use. A 2025 systematic review of 567 pregnancies exposed to hydroxyurea found no teratogenic or hematologic effects on fetuses 3. However, a 2022 observational study from the Sickle Cell Disease Implementation Consortium (1788 pregnancies) found that hydroxyurea use during conception and pregnancy (not conception alone) was associated with increased miscarriage/stillbirth risk (OR 2.21,95% CI 1.40-3.47) and low birth weight in full-term infants (OR 2.98,95% CI 1.09-7.38) 4.

Critical Interpretation of Conflicting Data

• The 2022 study suggests hydroxyurea may be safe up to the time of conception but should be discontinued once pregnancy is confirmed 4
• The discrepancy between studies may reflect differences in disease severity, timing of exposure, and confounding by indication (sicker patients more likely to continue hydroxyurea) 5
• Current guidelines maintain the contraindication despite emerging data 1

Lactation Considerations

Breastfeeding must be discontinued during hydroxyurea treatment because the drug is excreted in breast milk. 1 Women who require hydroxyurea postpartum should not breastfeed.

Common Pitfalls to Avoid

• Failing to provide preconception counseling to all women of childbearing age on hydroxyurea, missing the opportunity for planned discontinuation 1
• Continuing hydroxyurea throughout pregnancy based on emerging safety data without recognizing that current guidelines still contraindicate use 1
• Inadequate monitoring of pregnant women after hydroxyurea discontinuation, leading to preventable sickle cell complications that could harm both mother and fetus 2
• Not considering prophylactic transfusion in truly high-risk patients (history of severe complications, current pregnancy complications), where benefits may outweigh transfusion risks 2

Monitoring During Pregnancy After Hydroxyurea Discontinuation

Pregnant women with sickle cell disease require intensive surveillance regardless of prior hydroxyurea use:

• Monthly clinical assessment for pain crises, acute chest syndrome, and other SCD complications 2
• Serial ultrasound with Doppler assessment starting at 20-24 weeks to monitor for intrauterine growth restriction and placental insufficiency 2
• Hemoglobin monitoring to guide transfusion decisions (target >7.0 g/dL if transfusing) 2