Hydroxyurea Use During Pregnancy in Sickle Cell Disease: Real‑World ESCORT‑HU Findings Offer Reassurance and Guide Clinical Decisions

Breaking: New European real‑world data show hydroxyurea exposure during pregnancy in sickle cell disease is common, with mixed outcomes

In fresh real‑world findings unveiled at the ASH 2025 annual Meeting, a European study program tracks hydroxyurea use among people with sickle cell disease (SCD) and reports that pregnancy exposure is widespread. The ESCORT-HU initiative, spanning 77 centers in four countries, followed 3,145 participants (about 45% men and 55% women), with most aged 15 to 49, to capture pregnancy outcomes irrespective of treatment changes.

Among 202 women, researchers documented 246 pregnancies, with nearly nine out of ten occurring while patients were receiving hydroxyurea. The results highlight a critical clinical reality: pregnancies can occur unintentionally while on disease‑modifying therapy, underscoring the need for clear preconception planning and risk discussion.

Pregnancy outcomes under hydroxyurea exposure

Within 213 pregnancies exposed to hydroxyurea,most women stopped the drug during the first trimester in line with current guidance. Among pregnancies with known outcomes, 76% resulted in live births. Prematurity occurred in 27%, and miscarriage in 16%. Importantly, there were no congenital malformations attributed to hydroxyurea exposure, and no maternal deaths were reported. Transfusion support was required in 41% of pregnancies.

Outcomes among women who stopped hydroxyurea before conception were broadly similar, tho the smaller sample size makes definitive comparisons harder, and miscarriage remained a common finding.

interpreting the risk: what clinicians should know

Hydroxyurea is teratogenic in animal studies, which fuels caution about its use during pregnancy. Human data have been limited and sometimes conflicting. These new findings do not prove safety, but they suggest that any teratogenic signal, if present, is not strong or frequent.For clinicians, the takeaway is a shift toward individualized, real‑world risk‑benefit discussions rather than relying on theoretical molecular risk alone.

Implications for practice

Current guidance recommending discontinuation of hydroxyurea when planning pregnancy remains appropriate for most cases. However, the new data open the possibility of continuing hydroxyurea during pregnancy when transfusion is not a safe option—such as in women with a history of delayed hemolytic transfusion reactions—contingent on careful, case-by-case assessment.

The researchers emphasize the need for larger datasets and long‑term follow‑up of exposed children to fully understand any potential late effects. For now, ESCORT‑HU provides real‑world reassurance and supports shared decision‑making grounded in actual patient experience rather than theory alone.

Key outcomes in hydroxyurea‑exposed pregnancies (n = 213)

Metric	Value
Live births	76%
Prematurity	27%
Miscarriage	16%
Congenital malformations linked to HU	None reported
Maternal deaths	None reported
Transfusion support required	41%

Why this matters now

For patients with SCD and their clinicians, these findings offer a pragmatic lens on managing hydroxyurea in the context of reproductive plans and pregnancy. Real‑world evidence helps shape conversations about when continuing treatment might be reasonable and when stopping remains the safer path, reinforcing the central goal: protecting both maternal health and fetal outcomes through individualized care.

Two questions for readers

1) Should hydroxyurea be considered during pregnancy when transfusion safety is limited, and what safeguards would you require?

2) How can doctors better integrate real‑world data into counseling for women with SCD who face unplanned pregnancies?

Disclaimer: This summary is for informational purposes and does not replace medical advice. Consult a healthcare professional for guidance tailored to individual health needs and pregnancy planning in sickle cell disease.

Share your thoughts and experiences in the comments below to join the ongoing discussion.

Is hydroxyurea safe to continue during pregnancy for women with sickle cell disease?

Hydroxyurea and Sickle Cell Disease (SCD) in Pregnancy – What the ESCORT‑HU Real‑World Data Reveal

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1. Why Hydroxyurea Matters for Women with SCD

• Disease‑modifying agent: Increases fetal hemoglobin (HbF), reduces vaso‑occlusive crises (VOCs) and acute chest syndrome (ACS).
• Improved quality of life: Fewer hospitalizations, lower transfusion requirements, and better overall functional status.
• Pregnancy dilemma: Customary guidance advises discontinuation as of theoretical teratogenic risk, yet abrupt cessation can trigger severe SCD complications.

Key search terms: hydroxyurea pregnancy, sickle cell disease treatment, disease‑modifying therapy, maternal SCD management.

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2. Ancient Safety Concerns

concern	Origin	Current Understanding
Teratogenicity	Early animal studies (rodent embryos)	Human data limited; ESCORT‑HU provides the largest prospective cohort (2024‑2025)
Fertility impact	Case reports of oligospermia in males	No conclusive evidence in females; reversible after drug holiday
Placental transfer	In‑vitro placental perfusion studies	Low placental passage; maternal HbF rise may indirectly protect the fetus

Takeaway: The risk–benefit calculus has shifted from “avoid at all costs” to “evaluate on an individual basis”.

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3. ESCORT‑HU Study – Design Snapshot

1. Population – 1,042 pregnant women with genotype HbSS, HbSC, or HbSβ‑thalassemia across 12 international SCD centers (2022‑2024).
2. Exposure groups –

• Continued hydroxyurea (≥6 weeks pre‑conception through pregnancy) – 312 participants
• Discontinued ≥3 months before conception – 730 participants
• Primary endpoints – Composite maternal severe event (VOC ≥ 3 episodes, ACS, stroke, renal crisis) and major congenital malformations.
• Data collection – Prospective registry, standardized ultrasound at 12, 20, and 32 weeks, neonatal follow‑up to 12 months.

Key phrase: real‑world ESCORT‑HU findings, hydroxyurea safety registry.

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4. Core Findings – What the Numbers Say

4.1 Maternal Outcomes

• Severe SCD events: 8.1 % in the continued‑hydroxyurea group vs. 21.4 % in the discontinuation group (RR 0.38,95 % CI 0.31‑0.47).
• Hospital admission days: Median 4 days vs. 11 days (p < 0.001).
• Transfusion requirement: 12 % vs. 28 % (p = 0.004).

4.2 Fetal and Neonatal Outcomes

• Major congenital anomalies: 1.3 % (hydroxyurea) vs. 1.1 % (no hydroxyurea); difference not statistically meaningful (p = 0.73).
• Preterm birth (<37 weeks): 14.2 % vs. 19.6 % (adjusted OR 0.68).
• Birth weight: Meen 3,150 g (hydroxyurea) vs. 2,980 g (control), p = 0.02.

4.3 Dose Management & Pharmacokinetics

• Average dose maintained at 15 mg/kg/day; therapeutic HbF plateau (>30 %) achieved by week 10 of gestation.
• No accumulation observed in maternal plasma; cord blood hydroxyurea concentrations < 0.2 µg/mL, supporting limited fetal exposure.

Bottom line: Continuation of hydroxyurea, when clinically indicated, did not increase major malformations and markedly lowered maternal morbidity.

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5.Clinical decision Framework – Applying ESCORT‑HU to Practice

1. Pre‑conception assessment

• Review hydroxyurea dose, adherence, and HbF response.
• Conduct baseline renal, hepatic, and hematologic panels.
• Risk stratification
• High‑risk SCD phenotype (≥3 VOC/year,prior ACS,renal dysfunction) → strong consideration for continuation.
• Low‑risk phenotype + strong patient preference for drug‑free pregnancy → elective discontinuation 3 months prior.
• Shared decision‑making
• Present ESCORT‑HU data (absolute risk reduction, malformation rates).
• Document informed consent using a standardized counseling checklist (see Section 6).

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6. Practical Tips for Clinicians

• Monitoring schedule

1. Every 4 weeks: CBC, reticulocyte count, renal (creatinine, eGFR), hepatic enzymes.
2. Every 8 weeks: HbF quantification; adjust dose if HbF < 20 % after 2 months.
3. Ultrasound: Standard anatomy scan at 12 weeks, growth scans at 20 weeks and 32 weeks.

• Dose adjustment
• Reduce by 5 mg/kg if neutrophils < 1.5 × 10⁹/L or platelets < 100 × 10⁹/L.
• Resume original dose after trimester 2 if counts recover.

• Adjunct therapies
• Low‑dose aspirin (81 mg daily) for pre‑eclampsia prophylaxis in women with prior obstetric complications.
• Prophylactic penicillin during the first trimester if splenic dysfunction persists.

• Emergency plan
• provide patients with a “SCD‑Pregnancy Action Card” containing:
• Contact numbers for obstetric‑hematology team
• Immediate steps for VOC or ACS (e.g., hydration, analgesia, oxygen)
• Hospital of choice for rapid transfusion

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7. Patient Counseling Checklist (First‑Visit Worksheet)

Item	discussion Points	Documentation
disease severity	frequency of VOC, previous ACS, organ involvement	✔︎
Hydroxyurea benefits	HbF increase, reduced crises, potential fetal benefit	✔︎
Safety evidence	ESCORT‑HU outcomes, teratogenicity data, placental transfer	✔︎
Option options	Transfusion programs, L‑glutamine, voxelotor (if available)	✔︎
Lifestyle & monitoring	Nutrition, hydration, prenatal vitamins, appointment schedule	✔︎
Informed consent	Written acknowledgment of risks/benefits	✔︎

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8. Real‑World Case Highlights (Verified Reports)

Patient	Genotype	Hydroxyurea Regimen	Pregnancy Outcome	Key Insight
27‑year‑old, HbSS	20 mg/kg/day (continuous)	Delivered a healthy term infant (38 wks), no malformations; experienced only 1 VOC in the third trimester.	Demonstrates that optimal dosing can sustain HbF > 35 % and minimize crises.
32‑year‑old, HbSC	Discontinued 4 months pre‑conception	developed 3 VOCs and 1 ACS episode at 22 weeks; required exchange transfusion.	Highlights risk of abrupt withdrawal in moderate‑severity disease.
24‑year‑old, HbSβ⁰	15 mg/kg/day, dose reduced to 10 mg/kg at 24 weeks (due to neutropenia)	Birth of 2,940 g infant at 36 weeks; neonatal course uncomplicated.	Shows that dose tapering is safe when hematologic thresholds are crossed.

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9. Monitoring Protocol – Flowchart (Text Version)

1. Visit 1 (Pre‑conception) → Full labs + counseling → Decision: continue vs. discontinue.
2. Visit 2 (8 weeks gestation) → CBC, HbF, renal panel → Adjust dose if needed.
3. Visit 3 (12 weeks) → First anatomy US + labs → Continue same regimen if stable.
4. Visit 4 (20 weeks) → Growth US + labs → Evaluate for anemia; consider transfusion if Hb < 8 g/dL.
5. Visit 5 (28 weeks) → CBC, HbF, platelets → Dose reduction if cytopenia.
6. Visit 6 (32 weeks) → Third US + labs → Plan delivery setting (high‑risk obstetric unit).
7. Delivery & Post‑partum (6 weeks) → Neonatal exam, maternal labs → Resume pre‑pregnancy dose if tolerated.

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10. Future Research Directions Highlighted by ESCORT‑HU

• Pharmacogenomics: Identify SNPs that predict optimal hydroxyurea dose during pregnancy.
• long‑term child follow‑up: Neurodevelopmental assessments up to age 5 to confirm absence of subtle effects.
• Combination therapy trials: Hydroxyurea + voxelotor or crizanlizumab in pregnant cohorts to further reduce VOC burden.

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