Hydroxyurea Exposure Limiting Pregnancy and Follow-Up Lactation (HELPFUL)

The purpose of this research study is to document and understand the effects of hydroxyurea exposure for women with SCD and their babies, during both gestation and lactation.

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease; Sickle Cell Anemia
• Intervention / Treatment: Other: Chart Review; Other: Survey

Detailed Description

Hydroxyurea (hydroxycarbamide) is the primary disease-modifying therapy for individuals with sickle cell disease (SCD) and is both US FDA- and EMA-approved for SCD treatment. Decades of research have documented that hydroxyurea reduces morbidity and mortality for affected patients. Although its primary mechanism of action for SCD is the induction of fetal hemoglobin (HbF) that prevents erythrocyte sickling, hydroxyurea is also a ribonucleotide reductase inhibitor with dose-dependent cytotoxic effects. Based on laboratory data, hydroxyurea is considered to be a potential human mutagen, clastogen, teratogen, and even carcinogen. However, most of these are theoretical human risks; for example, teratogenic effects of hydroxyurea are based on in vitro cellular data and supra-pharmacological dosing of animals, with no documented abnormalities in humans. Despite the lack of in vivo human data, the package insert for hydroxyurea, sold as either Hydrea® or Droxia® (Bristol-Myers Squibb), or as Siklos® (Addmedica) lists both pregnancy and lactation as contraindications for treatment.

This contraindication label is critically important, since women with SCD frequently have high-risk pregnancies throughout gestation, with increased morbidity and mortality for both the mother and baby. Acute clinical complications for the mother occur commonly during gestation, while placental insufficiency through repeated infarctions also leads to increased fetal morbidity. Protection of the mother's health during pregnancy is therefore a high priority, which historically has been aided by judicious use of transfusions and management by a multidisciplinary healthcare team. In the current era, many women with SCD of child-bearing age are taking daily oral hydroxyurea with an excellent treatment effect, so its forced discontinuation around the time of pregnancy represents cessation of effective therapy. Abrupt withdrawal of hydroxyurea is typically deleterious and may not be justified in this setting. Numerous published case reports and small series have described the safe use of hydroxyurea as anti-neoplastic therapy during pregnancy in women with cancer; moreover, anecdotal experience of >100 pregnancies with hydroxyurea exposure did not document any teratogenicity.

Based on the importance of determining the actual risks and benefits of continuing hydroxyurea as disease-modifying therapy during pregnancy to protect both mothers and babies, and the lack of documented in vivo data, the safety of hydroxyurea during gestation and subsequent lactation was recently identified as an important knowledge gap by the NHLBI evidence-based SCD guidelines. Further data collection is needed regarding the actual effects of hydroxyurea for women with SCD during both pregnancy and while breastfeeding. Accordingly, we will conduct a multinational research project to retrospectively capture known human exposures to hydroxyurea in the setting of SCD, which have occurred during gestation and/or lactation, to elucidate the outcomes for the mothers and their babies. Those outcomes will be compared to pregnancies in these same women without hydroxyurea exposure.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Teresa Latham; Phone Number: 513-803-7922; Email: Teresa.Latham@cchmc.org

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
      • Contact: Teresa Latham; Phone Number: 513-803-7922; Email: Teresa.Latham@cchmc.org
      • Contact: Rebecca Geer; Email: Rebecca.Geer@cchmc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Clinical and laboratory data on up to 200 women with SCD with hydroxyurea exposure during either gestation or lactation.

Description

Inclusion Criteria:

• Medical records or data available from previous clinical care prior to June 20, 2019 of pregnant females with SCD, including women who miscarried, had a still birth, or completed labor at any gestational stage, with any hydroxyurea exposure during either pregnancy and/or while breastfeeding.
• Medical records or data available from previous clinical care prior to June 20, 2019 about pregnancy and breastfeeding outcomes, both for babies with hydroxyurea exposure and other babies by these same women.

Exclusion Criteria:

• Unavailable medical records or lack of information about hydroxyurea exposure.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Retrospective Chart Review; Medical record chart review of women seen previously for clinical care prior to June 20, 2019 at participating institutions with SCD and hydroxyurea exposure during gestation or lactation will be identified by healthcare providers.	Other: Chart Review; Medical records or data available from previous clinical care prior to June 20, 2019 about pregnancy and breastfeeding outcomes, both for babies with hydroxyurea exposure and other babies by these same women.
Participant Survey and Retrospective Chart Review; Participants providing their medical records without the assistance of a health care provider will be asked to complete a questionnaire through REDCap and will have the option to upload their deidentified medical records if they are available.	Other: Chart Review; Medical records or data available from previous clinical care prior to June 20, 2019 about pregnancy and breastfeeding outcomes, both for babies with hydroxyurea exposure and other babies by these same women.; Other: Survey; Women who choose to participate directly and provide information in survey format will receive a brief survey and the option to upload their medical records (if available) into Cincinnati Children's maintained REDCap database.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
How long pregnant women with Sickle Cell Disease (SCD) were exposed to Hydroxyurea.	Obtain data on length of time women with SCD were exposed to Hydroxyurea prior to pregnancy, during pregnancy, and after pregnancy.	Through completion of pregnancy, an average of 2 years
Dose of hydroxyurea taken during pregnancy.	Obtain data on the dose of Hydroxyurea taken prior to conception, during and after pregnancy.	Through completion of pregnancy, an average of 2 years
How long infants were exposed to Hydroxyurea.	Obtain data on length of time infants were exposed to Hydroxyurea during gestation and while breastfeeding.	Through study completion, an average of 2 years
Dose of hydroxyurea exposure in infants.	Obtain data on the dose of Hydroxyurea taken by mother during gestation and while breastfeeding infant.	Through study completion, an average of 2 years
Health outcomes of infants exposed to Hydroxyurea.	Obtain data on the health of infant after exposure to Hydroxyurea during gestation and while breastfeeding including any complications of mother's pregnancy or delivery as well as any congenital malformations or medical conditions in infancy.	Through study completion, an average of 2 years
Pregnancy in Sickle Cell Disease (SCD).	Compare pregnancy and delivery complications in women with SCD exposed to Hydroxyurea to pregnancy and delivery complications in women with SCD without Hydroxyurea exposure.	Start of pregnancy until June 2019
Comparative analysis of congenital malformations or medical conditions in infants	Compare the rate of congenital malformations and/or medical conditions in infants exposed to hydroxyurea during gestation and breastfeeding to the rate of these events in infants without hydroxyurea exposure, with data collected descriptively by self-report or chart review as applicable.	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: University of Colorado, Denver; Children's Hospital of Philadelphia; Duke University; Guy's and St Thomas' NHS Foundation Trust; University of Connecticut
• Investigators: Principal Investigator: Russell Ware, MD, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2019
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: August 22, 2019
• First Submitted That Met QC Criteria: September 16, 2019
• First Posted (Actual): September 18, 2019

Study Record Updates

• Last Update Posted (Actual): July 17, 2025
• Last Update Submitted That Met QC Criteria: July 16, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Hydroxyurea
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: HELPFUL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No