Background and Significance: Sickle cell disease (SCD) affects pregnancy outcomes with high maternal and fetal morbidity rates. Over 50% of pregnant women with SCD experience vaso-occlusive crises (VOC), with acute chest syndrome occurring in 7-20% of hemoglobin (Hb) SS pregnancies. Other complications include high rates of preeclampsia, venous thromboembolism, intrauterine growth restriction, preterm delivery, and small-for-gestational-age infants. Some of these complications could be attributed to sickle cells resulting in impaired uteroplacental blood flow and oxygen delivery. While prophylactic red blood cell (RBC) transfusion has established benefits for stroke prevention and preoperative optimization in SCD, its role in pregnancy remains poorly defined. With hydroxyurea (HU) contraindicated due to its teratogenicity, RBC transfusion represents the only available disease-modifying therapy for pregnant women with SCD. Despite widespread clinical use, no consensus exists among providers regarding chronic RBC transfusion for preventing SCD-related pregnancy complications and the current standard of care (SOC) employs HU discontinuation and on-demand RBC transfusion during acute SCD VOC events.

Study Objectives: The primary objective is to determine if prophylactic RBC transfusion reduces episodes of acute SCD manifestations or pregnancy-related complications requiring acute healthcare encounters or resulting in death during pregnancy until 8 weeks postpartum in women with SCD when compared to SOC. Secondary objectives include evaluating effects on fetal outcomes and assessing transfusion-related complications including alloimmunization and iron overload.

Study Design and Methods This is a prospective, randomized, controlled, parallel two-arm pilot study comparing prophylactic RBC transfusion versus SOC in pregnant women with SCD.

Study Population: Includes pregnant adult patients with SCD at 6-20 weeks gestation. This single-center study is conducted at the Georgia Comprehensive Sickle Cell Center at Grady Memorial Hospital in Atlanta.

Major inclusion criteria: Female gender, electrophoresis confirmed SCD diagnosis of any genotype (HbSS, HbSC, HbSβ thalassemia), age ≥18 years, current pregnancy between 6-20 weeks gestation and ability to provide informed consent.

Major exclusion criteria: Current chronic RBC transfusion therapy prior to pregnancy, prior history of delayed hemolytic transfusion reaction with hyperhemolysis, RBC antibody history preventing adequate transfusion support, inability to receive blood transfusion for social/religious/clinical reasons, and major medical/psychiatric comorbidities precluding trial participation.

Intervention: Study treatment consists of participants randomized to the intervention arm receiving leukoreduced, ABO, Rh (D/Cc/Ee) and Kell-matched RBC transfusions at 3–6-week intervals targeting pre-transfusion HbS <30% from enrollment through 8 weeks postpartum. Patients with baseline Hb <10 will undergo simple transfusion while those with baseline Hb ≥10 will undergo RBC exchange transfusion. Control group will receive SOC with on-demand RBC transfusions as clinically indicated. Both groups receive management of acute SCD manifestations per The National Heart, Lung, and Blood Institute/American Society of Hematology guidelines.

Primary endpoint: This includes composite number of episodes of acute SCD manifestations or pregnancy-related complications requiring acute healthcare encounters (emergency department/acute care/hospital visits) or resulting in death from enrollment through 8 weeks postpartum.

Secondary endpoints: This includes fetal outcomes (birthweight, gestational age, neonatal intensive care admission, fetal demise/stillbirth), patient-reported outcomes using modified ASCQ-Me and PROMIS instruments, and placental pathology analysis in both study arms to determine effects of transfusion on maternal-fetal perfusion.

Safety endpoints: This includes development of new RBC alloantibodies, transfusion reactions, and transfusion related iron overload.

Recruitment goal and analysis: The study wide goal is to recruit 50 patients and randomized them in a 1:1 ratio to the intervention or SOC arm. Analysis will be done using relative risk reduction with 95% confidence interval and at a 5% significance level.

Current Status: This study has received IRB approval, is currently open and actively enrolling participants.

ClinicalTrials.gov identifier: NCT06979492

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2025
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