Trajectory of Blood Pressure in Pregnant People with Sickle Cell Disease: A Multinational Study

INTRODUCTION Pregnancy in people with sickle cell disease (SCD) is high-risk for adverse outcomes including hypertensive disorders of pregnancy (HDP). HDP can result in acute and chronic morbidity for the pregnant person and fetus. However normal parameters for blood pressure (BP) in SCD pregnancies are not established. BP may be different during pregnancy for people with SCD, especially with sickle cell anemia, who have lower BP at baseline than the general population. Whether normal BP during SCD pregnancy differs from normal values in unaffected pregnancies is unknown.

In the general population, BP decreases during pregnancy, nadirs at 22-24 weeks, and returns to baseline peripartum. Defining normal BP values in pregnant people with SCD is necessary to better define physiologic pregnancy adaptations in SCD and to inform monitoring and treatment decisions, for which little data currently exists. This study describes the trajectory of BP across pregnancy in people with SCD and compares BPs by clinical variables including genotype and the use of chronic transfusion therapy.

METHODS We reviewed the medical records of people with SCD who delivered singleton pregnancies of at least 20 weeks’ gestation at Mount Sinai Hospital, Toronto (1990-2017) or Johns Hopkins Hospital (2000-2021). We collected laboratory values, SCD complications, comorbidities, medication exposures, transfusion practices, labor and delivery information, and fetal outcomes. We documented the highest systolic and diastolic blood pressure (SBP and DBP) captured in seven time periods: before pregnancy, at initial prenatal visit, 20-28 weeks’ gestation, 28-34 weeks’ gestation, last outpatient visit before delivery, admission for birth, and six weeks postpartum.

We compared demographic and clinical features in people with hemoglobin-SS or hemoglobin-Sβ⁰ thalassemia (HbSS/HbSβ⁰) to those with hemoglobin-SC or hemoglobin-Sβ⁺ thalassemia (HbSC/HbSβ⁺). Appropriate hypothesis tests were applied. We assessed BP trajectories throughout the pregnancy, among the entire sample and by clinically relevant subgroups.

RESULTS The sample included 292 singleton pregnancies among 198 patients (Table). People with HbSC/HbSβ⁺ comprise about 30% of the SCD population at each center and 42% of the pregnancies in this study.

In unstratified analysis, BP trajectories matched the pattern typically seen in healthy pregnant people: SBP nadired at 20-28 weeks’ gestation, peaked during labor, and returned to baseline by six weeks postpartum.

BP trajectories differed by genotype group (Figure). The HbSS/HbSβ⁰ patients had lower baseline SBP and DBP than the HbSC/HbSβ⁺ group. In people with HbSS/HbSβ⁰, BP nadir occurred at 12 weeks’ gestation, while the HbSC/HbSβ⁺ group's BP nadir was at 20-28 weeks’ gestation. The BP values of the groups converged during the third trimester and at admission for birth. Both groups returned to baseline postpartum. BP did not differ based on the use of chronic transfusions.

Here, 16% (n=46) of pregnancies were diagnosed with gestational hypertension [HbSS/HbSβ⁰: 15% (n=25); HbSC/HbSβ⁺: 17% (n=21); p=.75], 12% (n=35) with preeclampsia [HbSS/HbSβ⁰: 14% (n=24); HbSC/HbSβ⁺: 9% (n=11); p=.20], and one, a HbSS patient, with eclampsia. In 5% (n=16) of pregnancies, patients had severe range hypertension [HbSS/HbSβ⁰: 4% (n=6), HbSC/HbSβ⁺: 8% (n=10), p=.12]. Thirty-three patients received aspirin for preeclampsia prevention after the release of guidelines supporting its use [HbSS/HbSβ⁰: 44% (n=21); HbSC/HbSβ⁺: 38% (n=12); p=.58]. Sixteen patients received magnesium sulphate for eclampsia prevention [HbSS/HbSβ⁰: 5% (n=8); HbSC/HbSβ⁺: 6% (n=8); p=.41].

CONCLUSIONS In this large, multinational cohort of SCD pregnancies, the risk of HDP based on existing definitions was similar in HbSS/HbSβ⁰ and HbSC/HbSβ⁺ groups. As expected, those with HbSS/HbSβ⁰ had lower baseline BP than those with HbSC/HbSβ⁺. The BP nadir occurred earlier in pregnancy for HbSS/HbSβ⁰, suggesting that HbSS/HbSβ⁰ patients do not undergo the same cardiovascular adaptations as the general population, possibly due to reduced cardiovascular reserve. BP trajectory in the HbSC/HbSβ⁺ was similar to the non-SCD pregnant population. Our data demonstrate lower baseline BP in pregnant people with HbSS/HbSβ⁰, supporting close monitoring for even a modest upward trend in BP and re-examination of the appropriate BP thresholds to define HDPs in SCD.

Malinowski:Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy. Kuo:Alexion: Consultancy, Honoraria; Apellis: Consultancy; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Consultancy; bluebird bio: Consultancy; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Honoraria; Bioverativ/Sanofi/Sangamo: Membership on an entity's Board of Directors or advisory committees. Pecker:GBT: Research Funding; Novo Nordisk: Consultancy; Global Blood Therapeutics: Consultancy.