Severe maternal morbidity according to sickle cell disease genotype

Abstract Background Sickle cell disease (SCD) is a genetic hemoglobinopathy that disproportionately affects individuals of African descent and is associated with elevated risks of maternal complications. However, the contribution of specific SCD genotypes to severe maternal morbidity (SMM) and postpartum readmission remains poorly characterized at the population level. Objective We sought to examine the association between SCD genotypes—hemoglobin SS (HbSS) disease, hemoglobin SC (HbSC) disease, sickle thalassemia, and sickle cell trait—and SMM, hospital readmission, and related adverse maternal outcomes. Study design This was a retrospective cohort study using the Nationwide Readmissions Database from 2016 through 2022, representing over 20 million weighted delivery hospitalizations. SCD genotypes were identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes. The primary outcome was SMM (non‐transfusion, no sickle crisis), identified using the Centers for Disease Control and Prevention algorithm, excluding transfusion and sickle cell crisis. Secondary outcomes included transfusion, hospital readmission within 42 days, and sickle cell crisis. Adjusted relative risks (aRRs) with 95% confidence intervals (CIs) were estimated using survey‐weighted modified Poisson regression, adjusting for demographic, clinical, and hospital‐level characteristics. Results Among 20,928,182 delivery hospitalizations, 13,501 had HbSS disease, 1526 had HbSC disease, 2063 had sickle thalassemia, 149,219 had sickle cell trait, and 20,761,873 had no SCD or trait. Compared with individuals without SCD or trait, SMM risk was substantially elevated among those with HbSS disease (6.0%; aRR, 5.81; 95% CI, 5.25–6.43), HbSC disease (7.9%; aRR, 6.06; 95% CI, 4.66–7.87), sickle thalassemia (3.5%; aRR, 3.61; 95% CI, 2.57–5.06), and sickle cell trait (1.4%; aRR, 1.41, 95% CI, 1.32–1.50). A similar graded pattern was observed for hospital readmission and transfusion. When compared with HbSS disease directly, no statistically significant difference in SMM risk was detected for HbSC disease (aRR, 1.21; 95% CI, 0.92–1.59), whereas sickle thalassemia was associated with a lower risk (aRR, 0.63; 95% CI, 0.44–0.89). Conclusion SCD is associated with markedly elevated risks of SMM, transfusion, and hospital readmission, with the magnitude varying by genotype. HbSS and HbSC disease confer markedly elevated risks, with no statistically significant difference detected between the two genotypes. Sickle thalassemia is associated with comparatively lower but still clinically significant risks. These findings underscore the need for genotype‐informed, multidisciplinary peripartum management.