Pregnancy related complications and placenta pathology in pregnant women with sickle cell disease

Abstract Background: Among pregnant women with sickle cell disease (SCD), studies have shown an increased risk of complications such as maternal pain crises, pre-eclampsia, and thromboembolic events, and fetal intrauterine growth restriction (IUGR), preterm and low birth weight, compared to the general population. Despite advancements in care to improve survival rates for individuals with SCD, studies regarding these complications are limited and pregnancy in SCD remains without robust guidelines on optimal clinical management. This study examines post-partum complications, including placental pathology, in women with SCD and explores associated SCD-related risk factors. Methods: This was a single center retrospective study of pregnant women with SCD at the Georgia Comprehensive Sickle Cell center at Grady Health System, Atlanta, Georgia between 2020-2025. Descriptive analyses of baseline demographic and clinical characteristics such as SCD genotype, hemoglobin (Hb) levels, and ongoing SCD therapy, were examined pre-pregnancy and during pregnancy. Post-partum maternal and fetal complications, healthcare utilization, as well as available placental morphology were assessed. Appropriate chi-square and T-tests were utilized with significance level p = 0.05. This study was conducted with IRB approval. Results: Sixty-eight SCD pregnant women were included, age ranged from 18-42 (mean-27.7; SD- 5.0) years. The most common genotypes were Hb SS (n=36; 53%), and Hb SC (n=21; 31%), others seen were Hb SB0, Hb SB+ and Hb SF (n=11). Mean baseline hemoglobin before pregnancy ranged from 6.5-13 (mean- 9.1g/dL; SD- 1.64) and mean fetal hemoglobin before pregnancy was 9.1% (SD 7.1). During pregnancy, the mean maternal hemoglobin ranged from 6.1-11 (mean- 8.7 g/dL; SD- 1.19). Reduced hemoglobin (8 g/dL) during pregnancy was seen in 19 patients (vs. 49 patients with ≥8 g/dL) and was associated with higher preeclampsia (47% vs. 16%; p-value 0.0133), and fetal IUGR (47% vs. 14%; p-value 0.0074); with no difference in the frequency of vaso-occlusive crises (VOC), or presence of placental abnormalities. Twenty-five patients (36.7%) overall were on hydroxyurea before pregnancy and only two (2.9%) on chronic exchange. Amongst patients on hydroxyurea pre-pregnancy (vs. 41 with no disease-modifying therapy), there was no statistical difference in occurrence of VOC, preeclampsia, fetal IUGR, or identified placental abnormalities post-partum. Of the 48 placentas examined, abnormalities with maternal vascular malperfusion were present in 38 samples, mostly seen in the Hb SS population and in cases of preeclampsia/eclampsia. Placenta pathologies most reported included small for gestation placenta, decidual vasculopathy, increased syncytial knot, fibrin deposition, villous dysmaturity, thrombosis and infarct. Conclusion: Study results showed that low hemoglobin levels during pregnancy in SCD patients was associated with higher incident preeclampsia, and fetal IUGR. While more study patients were not on long-term SCD treatment (hydroxyurea or chronic exchange) before pregnancy, hydroxyurea therapy pre-pregnancy was not significantly associated with assessed maternal or fetal complications or placental abnormalities. In addition, more than one in five pregnant SCD patients showed a type of placental abnormality indicative of vascular malperfusion, including small for gestation placentas. These findings suggest that in patients with SCD, it is important to support adequate hemoglobin levels during pregnancy to avoid maternal and fetal complications and improve patient outcomes overall.