Sickle cell disease (SCD) has many systemic complications including vaso-occlusive crises (VOC), stroke and increased mortality. However, as a result of advances in the care of children with SCD, over 90% of those born with SCD in the US live until they are at least 20 years of age. As survival improves, more women with SCD are able to have children. Through improvements in the management of pregnancy, the majority of women with SCD can have an uncomplicated birth though they do have a high incidence of medical and pregnancy complications compared to those women with normal phenotype. While current literature regarding pregnancy in SCD often compares sickle cell patients to normal hemoglobin phenotype patients, more research is needed comparing individuals with SCD. This study seeks to examine the number of vaso-occlusive crises, acute chest syndrome (ACS) episodes and thromboembolic events in pregnant patients with SCD, comparing during pregnancy, the 12 months before and the 12 months after pregnancy.
A 10-year retrospective study was conducted at University of Illinois Health System (UIH) and included women over the age of 18 with sickle cell disease and pregnancy. These patients followed primarily at UIH for both their sickle cell and obstetric care. The query included 208 pregnancies and 177 patients. The primary endpoint was to compare the number of VOC, ACS, and thromboembolic events in patients with sickle cell disease during 9 months of pregnancy, the 12 months prior to their pregnancy and the 12 months after their pregnancy. Secondary endpoints include prophylactic, simple, and exchange transfusions throughout the pregnancy, mode of delivery, obstetric complications (preeclampsia, eclampsia, mortality), and fetal complications (IUGR, Apgar scores, mortality).
Of 208 pregnancies from the initial query, 121 met inclusion criteria for the study. 87 of the 208 pregnancies met exclusion criteria due to other hemoglobin genotypes, delivery outside the study timeframe, delivery at outside hospital, or encounters for ectopic pregnancies, spontaneous or elective abortions. Paired comparisons between pregnancy, 12 months before the pregnancy, and 12 months after the pregnancy were carried out using non-parametric method (Wilcoxon's test) or generalized mixed effects models. Results demonstrated a statistically significant increase in VOC and ACS during pregnancy, compared to the 12 months prior and 12 months after pregnancy, as demonstrated in Table 2. Thromboembolic events had a slight trend of increase during pregnancy compared to the period before or after. These results were adjusted for age at delivery and restricted to SS genotype. VOC and severe genotype were found to associate with maternal and fetal outcomes such as C-section (p=0.04), transfusion requirement at delivery (p=0.007), low birth weight (p=0.008), and preterm delivery (p=0.02).
Our findings demonstrate a definitive and statistically significant increase in VOC and ACS during pregnancy compared to the 12 months before or after pregnancy among women with SCD. This unique study compares patients with SCD to themselves longitudinally through time, utilizing a superior control group. Although this increase in VOC and ACS has been observed previously, prior studies compared pregnant patients with SCD to other patients with SCD, or to controls with normal hemoglobin. As hypothesized, thromboembolic events had a slight trend towards increasing during pregnancy, however this comparison was not statistically significant. Although prior data has shown prophylactic transfusions to decrease VOC in pregnant women with SCD, prophylactic transfusions were rarely utilized in this study group. These results demonstrate a definitive increase in VOC in pregnant individuals with SCD, and additionally affecting maternal and neonatal outcomes. Based on this study, decreasing rates of VOC during pregnancy may improve maternal and fetal outcomes. This may be achieved with prophylactic transfusions; however additional studies must be conducted to improve care in this patient population. This study will also allow us to further investigate additional characteristics that change during this timeline during pregnancy. This offers new opportunities to institute individualized preventive strategies, expanding the role of personalized medicine in the care of sickle cell patients.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.