Maternal Outcomes in Pregnant Women Admitted with Sickle Cell Disease: A Retrospective Study Involving the National Inpatient Sample (NIS 2016-2021) Database

Background: During the past five decades, there have been significant improvements in supportive care for sickle cell disease (SCD), followed by the development of disease modifying therapies such as hydroxyurea (HU) in the 1990s, and L-glutamine, voxelotor and crizanlizumab more recently. Additionally, there have been exciting developments in potentially curative approaches, such as stem cell transplantation and gene therapy. These developments have resulted in improvement of life expectancy for patients with SCS, from teens in 1970's to late 40's-early fifties in 2000's. Despite these encouraging advances, pregnant women with SCD are reported to have significant morbidity and mortality, compared to the general population, both in low-middle income and high-income settings. Pregnant women with SCD are reported to suffer from a higher rate of hypertensive emergencies such as preeclampsia and eclampsia, as well as intrauterine growth restriction, low birth weight, fetal demise and thromboembolic complications. Methods: To assess the current status of morbidity and mortality associated with pregnancy in women with SCD, we conducted a retrospective analysis using the National Inpatient Sample Database (2016- 2021). Pregnant women with HBSS, HBSC and HBS Beta thalassemia (HBSB) were identified. Chi square analysis was used to determine significance in the demographic datasets. Logistic analysis was used to analyze primary outcome of in-hospital mortality and secondary associated outcomes including, Gestational hypertension, Pre-eclampsia, Eclampsia, Venous Thromboembolism (VTE), Pulmonary Hypertension, Preterm Labour, Intrauterine fetal death (IUFD), Intrauterine growth restriction (IUGR) and mechanical ventilation. Odds ratios were adjusted for age, race and Charlson Comorbidity Index. Results: Observations were weighted to obtain a national estimate of 2.35x 10*7 pregnant women. 25,310 (0.11%) had HBSS, 2465 (0.010%) patients had HBSC disease and 3199 (0.013%) had HB S Beta thalassemia. There was no significant difference in mortality amongst pregnant patients with HBSS, HBSC and HBSB disease. Pregnant patients with SCD had significantly higher odds of being intubated (HBSS - aOR: 2.03, 95% CI:1.22 - 3.37, p-value = 0.006, HBSC- aOR: 6.19, 95% CI:2.52 - 15.21, p-value < 0.001, HBST- aOR: 3.53, 95% CI: 1.09- 11.49, p-value =0.036), having pulmonary hypertension (HBSS - aOR: 19.54, 95% CI:15.61- 24.48, p-value < 0.001, HBSC- aOR: 14.71, 95% CI:6.49 - 33.37, p-value <0.001, HBST- aOR: 9.95, 95% CI: 3.67 - 26.94, p-value < 0.001) and developing VTE on admission (HBSS - aOR: 5.88, 95% CI:4.07 - 8.50, p-value <0.001, HBSC- aOR: 9.75, 95% CI:4.01 - 23.65, p-value <0.001, HBST- aOR: 4.68, 95% CI:1.48 - 14.82, p-value =0.009). Odds of preterm labor in HBSS and HBSC were significantly lower (HBSS - aOR: 0.65, 95% CI:0.57 - 0.75, p-value <0.001, HBSC- aOR: 0.37, 95% CI:0.21 - 0.64, p-value < 0.001). Finally, HbSC disease was associated with higher odds of pre-eclampsia (aOR: 1.66;95% CI: 1.26-2.19, p- value 0.000) and HbSS was associated with statistically lower odds of gestational hypertension (aOR: 0.59, 95% CI: 0.51-0.68, p-value 0.000). Conclusion: HbSC genotype was associated with the highest odds of the development of VTE, pre-eclampsia and requirement for ventilation. Pregnant patients with HBSS had the highest odds of developing pulmonary hypertension. HBSS and HBSC had significantly lower odds of preterm labor.