Cardiopulmonary complications during pregnancy as a risk factor for cesarean delivery in a two center, sickle cell disease pregnancy cohort

Abstract Introduction: Pregnancy is high risk in sickle cell disease (SCD) with increased risk of pre-term and cesarean delivery. Little is known about the circumstances surrounding delivery in SCD pregnancy. This study aimed to use a 2-center SCD pregnancy cohort to describe labor-related data and determine which SCD-specific pregnancy complications are risk factors for emergent cesarean deliveries. Methods: This SCD pregnancy cohort includes deliveries at Mt. Sinai Hospital, Toronto (1990-2017) and Johns Hopkins Hospital (2000-2021). The dataset includes pre-pregnancy comorbidities and SCD complications before and during pregnancy, delivery, and fetal outcomes. We included the first recorded pregnancy of patients in the sample and excluded multifetal gestations. We first grouped patients by delivery mode. We analyzed whether mode of delivery differed by the following: hydroxyurea use before and during pregnancy, chronic transfusion therapy (CTT) during pregnancy, SCD complications before and during pregnancy, complications during labor, and new or worsening comorbidities during pregnancy. We used chi-square tests for categorical variables and Kruskal-Wallis tests for continuous variables. A p-value<0.05 defined significance. In subgroup analysis, we examined pregnancy outcomes in those with sickle cell anemia (HbSS or HbSβ0-thalassemia). Results: There were 198 singleton pregnancies. The cohort's median (interquartile range (IQR)) age was 26(22,31) years, 54% had HbSS, 21% took hydroxyurea before pregnancy, and 19% were chronically transfused during pregnancy. The median (IQR) gestational age was 38.2(36.6,39.1) weeks. The median (IQR) parity was 0(0,1). Labor-related data were available for 195 pregnancies. Among 195 pregnancies, labor was induced in 87, spontaneous in 78, and 30 had emergent or elective cesarean deliveries without spontaneous or induced labor. Delivery data were available for 198 pregnancies. Among 108 vaginal deliveries, 93 were spontaneous vaginal delivery (SVD), 12 were vacuum-assisted and 3 were forceps-assisted. There were 89 cesarean deliveries, 69 emergent and 20 elective. There was one dilation and evacuation. Twelve subjects had a history of cesarean delivery and had repeat cesarean delivery; ten were elective and two were emergent. The rate of cesarean delivery was 45% (89/198 pregnancies). We compared pregnancy outcomes among SVD, elective and emergent cesarean deliveries(n=182). No preconception SCD complications or labor complications were associated with delivery mode. Cardiac comorbidities (CHF, cardiomyopathy, cardiomegaly and hypertension) during pregnancy were risk factors for emergent cesarean delivery(10/69 emergent cesarean vs 2/93 SVD vs 3/20 elective cesarean, p=0.015). Pulmonary complications during pregnancy, including acute chest syndrome (ACS) and pulmonary hypertension, were risk factors for emergent cesarean delivery(20/69 emergent cesarean vs 17/93 SVD vs 7/20 elective cesarean, p=0.035). In subgroup analysis with sickle cell anemia, no complications during pregnancy remained significant. Emergent cesarean delivery was associated with adverse birth outcomes, including fetal resuscitation (24/69 emergent cesarean vs 12/88 SVD vs 6/19 elective cesarean, p=0.006) and admission to NICU (21/69 emergent cesarean vs 9/89 SVD vs 4/19 elective cesarean, p=0.006). Delivery outcomes were not associated with hydroxyurea use before or during pregnancy(n=182). We compared subjects who received CTT during pregnancy(n=32) to those who did not(n=150). There was no between group difference in SVD(17/32 CTT vs 76/150 not CTT, p>0.05) or emergent cesarean(8/32 CTT vs 61/150 not CTT, p=0.097). CTT was associated with elective cesarean delivery(7/32 CTT vs 13/150 not CTT, p=0.030) and there was no difference in repeat cesarean(4/7 elective cesarean CTT vs 6/13 elective cesarean not CTT, p>0.05). This could reflect anticipatory care as CTT during pregnancy is an indicator of disease severity. Conclusion: Cesarean deliveries are morbid with higher risk of hysterectomy and NICU admission. Current studies list emergent cesarean deliveries as a risk factor for SCD postpartum complications, specifically ACS. In this cohort with a 45% cesarean delivery rate, risk factors for emergent cesarean delivery include cardiopulmonary complications during pregnancy, particularly ACS. This encourages further study into whether preventing cardiopulmonary complications during SCD pregnancy alters cesarean section rates.

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