Maternal and fetal risks in patients with sickle cell disease: Results of the retrospective drepamom study Free

Introduction The association between pregnancy and sickle cell disease (SCD) is increasingly common. These two conditions exacerbate each other, leading to a higher rate of vaso-occlusive events and obstetrical complications: preeclampsia, intrauterine growth restriction (IUGR), and preterm births. Despite these challenges, management remains incompletely standardized and requires an individualized approach. The objective of this study was to describe maternal and fetal morbidity and mortality in a cohort of pregnant patients with SCD.

Methods A descriptive, retrospective study was conducted in a single SCD referral center. The study included SCD patients who delivered between January 2013 and January 2023, identified using ICD-10 code D57. Data collected included socio-demographic characteristics, clinical and biological parameters, as well as gestational, neonatal, and postpartum complications.

Results Out of 325 eligible pregnancies, 238 were excluded : 206 due to sickle cell trait, 5 due to other hemoglobinopathies, and 27 due to with missing data. A total of 56 deliveries among 44 patients were analyzed. The median maternal age was 28 years (range 17–41), and 61% had the SS genotype. Before pregnancy, 39% of patients were receiving baseline treatment, mainly hydroxyurea (HU) in 77% of cases (discontinued in 67% within 3 months after pregnancy diagnosis), and transfusion programs in 23% (alone or combined with HU and/or Crizanlizumab). Acetylsalicylic acid was initiated in 46% of pregnancies. Among the 56 pregnancies, 68% required transfusion support, mostly (74%) through a transfusion program following HU discontinuation. HU was continued throughout pregnancy in 4 patients due to transfusion contraindications. Fourteen percent of pregnancies were complicated by IUGR, and 11% by preeclampsia or infections. Regarding sickle cell complications, half of the pregnancies (48%) were complicated by vaso-occlusive crisis (VOC), with 93% requiring hospitalization and 24% admitted to intensive care unit. Nine percent (n=5) experienced acute chest syndrome (ACS), four of whom had a history of ACS. Among the 56 pregnancies, there were 53 live births (two intrauterine fetal deaths and one medical termination of pregnancy), with approximately 30% of births occuring preterm. Most preterm births were induced (73%) due to obstetrical complications (n = 5), sickle cell complications (n = 4), or both (n = 2). Labor induction was required in 60% of deliveries at a mean gestational age of 37.5 weeks. Delivery was spontaneous vaginal in 51%, instrumental vaginal in 6%, and cesarean section in 43%, with maternal indications (scarred uterus or vaso-occlusive event) being the main cause for cesarean. Postpartum hemorrhage occurred in 24% of cases, with 46% classified as severe. The mean birth weight was 2,647 g at an average gestational age of 36.8 weeks. Five newborns presented with congenital anomalies (laryngeal stenosis, craniosynostosis, periventricular pseudocysts, metatarsus varus, pyelectasis), although none were exposed to HU in utero after 14 weeks. Two fetal deaths in utero (4%), one medical termination of pregnancy (2%) and 3 neonatal deaths (6%) were reported. Of the 23 placentas for which histological analysis was available, 61% showed ischemic lesions. During postpartum, 11% of patients experienced VOC, requiring hospitalization in 50% of these cases. Univariate analysis showed no significant difference in materno-fetal complications across genotypes. Patients on transfusion programs had significantly fewer VOCs (9/28 vs. 16/26; p=0.03), although this did not reduce obstetrical complications (11% vs. 8% for preeclampsia; 14% vs. 12% for IUGR), possibly due to small sample size. Acetylsalicylic acid did not reduce the prevalence of placental abnormalities (p=1) nor increase the risk of postpartum hemorrhage (p=0.637).

Conclusion Pregnancy in sickle cell disease carries significant maternal and fetal risks and requires management in specialized centers. Transfusion programs reduce the risk of VOC but must be balanced against alloimmunization and delayed hemolytic transfusion reactions risks, which is prevalent in this population, highlighting the need to reconsider therapeutic alternatives, including HU, in cases of transfusion deadlock.