Sickle cell disease and the incidence and etiology of preterm birth

Medically indicated delivery can be defined as delivery owing to intervention for maternal or fetal well-being-most commonly because of preeclampsia or nonreassuring fetal status. Among the general population of the United States, approximately two-thirds of preterm deliveries are because of spontaneous labor and/or premature rupture of membranes, whereas the remaining one-third are medically indicated. Despite the increased risk of preterm birth among women with sickle cell disease, the specific etiologies have not been described in the medical literature. Without an understanding of the etiologies of preterm birth in women with sickle cell disease, it is difficult to develop preventative strategies.

This study aimed to estimate the incidence and etiologies of preterm births (spontaneous vs medically indicated) in women with sickle cell disease.

This was a retrospective, institutional review board-exempt cohort study of deliveries at >20 weeks' gestation in women with sickle cell disease at Duke University Hospital (2013-2020). We screened pregnancy-linked hospitalizations with International Classification of Diseases-9/10 codes for sickle cell disease (n=373). We excluded cases of pregnancy with <20 weeks' gestation, multiple gestation, or unproven sickle cell disease. We limited inclusion to deliveries within Duke (n=66). We compared the proportion of preterm birth cases between the sickle cell disease cohort and the overall Duke population (n=18,365), and the proportion of spontaneous vs medically indicated preterm births between the sickle cell disease cohort and a racially matched US population.

Of the 66 pregnancies, 65 occurred in patients who self-described as Black (98.5%). There were 60.6% (n=40) term and 39.4% (n=26) preterm births vs 85.9% term (n=15,771) and 14.1% preterm (n=2594) births in the Duke population as a whole. The sickle cell disease cohort was nearly 3 times more likely to deliver preterm than the Duke cohort (risk ratio, 2.79; 95% confidence interval, 2.06-3.77; P<.001). Among the 26 preterm births in the sickle cell disease cohort, 30.8% (n=8) were spontaneous and 69.2% (n=18) were medically indicated. In the US Black population comparison cohort, 65.4% (n=392,984) of preterm births were spontaneous and 34.6% (n=207,614) were medically indicated. The sickle cell disease cohort had 2 times the risk of medically indicated preterm birth compared with the US population cohort (risk ratio, 2.00; 95% confidence interval, 1.55-2.59; P<.001).

Maternal sickle cell disease confers nearly triple the risk of preterm birth, which is twice as likely to be medically indicated.