Prenatal anemia may be mediator linked to pregnancy risk in people with sickle cell disease
Click Here to Manage Email Alerts
Odds of several adverse pregnancy outcomes appeared strikingly similar between pregnant people with anemia and pregnant people with sickle cell disease, according to a study published in JAMA Network Open.
Deliveries among both groups of people — all of whom identified as Black — had comparable odds particularly of complications associated with ischemia, cardiovascular stress or abnormal placentation, results showed.
The preliminary data suggest prenatal anemia may be a mediator associated with some of the increased risk for severe maternal morbidity and adverse pregnancy outcomes among pregnant people with sickle cell disease, researchers wrote.
Background, methodology
Pregnancies among patients with sickle cell disease are considered high risk; however, it remained unknown whether prenatal anemia, which can be treated with red blood cell transfusions, is a mediator linked to pregnancy complications.
“At present, the only treatment available for pregnant people with sickle cell disease is red blood cell transfusions, which may be given episodically (on demand) or chronically,” Macy L. Early, BA, medical student in the division of hematology, department of medicine at Johns Hopkins University School of Medicine, and Lydia H. Pecker, MD, director of the young adult clinic at the Sickle Cell Center for Adults at Johns Hopkins, wrote in a statement to Healio. “There are also investigational and an approved drug that treat anemia in sickle cell disease. ASH’s sickle cell disease transfusion guidelines address indications for chronic transfusion but, of course, anemia alone is not an indication for therapy in pregnant people with sickle cell disease. By comparing people with sickle cell disease to controls with anemia, we wanted to start considering the extent to which the anemia alone might drive adverse pregnancy outcomes.”
The researchers used National Inpatient Sample data from 2012 to 2018 to analyze 764,455 delivery admissions among patients who identified as Black (mean age at delivery, 27 years, standard deviation, 6.08 years), including 3,200 with sickle cell disease, 34,808 with anemia and 726,447 who served as controls. Most women (65.4%) had public health insurance.
In a separate study of 5.4 million deliveries in the sample, published simultaneously in JAMA Network Open, the researchers found higher risk for severe maternal morbidity among people with sickle cell disease vs. those without the disease, particularly with regard to thrombolic events, organ failure and death. Moreover, racial disparities explained a median 28.9% of the higher risk in deliveries among people with sickle cell disease.
Results
In the current study, patients with sickle cell disease had higher rates of composite severe maternal morbidity (5.9%; 95% CI, 5.1-6.8) than those with anemia (2.1%; 95% CI, 2-2.3) and those who served as controls (1.1%; 95% CI, 1-1.1), as well as higher rates of mortality per 10,000 deliveries (13 deaths; 95% CI, 4.9-35 vs. 0.9 deaths; 95% CI, 0.3-2.8 vs. 1.2 deaths; 95% CI, 1-1.5).
Compared with the control group, adjusted odds ratio (aOR) of severe maternal morbidity appeared higher for sickle cell disease group (aOR = 5.51; 95% CI, 4.71-6.45) and anemia group (aOR = 2; 95% CI, 1.84-2.17). But researchers noted that, between the sickle cell disease and anemia groups, the CIs of aORs overlapped for several complications linked to ischemia or abnormal placentation, such as eclampsia (aOR = 2.74; 95% CI, 1.51-4.96 vs. 1.4; 95% CI, 1.08-1.81) and obstetric shock (aOR = 4.1; 95% CI, 2.26-7.44 vs. 2.03; 95% CI, 1.53-2.7). Risk ratios of these complications for the sickle cell disease vs. anemia groups ranged from 1 to 2.1, including 1.76 (95% CI, 0.93-3.32) for eclampsia.
The sickle cell disease group also had higher rates and aORs of complications associated with thrombosis or sickle cell disease-specific pathologies. Among them, acute respiratory distress syndrome, including acute chest syndrome, occurred in 56 of 3,144 deliveries (1.8%) in the sickle cell disease group vs. 122 of 34,686 deliveries (0.4%) in the anemia group, for a risk ratio of 4.99 (95% CI, 3.65-6.84).
“We were surprised by the extent to which complications could be categorized into two groups: those for which pregnant people with sickle cell disease and those with anemia had similar risk, and those for which the risk was significantly elevated in people with sickle cell disease,” Early and Pecker told Healio. “This raises the possibility that the anemia of sickle cell disease in pregnancy drives certain adverse outcomes, while the thrombophilia, hemolysis and inflammation drive others.”
The associations presented in the study are limited by the administrative nature of the database, they noted.
Next steps, implications
A multicenter clinical study of pregnant people with sickle cell disease and those with anemia is needed to directly compare exposures and outcomes, according to Early and Pecker.
“The ways in which sickle cell disease pathophysiology, including chronic anemia, affects what we consider to be the ‘normal’ physiologic adaptations to pregnancy are unknown,” they told Healio. “Elucidating the physiology of sickle cell disease pregnancy can advance our study and use of interventions to improve outcomes.”
References:
- Early ML, et al. JAMA Netw Open. 2023;doi:10.1001/jamanetworkopen.2022.54545.
- Early ML, et al. JAMA Netw Open. 2023;doi:10.1001/jamanetworkopen.2022.54552.
Collapse
Read more about
Click Here to Manage Email Alerts