Increased Risk of Stillbirth for Pregnant Women With Sickle Cell Trait

New research indicates an increased risk of stillbirth for delivering mothers who have the sickle cell trait (SCT), but not sickle cell disease (SCD).

A team, led by Mary Regina Boland, MA, MPhil, PhD, FAMIA, Assistant Professor of Informatics in Biostatistics and Epidemiology, University of Pennsylvania, evaluated the association between sickle cell trait and a stillbirth outcome.

The Difference Between Sickle Cell Trait and Disease

While investigators have a solid understanding on the relationship between pregnancy complications and sickle cell disease, there is far less known on this risk among individuals with sickle cell trait. This discrepancy in knowledge is largely because of a lack of clinical research among sickle cell carriers because of low sample sizes and disparities in research funding.

Individuals with 1 abnormal allele of HbS have sickle cell trait, while patients with 2 abnormal alleles have sickle cell disease.

“Sickle cell trait is not considered a disease state because many sickle cell carriers have at least 50% normal adult hemoglobin8 and are asymptomatic,” the authors wrote. “However, it is possible for people with SCT to experience sickling of red blood cells under severe hypoxia, dehydration, and hyperthermia.”

A Fresh Look at Data

In the retrospective cohort study, the investigators examined data on deliveries at 4 quaternary academic medical centers within the Penn Medicine health system between January 1, 2010 and August 15, 2017. There was a total of 2482 deliveries during this time period from 1904 patients with sickle cell trait, but not sickle cell disease. There was also 215 deliveries from 164 patients with sickle cell disease included in the data.

The team used a multivariate logistic regression model to assess the risk of stillbirth using a number of risk factors, including sickle cell disease, numbers of pain crises and blood transfusions prior to delivery, delivery episode as a proxy for parity, prior cesarean delivery, multiple gestation, patient age, marital status, race and ethnicity, ABO blood type, Rhesus factor, and year of delivery.

Outcomes for Deliveries

The majority of deliveries were from individuals aged 25-34 years (58.1%; n = 29,387) and single at the time of delivery (55.8%; n = 28,186).

Other trends were found as well.

For example, 47% (n = 23,777) of deliveries were Black or African American individuals, 45.2% (n = 22,879) had ABO blood type, and 87% (n = 44,000) were Rhesus factor positive.

However, from the 50,560 patients and 63,334 deliveries, only 4.1% (n = 2068) of patients identified had a sickle cell gene variation.

Using a fully adjusted model, the investigators found sickle cell trait was linked to an increased risk of stillbirth (aOR, 8.94; 95% CI, 2.48=280.90; P = 0.007), as well as multiple gestation (aOR, 4.68; 95% CI, 3.48-6.29; P <0.001).

“The results of this large, retrospective cohort study indicate an increased risk of stillbirth among pregnant people with SCT,” the authors wrote. “These findings underscore the need for additional risk assessment during pregnancy for sickle cell carriers.”

The study, “Evaluation of Stillbirth Among Pregnant People With Sickle Cell Trait,” was published online in JAMA Network Open.