Evaluation of Stillbirth Among Pregnant People With Sickle Cell Trait

Retrospective cohort study finding both sickle cell trait and disease to be associated with an increased risk of stillbirth, suggesting that sickle cell carriers would benefit from additional risk assessment during pregnancy.

JAMA Network Open

By Silvia P. Canelón, Samantha Butts, Mary Regina Boland in Research

November 24, 2021

Confounders include race and ethnicity and year, and biasing paths connect each of these 2 variables with SCT and stillbirth. Causal paths connect SCT with stillbirth by way of various mediators. Mediators include sickle cell disease (SCD), the number of pain crises before delivery, the number of blood transfusions before delivery, ABO blood type, Rhesus factor, marital status, age, multiple gestation, and delivery episode.

Figure 2. Directed Acyclic Graph With Stillbirth as the Outcome and Sickle Cell Trait (SCT) as the Primary Exposure of Interest.

Alternative Figure 2 Confounders include race and ethnicity and year, and biasing paths connect each of these 2 variables with SCT and stillbirth. Causal paths connect SCT with stillbirth by way of various mediators. Mediators include sickle cell disease (SCD), the number of pain crises before delivery, the number of blood transfusions before delivery, ABO blood type, Rhesus factor, marital status, age, multiple gestation, and delivery episode.

Figure 2. Directed Acyclic Graph With Stillbirth as the Outcome and Sickle Cell Trait (SCT) as the Primary Exposure of Interest.

Abstract

Importance

Relative to what is known about pregnancy complications and sickle cell disease (SCD), little is known about the risk of pregnancy complications among those with sickle cell trait (SCT). There is a lack of clinical research among sickle cell carriers largely due to low sample sizes and disparities in research funding.

Objective

To evaluate whether there is an association between SCT and a stillbirth outcome.

Design, Setting, and Participants

This retrospective cohort study included data on deliveries occurring between January 1, 2010, and August 15, 2017, at 4 quaternary academic medical centers within the Penn Medicine health system in Pennsylvania. The population included a total of 2482 deliveries from 1904 patients with SCT but not SCD, and 215 deliveries from 164 patients with SCD. Data were analyzed from May 3, 2019, to September 16, 2021.

Exposures

The primary exposure of interest was SCT, identified using clinical diagnosis codes recorded in the electronic health record.

Main Outcomes and Measures

A multivariate logistic regression model was constructed to assess the risk of stillbirth using the following risk factors: SCD, numbers of pain crises and blood transfusions before delivery, delivery episode (as a proxy for parity), prior cesarean delivery, multiple gestation, patient age, marital status, race and ethnicity, ABO blood type, Rhesus (Rh) factor, and year of delivery.

Results

This cohort study included 50 560 patients (63 334 deliveries), most of whom were aged 25 to 34 years (29 387 of 50 560 [58.1%]; mean [SD] age, 29.5 [6.1] years), were single at the time of delivery (28 186 [55.8%]), were Black or African American (23 777 [47.0%]), had ABO blood type O (22 879 [45.2%]), and were Rhesus factor positive (44 000 [87.0%]). From this general population, 2068 patients (4.1%) with a sickle cell gene variation were identified: 1904 patients (92.1%) with SCT (2482 deliveries) and 164 patients (7.9%) with SCD (215 deliveries). In the fully adjusted model, SCT was associated with an increased risk of stillbirth (adjusted odds ratio [aOR], 8.94; 95% CI, 1.05-75.79; P = .045) while adjusting for the risk factors of SCD (aOR, 26.40; 95% CI, 2.48-280.90; P = .007) and multiple gestation (aOR, 4.68; 95% CI, 3.48-6.29; P < .001).

Conclusions and Relevance

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

Posted on:
November 24, 2021
Length:
3 minute read, 481 words
Categories:
Research
Tags:
EHR pregnancy sickle cell disease
See Also:
Harnessing electronic health records to study emerging environmental disasters: a proof of concept with perfluoroalkyl substances (PFAS)
A Bayesian Hierarchical Modeling Framework for Geospatial Analysis of Adverse Pregnancy Outcomes
Individual-Level and Neighborhood-Level Risk Factors for Severe Maternal Morbidity