Trends and Disparities in Sickle Cell Disease-Related Mortality in the United States from 1999 to 2020: Insights from the CDC Wonder Database

Introduction

Sickle cell disease (SCD) is a disorder characterized by HbS caused by a single gene mutation. It is the most common monogenic disorder. Considering the increased risk of fatality associated with SCD, it is essential to determine trends in sickle cell disease-related mortality and identify high-risk populations.

Methods

We extracted age-adjusted mortality rates (AAMR) per 100,000 population from 1999 to 2020 from the CDC Wide-ranging ONline Data for Epidemiologic Research (WONDER) database. SCD was assigned as the contributing cause of death using the ICD-10 codes D57.0 (sickle-cell anemia with crisis), D57.1 (sickle-cell anemia without crisis), D57.2 (double heterozygous sickling disorders), and D57.8 (other sickle-cell disorders). AAMRs were stratified by year, gender, race, and geographical distribution. Annual percentage change (APC) in AAMR was determined via Joinpoint regression using the Joinpoint Regression Program (V 5.1.0, National Cancer Institute).

Results

From 1999 to 2020, a total of 17,711 SCD-related deaths were reported. The AAMR remained largely unchanged from 1999 to 2018 (APC: -0.03) before a sharp increase was observed from 2018 to 2020 (APC: 8.20). The AAMR increased steadily for females throughout the study period (APC: 0.34) but decreased for males from 1999 to 2018 (APC: -0.36). However, an increase was observed for males from 2018 to 2020 (APC: 10.97). Upon stratification by census region, the highest AAMR was observed in the South (0.41), followed by the Northeast (0.25), the Midwest (0.20), and the West (0.11). The AAMR in the Midwest and the West remained constant from 1999 to 2020 (APC Midwest: 0.21; West: 0.15). It also remained unvaried in the Northeast and the South from 1999 to 2018 (APC Northeast: -0.37; South: 0.03), before increasing from 2018 to 2020 (APC Northeast: 11.27; South: 9.66). The AAMR in urban areas (0.27) remained higher than in rural areas throughout the study period. It remained constant in urban areas (APC: 0.13) but increased steadily in rural areas (APC: 0.96) from 1999 to 2020. States with the highest AAMR were the District of Columbia, (1.19), South Carolina (0.81), and Mississippi (0.80), whereas those with the lowest included Oregon (0.02), Washington (0.05), and Iowa (0.06). The overall AAMR for New Mexico and Utah was deemed to be unreliable.

Conclusions

Given the observed increase in sickle cell disease-related mortality from 2018 to 2020, it is crucial to direct targeted interventions toward high-risk populations, including males, individuals in the South and Northeast, and those residing in urban counties. It is equally important to critically analyze trends, as mortality rates are rising in rural counties. Therefore, a comprehensive analysis of screening, treatment, and management techniques across all regions is essential to address and mitigate the rising sickle cell disease-related mortality.