Mortality Trends and Causes of Death in Persons with Sickle Cell Disease in the United States, 1979-2014
Authors: Payne Amanda B. , Mehal Jason M. , Chapman Christina , Haberling Dana L. , Richardson Lisa C. , Bean Christopher J. , Hooper William C. 
Published: April 2021

Abstract
Background: Sickle cell disease (SCD)-related mortality is a significant cause of mortality among Blacks in the United States. Several clinical interventions, such as penicillin prophylaxis, vaccination, and hydroxyurea, have decreased SCD-related mortality over time. This report investigates changes in the causes of death (COD) associated with SCD-related mortality over time and among age groups and compares SCD-related deaths to non-SCD-related deaths to identify changes in the burden of specific COD in order to inform future public health improvement efforts.
Methods: SCD-related deaths were examined using the 1979-2014 US multiple COD mortality data. SCD-related deaths were identified as deaths for which an International Classification of Disease 9th revision (ICD-9) or ICD-10 code for SCD (282.6 for ICD-9; D57.0, D57.1, D57.2, D57.8 for ICD-10) was listed anywhere on the death record. Age-specific annual and average annual SCD-related death rates were calculated as the number of deaths per 100,000 corresponding population, with the bridged-race intercensal estimates of the US resident population as the denominator. Because death from SCD is a rare event in races other than Black, the analysis focused on decedents of Black race. Underlying and contributing COD codes were categorized according to their ICD-9 or ICD-10 codes into 20 groups relevant to SCD outcomes, including acute infection complications, cerebrovascular complications, splenic complications, and renal complications. To compare SCD-related deaths to non-SCD deaths, death records not listing an ICD-9 or ICD-10 code for SCD were randomly selected in a 1:1 ratio; non-SCD deaths were matched to SCD deaths by race, sex, age group, year of death, and region of residence.
Results: From 1979-2014 there were 23,226 SCD-related deaths reported in the US. The median age at death increased from 28 years in 1979 to 43 years in 2014. The SCD-related average annual death rate trends shifted by time period across various age groups. The average annual SCD-related death rate among children &lt;5 years of age declined from 2.05/100,000 in 1979-1989 to 0.35/100,000 in 2011-2014 (p&lt;.0001). Conversely, the rate among adults ≥60 years of age increased from 1.20/100,000 in 1979-1989 to 1.69/100,000 in 2000-2014 (p&lt;0.0001). Changes in the frequency of various underlying and contributing COD among SCD-related deaths reflects the success of clinical interventions. During the first time period (1979-1989) acute cardiac and infection complications were the most common underlying and contributing COD. In contrast, chronic cardiac complications was most commonly listed as the underlying or contributing COD during the last time period (2010-2014) (Figure 1). The underlying and contributing COD listed among SCD-related deaths also differed by age group (Figure 2). The most common COD among deaths occurring at &lt;5 years of age was acute infection. The most common COD among deaths occurring at ≥60 years of age was cardiac complications. While clinical interventions have shown effect, compared to non-SCD-related deaths, SCD-related deaths remained more likely to be related to COD, such as acute infections, cerebrovascular complications, and renal complications (Figure 3).
Conclusions: While utilizing death certificate data alone may misclassify some deaths, the utilization of national data allows the assessment of trends in mortality over several decades and provides information regarding SCD-related mortality trends nationwide. The data presented indicate interventions to prevent acute complications of SCD appear effective during the study period. More research regarding prevention and treatment of chronic complications of SCD is necessary, as persons with SCD are living longer and are more likely to die of chronic complications of their disease.

Disclosures
No relevant conflicts of interest to declare.