Study Identifies Potential Trends in Pediatric Sickle Cell Mortality

Kristina Lai, MPH

A new population-based cohort study of pediatric patients with sickle cell disease found that mortality trends have largely shifted from bacterial infections as a cause to other associated complications, subsequent treatments, or comorbidities.

The study also reported that mortality risk increased as patients began transition to adult care.

In the largest and most recent study of mortality in this population, Kristina Lai, MPH, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta (CHOA), and colleagues reviewed and categorized morality using CHOA’s Sickle Cell Clinical Database for deceased patients.

“Mortality rates and causes of death in children with sickle cell disease have changed significantly over the past several decades,” the team wrote. “With ongoing improvements in standards of care, modern mortality estimates must be updated.”

They obtained information on demographics, sickle cell disease genotype, data and age of death, healthcare utilization, hydroxyurea use, chronic transfusion therapy, and bone marrow transplant. They further abstracted cause of death and history of significant comorbidities from medical records.

Overall, Lai and colleagues assessed 3698 patients who were seen from June 2010-June 2020, which accounted for 19,998 person-years.

Of that total, 45 patients (178 person-years) died. The majority (n = 37) were sickle cell anemia genotypes (Hb SS or Hb S β0 thalassemia), followed by Hb SC (n = 5), and Hb S β+ thalassemia (n = 3).

In terms of patient demographics, 53% were female, and the average age at death was 12.8 years.

Up to 21 (46.7%) of the deceased patients had been treated with hydroxyurea at some point, and 11 (24.4%) had been treated with chronic transfusion therapy.

“During this 10-year period, the crude death rate was 2.3 per 1,000 person-years,” the investigators continued. “The majority of deaths (62%, n=28) were attributable SCD-related causes and corresponded to a cause-specific mortality rate of 1.40 per 1,000 person-years.”

These causes included an acute illness related to sickle cell disease (n = 12), acute bacterial infections (n = 3), complications related to treatment (procedure-related, n = 1; drug-induced hemolytic anemia, n = 2), and complications of bone marrow transfusion (n = 1).

The further noted that the remaining 38% of deaths were attributed to complex non-sickle cell disease comorbidities (n = 16) or accidental trauma (n = 17). Thus, the non-sickle cell disease mortality rate was calculated to 0.85 per 1,000 person-years.

“In comparison, the mortality rate for African American persons age <22 in Georgia from 2009-2018 was 0.9 per 1,000 person-years.,” they wrote.

The non-sickle cell disease comorbidities included cancers (n = 3), autoimmune disorders (n= 2), and congenital heart disease (n = 6).

And finally, their analysis showed that of the 10 patients who died at age >19, 8 had either recently transitioned to adult care or had a documented transition plan.

Lai and her team acknowledged that the single healthcare system approach was a major limitation of the study. Therefore, they indicated that future analyses should focus on expanding the cohort to include data from death certificates and the US Centers for Disease Control (CDC) National Death Index.

The study, “10-Year Mortality in Patients with Sickle Cell Disease from a Large Population-Based Cohort,” weas published in Blood.