Improved survival of children and adolescents with sickle cell disease

Abstract

The survival of young children with sickle cell disease (SCD) has improved, but less is known about older children and adolescents. We studied the Dallas Newborn Cohort (DNC) to estimate contemporary 18-year survival for newborns with SCD and document changes in the causes and ages of death over time. We also explored whether improvements in the quality of medical care were temporally associated with survival. The DNC now includes 940 subjects with 8857 patient-years of follow-up. Most children with sickle cell anemia (93.9%) and nearly all children with milder forms of SCD (98.4%) now live to become adults. The incidence of death and the pattern of mortality changed over the duration of the cohort. Sepsis is no longer the leading cause of death. All the recent deaths in the cohort occurred in patients 18 years or older, most shortly after the transition to adult care. Quality of care in the DNC has improved over time, with significantly more timely initial visits and preventive interventions for young children. In summary, most children with SCD now survive the childhood years, but young adults who transition to adult medical care are at high risk for early death.

Figure 1

Temporal changes in causes of death in children with sickle cell disease. Three categories of death are shown on the y-axis: deaths due to acute chest syndrome (ACS) and multiorgan failure syndrome (MOFS), deaths due to sepsis, and deaths of all other causes. Together, deaths due to ACS and MOFS are now more common than fatal sepsis. Notably, no member of the cohort has died from Haemophilus influenzae type b sepsis () or Streptococcus pneumoniae sepsis () since the availability of the protein-conjugate vaccine against either bacterium (dotted lines).

Figure 2

Survival of children with sickle cell disease. (A) Overall survival (all-cause mortality) for children with sickle cell anemia and sickle β⁰-thalassemia. Estimated survival at 18 years of age is 93.9% (95% CI: 90.3-96.2). Numbers above the x-axis indicate the number of subjects at risk at each age. (B) Overall survival (all-cause mortality) for children with sickle hemoglobin C disease and sickle β⁺-thalassemia. Estimated survival at 18 years of age is 98.4% (95% CI: 94.4-99.5). Numbers above the x-axis indicate the number of subjects at risk at each age. (C) Trends in overall survival for children with sickle cell anemia and sickle β⁰-thalassemia by cohort era. Cohort eras are defined by year of birth (1983-1990, 1991-1999, and 2000-2007). (D) Comparison of overall survival for children with sickle cell anemia and sickle β⁰-thalassemia by cohort. We compare the first and last thirds of the Jamaican cohort, the infant cohort of the Cooperative Study of Sickle Cell Disease, the East London Cohort, and the first and last eras of the Dallas Newborn Cohort. Note that the y-axes (fraction surviving) of all panels do not begin at 0.

Figure 3

Measures of quality medical care for children with sickle cell disease. (A) The age when prophylactic penicillin was first prescribed for subjects with sickle cell anemia and sickle β⁰-thalassemia. (B) The age at first visit to our center by year of birth for all cohort subjects. (C) The age at first dose of 7-valent protein-conjugated pneumococcal vaccine (PCV-7) for all cohort subjects. The time to first PCV-7 in patients born before 2000 reflects only the age of patients at the time the vaccine became available (dotted line), not quality of care. (D) The age at first dose of 23-valent polysaccharide pneumococcal vaccine (PPV-23) for all cohort subjects. For all panels, boxes show the median and the 25th and 75th percentiles, and whiskers show the 5th and 95th percentiles. Note the logarithmic scale (base 2) of the y-axes in all panels.