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Copyright 1998 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.1998American Medical AssociationThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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SICKLE CELL disease (SCD) is an autosomal recessive disorder characterized by production of abnormal (sickle) hemoglobin, resulting in anemia, susceptibility to pneumococcal and other infections, pain, stroke, and multiple organ dysfunctions. The most common types include hemoglobin SS (homozygous) disease, sickle cell–hemoglobin C disease, and the sickle beta-thalassemia syndromes.1 A randomized controlled trial published in 1986 indicated that daily oral penicillin prophylaxis reduced the incidence of serious infection in young children with SCD and led to widespread adoption of newborn screening programs for SCD.2 To study the effectiveness and utilization of prevention programs among large populations of infants with SCD, several newborn screening programs in the United States are now attempting to determine rates of complications and actual use of early medical interventions (e.g., penicillin prophylaxis and pneumococcal vaccination). This report focuses on recent mortality in California, Illinois, and New York. In California and Illinois, mortality from all causes among black children born during 1990-1994 with SCD was slightly less than overall mortality for all black children born in the same time period.
All newborns in California, Illinois, and New York are screened for hemoglobinopathies. Health departments implemented screening programs in New York in 1975, Illinois in 1989, and California in 1990. For this investigation, SCD was defined as any clinically significant sickle hemoglobinopathy in an infant born during 1990-1994. In California and Illinois, identifying variables from SCD databases were matched with computerized records of state-specific death certificates for 1990-1995. In New York, all SCD-related deaths among children aged <3 years listed in state vital records for 1990-1994 were matched with the state SCD database. Additional follow-up extending through 1997 was available in California and Illinois: local physicians (i.e., through surveys) and public health nurses informed the respective state health department about the circumstances of SCD-related deaths; such information was not available in New York. Mortality rates per person-year were calculated assuming complete death ascertainment through December 31, 1994, in New York and through December 31, 1995, in California and Illinois.
During 1990-1994, a total of 2487 children with presumed or confirmed SCD were identified by the three newborn screening programs. Excluding two deaths of children presumably born in other states, 27 deaths were reported among children with SCD; 20 death certificates provided causes that included SCD or other conditions related to SCD. The median age at death for the 20 infants who had SCD-related deaths was 22 months (range: 2-53 months). Mortality rates for each state were similar. In California and Illinois, where mortality for all causes was ascertained, by the end of 1995 the cumulative mortality rate was 1.5 per 100 black children with SCD born during 1990-1994. The equivalent cumulative mortality rate for all black children born during this period in California and Illinois was 2.0 per 100 black newborns, based on approximate age-coded data in national multiple-cause mortality files.3
Mortality data was available until the third birthday for the subgroup of 768 children with presumed or confirmed hemoglobin SS disease born during 1990-1991 in New York and during 1990-1992 in California and Illinois. Of these 768 children, 1.0% died as a result of SCD-related causes during the first 3 years of life (0.35 per 100 person-years, based on 2258 person-years [95% confidence interval=0.15-0.70 per 100 person-years]). The rate of compliance with penicillin prophylaxis was unknown; an investigation of risk factors is being conducted to analyze this and other factors in relation to death and other serious complications. Information about risk factors will be obtained through parental and physician surveys.
G Cunningham, MD, F Lorey, PhD, Genetic Disease Br, California Dept of Health Svcs. S Kling, MA, K Soper, MA, F Urso, JD, Div of Health Assessment and Screening, Illinois Dept of Public Health. K Harris, MBA, V Konopka, MA, K Pass, PhD, Wadsworth Center, New York State Dept of Health. R Choi, Public Health Institute. Birth Defects and Genetic Diseases Br, Div of Birth Defects and Developmental Disabilities, and Office of Genetics and Disease Prevention, National Center for Environmental Health, CDC.
The findings in this report indicate low mortality rates for children with SCD born during the early 1990s in geographic areas in which infants with the condition are identified soon after birth. Early diagnosis is an important component of comprehensive medical care for affected children.1,4 In a study of U.S. death certificates for 1968-1992, mortality among black children aged 1-4 years who had SCD declined significantly.5 This trend occurred at the same time as the establishment of newborn screening programs, more comprehensive care and parental education, widespread acceptance of penicillin prophylaxis after publication of the randomized trial in 1986, and new vaccinations.
Although the mortality rate for children with hemoglobin SS disease described in this report is lower than comparable rates in earlier studies, comparisons between these mortality rates and those from clinical studies, the Cooperative Study of SCD, and national death certificates must be interpreted cautiously because of differences in study design and ascertainment of deaths.5-7 One limitation of this investigation is that deaths outside the three states would not have been ascertained. Underascertainment of deaths also could have occurred through errors in matching or reporting of vital statistics. This study was population-based, and mortality rates were relatively stable because of the large number (2487) of young children with SCD.
In Maryland, the mortality rate for black children with SCD was comparable to, or lower than, the mortality rate for all black children during 1985-1994.8 Underascertainment of SCD among severely ill neonates could account for this finding, but ill children in neonatal intensive-care units usually are screened for SCD. In California, Illinois, New York, and Maryland, comprehensive medical care and public health interventions may have contributed to the observed reduction in premature mortality from all causes.
Newborn screening follow-up studies are useful for evaluating the prevention effectiveness of public health programs, which is an essential component of applying genetic technology to disease prevention.9 Follow-up studies can determine whether public health programs that are widely implemented have the prevention impact that the randomized trials predicted. Continued evaluation over time of comparable data for hemoglobinopathies and other newborn conditions can provide epidemiologic evidence of the clinical value of screening programs for these conditions. More detailed analysis of risk factors for adverse outcomes among children who have SCD also will assist public health agencies with targeting prevention programs for specific high-risk groups.
Mortality Among Children With Sickle Cell Disease Identified by Newborn Screening During 1990-1994—California, Illinois, and New York. JAMA. 1998;279(14):1059–1060. doi:10.1001/jama.279.14.1059