Newborn Screening for Sickle Cell Disease and Other Hemoglobinopathies

Hemoglobinopathies represent one of the major health problems in the United States and constitute the most common genetic disorders in some populations. Sickle cell diseases (sickle cell anemia, sickle cell—hemoglobin C, and sickle cell—β-thalassemia) alone affect about one of every 400 American black newborns. These and other hemoglobinopathies are common in persons of African, Mediterranean, Asian, Caribbean, and South and Central American origins as well. Although the technology to screen infants for hemoglobinopathies in the newborn period has been available for many years, widespread adoption of screening has not occurred. Reasons have included lack of a demonstrated improvement in outcome with early diagnosis, uncertainty about who to test, technical difficulties caused by the high level of fetal hemoglobin in the neonate, and questions about obligations to those identified as carriers. For at least 20 years, it has been known that children with sickle cell anemia have an increased susceptibility to severe bacterial infection, particularly due to Streptococcus pneumoniae. The risk of major infection with this organism is greatest in the first three years of life and can occur as early as 4 months of age. This infection may be the first clinical manifestation of disease and carries a case fatality rate as high as 30%. Acute splenic sequestration crisis, another catastrophic event, also contributes to mortality in infancy. Data are now available documenting a reduction of morbidity and mortality through early diagnosis and immediate entry into programs of comprehensive care, including penicillin prophylaxis. Early diagnosis of hemoglobinopathies is facilitated by newborn screening. Screening has the capability of reaching infants who might otherwise be lost to the health care system or delayed in their entry into it. Neonatal testing to identify infants with major sickling diseases allows prompt institution of ongoing care, including the provision of effective prophylaxis. It is unclear whether presymptomatic interventions offer significant advantage to infants with other hemoglobinopathies (eg, hemoglobin E-β-thalassemia and homozygous β- and α-thalassemias). Identification by newborn screening may, however, provide natural history data and/or allow testing of potential interventions. To examine questions surrounding the issue of neonatal screening and to enhance understanding among scientists, health care providers, and the public at large, the National Heart, Lung, and Blood Institute and the National Institute of Child Health and Human Development of the National Institutes of Health (NIH); the Genetic Disease Services Branch, the Division of Maternal and Child Health, the Bureau of Health Care Delivery and Assistance of the Health Resources and Services Administration; and the NIH Office of Medical Applications of Research convened the NIH Consensus Development Conference on Newborn Screening for Sickle Cell Disease and Other Hemoglobinopathies April 6 through 8, 1987. For VA days, experts in the field presented their findings and an audience that included health professionals, parents, patients, and other interested persons discussed the issues. A consensus panel representing the fields of biochemistry, genetics, pediatrics, obstetrics, hematology, public health, nursing, law, epidemiology, and counseling considered the scientific evidence and developed answers to the following questions: Are programs for screening the newborn for sickle cell disease effective in decreasing morbidity and mortality? What are the techniques of screening and what are their efficacies? What are the major factors to be considered, including benefits and risks, in conducting newborn screening programs? What are the optimal methods of follow-up and management of infants identified with hemoglobinopathies (disease and carriers)? What future research directions are indicated?