Neonatal Testing for Sickle Cell Diseases—A Historical and Personal Review

Abstract

Testing for sickle cell hemoglobinopathies in the newborn period has gone through several distinct eras that reflect the diagnostic tests available during each period, as well as a changing clinical perception of the necessity and value of such screening for what is essentially an incurable disease (Table 1). From 1930 to 1950, pioneer investigators such as Diggs et al and Scott et al performed classical sickle cell "preps" in groups of black newborns. In the 1960s, investigators, notably Schneider et al and Gilman et al performed hemoglobin electrophoresis for large groups of newborns. However, these were research programs that had little or no clinical coordination or follow-up. In the 1970s, Serjeant et al in Jamaica and myself in New Haven, CT, set up programs of neonatal diagnosis coupled with careful long-term comprehensive follow-up. We are now in an era when neonatal screening for hemoglobinopathies has been recommended or mandated by a number of states. The diagnosis of sickle cell disorders in the neonatal period is complicated because of the presence of large amounts of fetal hemoglobin (Hb F) at birth. Normal adult hemoglobin (Hb A) has two pairs of chemically dissimilar polypeptide chains designated α and β and can be represented as α2β2. Hb S has a pair of chemically altered chains and is designated α2β2s. Fetal hemoglobin, which constitutes 70% to 80% of the hemoglobin of the fetus and newborn, contains γ- instead of β-chains and can be represented as α2α2. γ-Chains are not affected by the sickle cell mutation.