Newborn Screening for Sickle Cell Disease and Thalassemia

Abstract

Importance: Hemoglobin disorders are a considerable public health issue with more than 500 000 affected infants born annually worldwide. First introduced in the 1970s, newborn screening (NBS) for sickle cell disease (SCD) was included in the Recommended Uniform Screening Panel (RUSP) in 2006, a successful public health promotion and prevention practice that has led to improved childhood survival. Although SCD is the primary target, the screening process also detects many other hemoglobinopathies.

Observations: NBS programs, administered by individual states, vary in their practices for hemoglobinopathy screening, creating health inequities and compromising public health efforts. There is a lack of uniformity in the choice of primary screening test, reporting, and follow-up of abnormal results, exacerbated by inconsistent access to genetic confirmation. Consequently, newborns diagnosed through protein-based screening alone may have diverse genotypes that alter the clinical expression of hemoglobinopathies. This Special Communication considers how the universal adoption of molecular testing for hemoglobinopathy newborn screening can overcome these current shortcomings. Simultaneously, the considerable challenges of primary screening with molecular methods and how these can be overcome are evaluated. Screening with targeted genetic testing of the hemoglobin genes (HbA1, HBA2, HBB) is especially well suited to hemoglobinopathies because there exists an extensive database of variants for the prediction of pathogenicity, averting the need for secondary or multiple testing. Importantly, it would eliminate the health disparities created by location and health insurance on the access to confirmatory testing and facilitate timely referral for definitive care. Standardization of the screening platform with diagnostic specificity has vast implications for public health surveillance and resource allocation. The adoption of molecular testing requires bringing new technology online, training and changes to workflow, potentially increased cost, and concerns for genetic data protection. Some of these barriers can be overcome using high-throughput methods with the potential to multiplex with other disease conditions that use genetic testing for primary screening through the consolidation of platforms.

Conclusions and relevance: The time has come for a paradigm shift in newborn screening for hemoglobinopathies through the adoption of universal molecular genetic testing.