Clinical Utility of the Addition of Molecular Genetic Testing to Newborn Screening for Hemoglobinopathies for Confirmation of Alpha-Thalassemia Trait

Hemoglobinopathies are commonly detected by newborn screening (NBS). One of the most difficult to accurately diagnose is alpha-thalassemia, which is indicated by the presence of hemoglobin (Hb) Barts on NBS. This mixed methods study incorporated (1) an implementation and quality improvement project to demonstrate the clinical utility of genetic testing added to standard procedures for likely alpha-thalassemia trait and (2) a qualitative study to determine the related educational needs of primary care providers (PCPs). During a two-year period, we attempted to perform alpha-globin genetic testing for all newborns with an abnormal NBS result (an "FA + Barts" pattern). We conducted semi-structured interviews with seven PCPs for thematic abstraction. In sixty neonates with presumed Hb Barts on initial NBS who had genetic testing, three (5%) did not have alpha-thalassemia. The remaining 57 (95%) had an alpha-thalassemia trait genotype. Non-deletion alpha-thalassemia occurred in 5%. Eight (13%) had genotypes that substantially altered genetic counseling for the individual and family members. Race and ethnicity were poor surrogates for genotype. PCPs expressed a willingness to participate in NBS follow up but had little specific knowledge about alpha-thalassemia. The addition of genetic testing for likely alpha-thalassemia trait to NBS had very high clinical utility, supporting its use in standard clinical care. Whenever possible, education and genetic counseling should not be provided based on the detection of possible Hb Barts alone without subsequent specific genetic verification. Educational and outreach programs for both PCPs and families about the importance of testing and trait counseling are needed for ongoing improvement.