Appropriate Thresholds For Accurate Screening For Beta-Thalassemias In The Newborn Period: Results From A French Center For Newborn Screening

Objectives: Newborn screening (NBS) for beta-thalassemia is based on measuring the expression of the hemoglobin A (HbA) fraction. An absence or very low level of HbA at birth may indicate beta-thalassemia. The difficulty is that the HbA fraction at birth is correlated with gestational age (GA) and highly variable between individuals. We used HbA expressed in multiples of the normal (MoM) to evaluate relevant thresholds for NBS of beta-thalassemia.Methods: The chosen threshold (HbA <= 0.25 MoM) was prospectively applied for 32 months in our regional NBS program for siclde cell disease, for all tests performed, to identify patients at risk of beta-thalassemia. Reliability of this threshold was evaluated at the end of the study.Results: In all, 343,036 newborns were tested, and 84 suspected cases of beta-thalassemia were detected by applying the threshold of HbA <= 0.25 MoM. Among the n=64 cases with confirmatory tests, 14 were confirmed using molecular analysis as beta-thalassemia diseases, 37 were confirmed as beta-thalassemia trait and 13 were false-positive. Determination of the optimum threshold for beta-thalassemia screening showed that HbA <= 0.16 MoM had a sensitivity of 100% and a specificity of 95.3%, whatever the GA.Conclusions: NBS for beta-thalassemia diseases is effective, regardless of the birth term, using the single robust threshold of HbA <= 0.16 MoM. A higher threshold would also allow screening for carriers, which could be interesting when beta-thalassemia constitutes a public health problem.