Abstract
Objectives
Newborn screening (NBS) for β-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 β-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 β-thalassemia.
Methods
The chosen threshold (HbA≤0.25 MoM) was prospectively applied for 32 months in our regional NBS program for sickle cell disease, for all tests performed, to identify patients at risk of β-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 β-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 β-thalassemia diseases, 37 were confirmed as β-thalassemia trait and 13 were false-positive. Determination of the optimum threshold for β-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 β-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 β-thalassemia constitutes a public health problem.
Acknowledgments
The authors would like to thank Paris area CRDN-IDF program staff (Pr Polak M.), the national reference laboratory of Robert-Debré Hospital (Dr Laskri, Dr Nguyen, Ms Khaldi, Ms Espineta and Ms Alais) for their professionalism, and all pediatricians who participated in this study. We would also like to thank David Marsh who provided editorial assistance.
Research funding: None declared.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals who underwent molecular analysis in this study.
Ethical approval: In accordance with current French law, before sampling, healthcare professionals must inform parents about the NBS program. Oral information on the nature of the test, its objectives and the diseases screened (Cytic Fibrosis, Phenylketonuria, Adrenal Hyperplasia Congenital, Hypothyroidism, and for population at risk: Hemoglobinopathies) must be given. A person with parental authority must give consent for the newborn testing. All procedures were performed in accordance with the 1983 and 2008 revisions of the Declaration of Helsinki. This observational study did not need to be reported to the local Institutional Review Board since it did not change the routine testing by laboratory (screening for β-thalassemia syndrome is one of the objective of this program) and it did not change the routine management of patients.
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