Digital PCR‐based non‐invasive prenatal diagnosis should be considered in the evolving diagnostic pathway for sickle cell disease
We read with great interest the European Hematology Association (EHA) recommendations by de Montalembert et al. on preconceptual and antenatal screening and prenatal diagnosis for hemoglobino-pathies. The manuscript provides a timely and valuable framework for genetic counseling and reproductive decision ‐ making in thalassemia and sickle cell disease, particularly by emphasizing non ‐ directive counseling and the need to adapt diagnostic strategies to local healthcare infrastructures. 1 We would like to comment specifically on Question 4, concerning the laboratory tests that should be used for prenatal diagnosis. The authors appropriately state that invasive prenatal diagnosis based on chorionic villus sampling or amniocentesis remains the most established diagnostic approach, and they also highlight the current limitations of non ‐ invasive prenatal testing (NIPT)/diagnosis for hemoglobinopathies. In particular, they cite previous data showing that the performance of non ‐ invasive approaches for sickle cell disease has not yet reached that of invasive prenatal diagnosis. 1 However, we believe that this section may benefit from a more explicit distinction in light of recent advances in non ‐ invasive prenatal diagnosis (NIPD) based on cell ‐ free fetal DNA and digital polymerase chain reaction (PCR). Our group has recently published a pilot study evaluating third ‐ generation digital PCR for NIPD of sickle cell disease using relative mutation dosage analysis in maternal plasma. In this study, nine pregnant women carrying the HbS heterozygous variant were included. Z ‐ score classification correctly identified the fetal genotype in all conclusive cases, with one inconclusive result, and postnatal confirmation showed 100% concordance