To the Editor,
Thalassemias and hemoglobinopathies pose a serious health concern in Turkey. To address this issue, a national hemoglobinopathy prevention program focusing on premarital screening and prenatal diagnosis was initiated in the provinces with high prevalence since 2000s.1 Recently, Yenilmez et al.2 used fetal blood testing as the diagnostic method to report their findings in prenatal diagnosis. They retrospectively evaluated the hematological parameters in 129 fetuses aged 17-25 weeks of gestation with α-thalassemia, β-thalassemia, or a normal genotype. The authors concluded that the hematological data provided valuable information to clinicians about the fetus, helping families make informed decisions during prenatal diagnosis.
Their study was performed between 2010 and 2020. Had fetal blood sampling been the main invasive approach during that period? Otherwise, what proportion did it account for in the total number of prenatal diagnoses? Indeed, cordocentesis used to be the only approach for fetal thalassemia diagnosis, as per our center’s experience, in the 1990s, before the emergence of DNA diagnosis.3 Fetal blood was analyzed using hemoglobin electrophoresis to determine the levels of HbA or Hb Bart’s for the diagnosis β-thalassemia and α-thalassemia, respectively. However, since the 2000s, reliable molecular assays for rapid thalassemia genotyping have been developed and made commercially available. Therefore, cordocentesis has been seldom preferred as a method for the diagnosis of thalassemia. For instance, at our center, out of 1,568 fetal diagnoses for thalassemia performed between 2020 and 2022, only 50 were via cordocentesis (Figure 1). Furthermore, all cordocentesis procedures were conducted in fetuses exhibiting sonographic signs indicative of homozygous α-thalassemia (Bart’s disease). Dündar Yenilmez and Tuli2 performed molecular diagnosis in all fetal blood samples. Given the relatively high procedure-related complications for cordocentesis, it is unclear why these cases were not offered amniocentesis with amplification refractory mutation system and multiplex PCR.
Upon comparison of the hematological parameters among fetuses with different β-thalassemia genotypes, the authors reported a hemoglobin level of 5.8 ± 1.5 g/dl for β0/β0 fetuses compared with the level of 11.7 ± 0.6 g/dl for normal fetuses. Although we have no evidence of hematological parameters for individuals before birth, we believe a β0/β0 fetus would have a comparable hemoglobin value to that of a normal fetus because a fetus with such a low hemoglobin level would have presented with hydropic features at mid gestation.4 Unlike the α globin gene, the β globin gene remains silenced throughout prenatal life. Consequently, defects in the two β genes do not have a hematological effect on fetuses because HbF (α2γ2) constitutes the major hemoglobin during fetal life, which is gradually replaced by adult hemoglobin (HbA, α2β2) during infancy.5 This is supported by the finding that HbF (%) was 80.4 ± 6.1 and 80.6 ± 3.5 in β0/β0 fetuses and normal fetuses, respectively.
Despite our concerns regarding the results of their study, we agree with Dündar Yenilmez and Tuli2 that fetal blood analysis is an option for fetal genetic diagnosis. However, in this molecular era, the emergence of novel, effective laboratory techniques has considerably decreased the need for fetal blood sampling for genetic diagnostic purposes, even during later pregnancy.