Challenges and Developments in Prenatal Diagnosis of Beta-Thalassemia: A Study on Diagnostic Accuracy

Bijan  Keikhaei; Nozar  Kalantarfard; Mohammad Reza  Mahmoudian-Sani

doi:10.18502/ijpho.v15i4.19631

Bijan Keikhaei Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Nozar Kalantarfard Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Mohammad Reza Mahmoudian-Sani Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

DOI: https://doi.org/10.18502/ijpho.v15i4.19631

Keywords: Beta-Thalassemia, Chorionic Villus Sampling, Diagnostic Error, Mutation, Prenatal Diagnosis

Abstract

Background: Beta-thalassemia major is prevalent in areas like Khuzestan, Iran, and causes severe anemia requiring lifelong treatment. Despite successful prevention programs, diagnostic errors in Prenatal Diagnosis (PND) persist, leading to affected births. This study evaluates the accuracy of PND, identifies the causes of errors, and suggests improvements to diagnostic protocols.

Materials and Methods: A retrospective descriptive cross-sectional study (2012–2018) with 202 beta-thalassemia carrier couples from Shafa Hospital, Ahvaz, Iran. Fetal DNA analysis was conducted via Chorionic Villus Sampling (CVS) and amniotic fluid sampling using Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR), Gap Polymerase Chain Reaction (Gap-PCR), and sequencing. Statistical analysis results revealed factors influencing diagnostic errors.

Results: Affected infants were diagnosed with beta-thalassemia major at an average age of five months. The results showed six diagnostic errors (2.14%), primarily associated with point mutations. Errors occurred more frequently in amniotic fluid sampling (4.05%) than in CVS sampling (1.45%). CD 36/37, IVS-II-1, and Fr8–9 were the most common detected mutations.

Conclusion: Improving the accuracy of PND for beta-thalassemia is crucial, particularly in regions with high prevalence, such as Khuzestan, Iran. Although the overall diagnostic error rate was low (2.14%), the consequences of such errors are significant. The diagnostic error can lead to the birth of affected children and an added burden on families and healthcare systems. Most errors were linked to point mutations and were more frequent in amniotic fluid sampling than in CVS. To minimize such diagnostic mistakes, advancements in molecular diagnostic techniques—especially for detecting rare mutations—are necessary.