From Prenatal to Preimplantation Genetic Diagnosis of β-Thalassemia. Prevention Model in 8748 Cases: 40 Years of Single Center Experience

Abstract

The incidence of β-thalassemia in Sardinia is high and β-39 is the most common mutation. The prevention campaign started in 1977 and was performed in a single center (Microcitemico Hospital, Cagliari, Sardinia, Italy). It was based on educational programs, population screening by hematological and molecular identification of the carriers. Prenatal and pre-implantation diagnosis was offered to couples at risk. 8564 fetal diagnosis procedures using different invasive approaches and analysis techniques were performed in the last 40 years. Trans-abdominal chorionic villous sampling was preferred due to lower complication risks and early diagnosis. Chorionic villous DNA was analyzed by PCR technique. 2138 fetuses affected by β-thalassemia were diagnosed. Women opted for termination of the pregnancy (TOP) in 98.2% of these cases. Pre-implantation genetic diagnosis (PGD) was proposed to couples at risk to avoid TOP. A total of 184 PGD were performed. Initially, the procedure was exclusively offered to infertile couples, according to the law in force. The success rate of pregnancies increased from 11.1% to 30.8% when, crucial law changes were enacted, and PGD was offered to fertile women as well. Forty years of β-thalassemia prevention programs in Sardinia have demonstrated the important decrease of this severe genetic disorder.

Changing patterns in the epidemiology of β‐thalassemia

“…59,60 Free voluntary carrier screening as well as prenatal and preimplantation genetic diagnostics are available nationwide. 57,60 Increasing awareness among the general population, leading to acceptance of screening, has been a major success factor of the Italian prevention program. 32,60 In a report covering 40 years of experience with a screening program in Sardinia, the main causes of affected births (3-5 annually in recent years) were false paternity and decline of prenatal screening and pregnancy termination.…”

“…57,60 Increasing awareness among the general population, leading to acceptance of screening, has been a major success factor of the Italian prevention program. 32,60 In a report covering 40 years of experience with a screening program in Sardinia, the main causes of affected births (3-5 annually in recent years) were false paternity and decline of prenatal screening and pregnancy termination. 59,60 In Sicily, an 85% decrease in the in- counseling, and prenatal diagnosis.…”

Use of an automated pyrosequencing technique for confirmation of Sickle Cell Disease

“…It is believed that codon 39 (C> T) is of Roman origin, and has a high prevalence in Sardinia, mainland Italy, Spain, Portugal and Tunisia (19). Different studies also found this mutation to be frequent in Venezuela (18), Northern Greece (20), Syria (21), and confirmed it in Tunisia (22) and Italy (23).…”

Achieving the targets of sustainable development goals (2030 agenda) for congenital disorders in Asia: Bottlenecks and interventions

“…The prevention and control of thalassemias in any national program require a planned program and consultations with all the major stakeholders to establish the various components needed to ensure its success. The program must include an education component for the professionals and public, optimal treatment of the affected patient including safe blood transfusion and iron chelation therapy, cascade screening of the family and population‐wide screening, a registry to provide epidemiological data and a preventive program that may include genetic counseling, prenatal diagnosis and preimplantation genetic diagnosis (Monni, Peddes, Iuculano, & Ibba, ). This holistic approach is cost‐effective and had proven to be successful in reducing the frequency of thalassaemia in many countries such as Cyprus and Greece (Kyrri et al, ; Ladis, Karagiorga‐Lagana, Tsatra, & Chouliaras, ).…”