Antenatal Screening and Diagnosis of B-thalassemia in High-Risk Population of Sardinia

Mini Review

Ann Hematol Oncol. 2022; 9(5): 1410.

Antenatal Screening and Diagnosis of ß-thalassemia in High-Risk Population of Sardinia

Monni G¹*, Ibba RM¹, Murgia F¹, Ventrella A² and Murru S²

¹Department of Obstetrics and Gynaecology, Prenatal and Preimplantation Genetic Diagnosis and Fetal Therapy, Microcitemico Hospital, Italy

²Department of Genetics and Genomics, Microcitemico Hospital, Italy

*Corresponding author: Monni G, Department of Obstetrics and Gynaecology, Prenatal and Preimplantation Genetic Diagnosis and Fetal Therapy, Microcitemico Hospital “A. Cao”, via Edward Jenner SNC, 09121, Cagliari, Italy

Received: September 22, 2022; Accepted: October 26, 2022; Published: November 02, 2022


Sardinia, an Italian island in the Mediterranean sea with a population of 1,7 millions, has one of the highest incidence of β-thalassemia with 10-12% of carriers.

Since 1977 we have been offering a capillary screening program and prenatal diagnosis to couples following non-directive genetic counselling.

Thanks to the implementation of new molecular analysis methods, we shifted from prenatal diagnosis performed in 2nd trimester of pregnancy to 1st trimester. In order to avoid termination of pregnancy in case of affected fetuses following prenatal diagnosis we introduced preimplantation genetic testing, thus increasing notably the acceptance rate of antenatal screening and diagnosis by couples at high risk.

In this paper, we report the continuous experience of our prenatal centre in Sardinia in 9,324 antenatal diagnoses of β-thalassemia, the accuracy and safety related to the prenatal procedures we employed, the termination of pregnancy rate and the couples’ acceptance of the different approaches as well as analyze the screening programs available to the Sardinian population.

Molecular screening by Polymerase Chain Reaction (PCR) based methods, prenatal diagnosis by Chorionic Villous Sampling (CVS) with very low fetal loss rate (0,3%) and Preimplantation Genetic Diagnosis (PGD) were the most common techniques applied in our prenatal centre and they have brought to a drastical reduction of newborns affected by β-thalassemia to only 3-5 per year.

Keywords: Thalassemia; Molecular screening; DNA; Prenatal and preimplantation genetic diagnosis; Termination of pregnancy


Chorionic Villous Sampling (CVS), Quantitative Fluorescent Polymerase Chain Reaction (QF-PCR), Preimplantation Genetic Diagnosis (PGD), Transabdominal CVS (TA-CVS), Termination of Pregnancy (TOP), Prenatal Diagnosis (PD)


β-thalassemia is the most common inherited autosomal recessive disease in the world with more than 200,000 million carriers and 250,000 affected babies are born every year. The disease is widespread mostly in the Mediterranean region, North Africa, Middle East, Far East and East Asia. However, due to the complex migration trends, β-thalassemia is also diffused worldwide [1].

Sardinia, an Italian island in the Mediterranean sea with a population of 1,7 millions is at high risk incidence of β-thalassemia, with 10-12% of carriers which means that nowadays about 1 of 50 couples are at risk of genetic transmission of this disorder. In absence of prevention by antenatal genetic screening and diagnosis and with the progressive denatality in Sardinia, the affected newborns are estimated to be about 60-70 per year [2].

People affected by β-thalassemia are characterized by severe haemolitic anemia, hepatosplenomegaly and characteristic skeletal malformations such as osteoporosis and dysmorphic facies. Without prevention and therapy their survival and life quality is highly compromised and generally difficult.

Affected people necessitate regular blood transfusion and iron chelation. Bone marrow transplantation from an HLA identical sibling is the only possibility to cure the disease with a success rate of 90% [3].

β-thalassemia is characterized by absent to minimal hemoglobin A (0-30%), variable hemoglobin A2 (2-5%), and hemoglobin F (95- 70%). More than 200 different molecular defects have been described and 95% of them cause β-globin gene joint mutations [4].

In this paper we describe the prevention of β-thalassemia performed in our Ob/Gyn Department in Cagliari, Sardinia by antenatal molecular screening, prenatal and preimplantation genetic diagnosis (PGD) in the last 45 years from 1977 to 2022 using different diagnostic approaches.

Identification of Carriers and Molecular Screening

A voluntary β-thalassemia screening program in Sardinia was launched in 1974-75 involving mass media, family doctors, obstetricians, pediatricians, geneticists, midwives and students of all ages in order to inform the whole population on its transmission and prevention and to provide blood testing in order to identify the carriers and the molecular mutations [5].

The most commonly identified point mutation (95,7%) in Sardinia was c.118C>T [4] (Table 1).