This study was supported in part by the Regione Autonoma della Sardegna (project code CPR-24750).

Objective (95% CI, specificity 97.5% (95% CI, LR+ 34.7 (95% CI,

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.

Background: Beta-thalassemias are blood disorders characterized by poorly understood clinical phenotypes ranging from asymptomatic to severe anemia. Metabolic composition of the human placenta could be affected by the presence of pathological states such as β-thalassemia. The aim of our study was to describe metabolic changes in chorionic villi samples of fetuses affected by β-thalassemia compared to a control group by applying a metabolomics approach. Methods: Chorionic villi samples were differentiated according to the genetic diagnosis of β-thalassemia: control (Group 1, n = 27); heterozygous (Group 2, n = 7); homozygous (Group 3, n = 7). Gas chromatography–mass spectrometry was used to detect the metabolic composition of the samples. Subsequently, multivariate and univariate statistical analysis was performed. The discriminant metabolites were used to identify the altered pathways. Results: Supervised multivariate models were devised to compare the groups. The model resulting from the comparison between Group 1 and Group 3 was the most significant. Discriminant metabolites were identified, and the most altered pathways were as follows: pentose phosphate pathway (PPP), arachidonic acid metabolism, glycolysis, and gluconeogenesis, suggesting the presence of an energetic shift toward the PPP and the presence of oxidative stress in β-thalassemia chorionic villi samples. Conclusions: The metabolomics approach identified a specific metabolic fingerprint in chorionic villi of fetuses affected by β-thalassemia.

No abstract