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Noninvasive prenatal testing for congenital heart disease - cell-free nucleic acid and protein biomarkers in maternal blood.
Context: Congenital heart disease (CHD) is the most common fetal malformation. Prenatal ultrasonography is routinely applied for the screening of CHD but many factors influence its diagnostic accuracy. The introduction of new biomarkers could facilitate the identification of high-risk pregnancies. Objective: In our review, our aim was to collect expression studies of cell-free nucleic acids and proteins in maternal circulation. Syndromic CHDs which can be detected by noninvasive prenatal testing (NIPT) techniques were also discussed. Methods: PubMed and Web of Science databases were screened for studies where the levels of potential CHD biomarkers were measured in maternal blood samples. Available NIPT tests were collected from the providers' resources. Results: There are nine CHD-associated chromosomal abnormalities, five aneuploidies, and four microdeletions, which are included in NIPT panels. We found eight articles from which five included the analysis of specific cell-free RNA expression and three measurements of protein levels. Conclusions: Most of the common heart-related chromosomal aberrations can be diagnosed by NIPT. Specific cell-free RNAs and circulating proteins seem to be potential biomarkers for fetal CHDs. The application of these new biomarkers could improve the detection rate at early pregnancy, making it possible to provide optimal perinatal and perioperative management.
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