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. CONCLUSION: 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.
