REVIEW article

Front. Genet.

Sec. RNA

Volume 16 - 2025 | doi: 10.3389/fgene.2025.1628632

MicroRNAs as novel biomarkers for prenatal fetal congenital heart diseasesystematic literature review

Provisionally accepted
Adrianna  KondrackaAdrianna Kondracka1Paulina  Gil-KulikPaulina Gil-Kulik1Magda  Rybak-KrzyszkowskaMagda Rybak-Krzyszkowska2,3Jakub  Marcin StaniczekJakub Marcin Staniczek4Anna  OniszczukAnna Oniszczuk1Bartosz  KondrackiBartosz Kondracki1*
  • 1Medical University of Lublin, Lublin, Poland
  • 2University Hospital Kraków, Kraków, Poland
  • 3University Hospital Krakówtów, Kraków, Poland
  • 4Medical University of Silesia, Katowice, Poland

The final, formatted version of the article will be published soon.

IntroductionCHD accounts for about one-third of all congenital malformations and is the leading cause of infant mortality. Currently, the primary method for diagnosing CHD during pregnancy is fetal echocardiography. Several studies have observed significant differences in the expression levels of specific miRNAs between CHD fetuses and normal fetuses. This systematic review explores the potential of miRNAs as non-invasive biomarkers for the prenatal detection of CHD in fetuses. Material and methods The systematic review followed PRISMA guidelines, conducting a detailed search across PubMed, Scopus, and Web of Science using predefined terms related to microRNAs and congenital heart defects. Inclusion was limited to original, full-text articles in English, while non-English studies, reviews, and inaccessible full texts were excluded. ResultsStudies explored the potential of miRNAs as biomarkers for detecting congenital heart defects (CHD) in fetuses, employing diverse sample types such as maternal serum, umbilical cord blood, and amniotic fluid. Diagnostic methods primarily included fetal echocardiography, complemented by postnatal confirmation through surgery or autopsy. Gestational ages at sample collection ranged predominantly from the second trimester to narrower windows, reflecting methodological variability across studies.The included studies utilized advanced technologies, such as next-generation sequencing and microarrays, for discovery-phase experiments, while validation predominantly employed qRT-PCR techniques. Identified miRNAs showed heterogeneity in expression patterns and diagnostic potential, with several studies reporting high sensitivity, specificity, and AUC values for specific miRNAs like miR-146a-5p and miR-142-5p. While some miRNAs demonstrated exceptional diagnostic accuracy, others were only described in terms of differential expression, highlighting the variability and complexity of miRNA biomarker discovery for CHD.Conslusions The findings of this systematic literature review provide evidence that some miRNAs could serve as non-invasive biomarkers for the early detection of CHD in fetuses. However, each of the reviewed studies identified different miRNAs as potential biomarkers. This variability may stem from differences in experimental methodologies, including approaches to miRNA isolation, quantification techniques, and the types of biological materials analyzed. Such methodological heterogeneity, combined with small sample sizes and the diverse spectrum of CHDs, underscores the need for caution in interpreting these findings.

Keywords: congenital heart defects (CHD), microRNAs (miRNAs), biomarkers, Prenatal Diagnosis, fetal echocardiography, Maternal serum, Amniotic Fluid, umbilical cord blood

Received: 14 May 2025; Accepted: 04 Jul 2025.

Copyright: © 2025 Kondracka, Gil-Kulik, Rybak-Krzyszkowska, Staniczek, Oniszczuk and Kondracki. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Bartosz Kondracki, Medical University of Lublin, Lublin, Poland

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.