Kondracka Adrianna, Gil-Kulik Paulina, Rybak-Krzyszkowska Magda, Staniczek Jakub, Oniszczuk Anna, Kondracki Bartosz
Department of Obstetrics and Pathology of Pregnancy, Medical University of Lublin, Lublin, Poland.
Department of Clinical Genetics, Medical University of Lublin, Lublin, Poland.
Front Genet. 2025 Jul 30;16:1628632. doi: 10.3389/fgene.2025.1628632. eCollection 2025.
CHD 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.
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. Data extraction and quality assessment using the Newcastle Ottawa Scale ensured comprehensive evaluation and minimized bias.
Studies 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 (16-27 weeks) to narrower windows, reflecting methodological variability across studies. The included studies utilized advanced technologies, such as next-generation sequencing (e.g., Illumina HiSeq, NovaSeq) 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.
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. At this stage, it is not feasible to translate these results into clinical practice or establish standardized miRNA-based prenatal screening protocols.
先天性心脏病（CHD）约占所有先天性畸形的三分之一，是婴儿死亡的主要原因。目前，孕期诊断CHD的主要方法是胎儿超声心动图检查。多项研究观察到CHD胎儿与正常胎儿之间特定微小RNA（miRNA）表达水平存在显著差异。本系统评价探讨了miRNA作为胎儿CHD产前检测非侵入性生物标志物的潜力。
本系统评价遵循PRISMA指南，使用与微小RNA和先天性心脏病相关的预定义术语，在PubMed、Scopus和Web of Science上进行详细检索。纳入仅限于英文原创全文文章，排除非英文研究、综述及无法获取的全文。使用纽卡斯尔渥太华量表进行数据提取和质量评估，确保全面评价并最小化偏倚。
研究探讨了miRNA作为检测胎儿先天性心脏病（CHD）生物标志物的潜力，采用了多种样本类型，如母体血清、脐带血和羊水。诊断方法主要包括胎儿超声心动图检查，并通过手术或尸检进行产后确认。样本采集时的孕周主要从孕中期（16 - 27周）到更窄的时间段，反映了各研究方法的差异。纳入的研究在发现阶段实验中使用了先进技术，如下一代测序（如Illumina HiSeq、NovaSeq）和微阵列，而验证主要采用定量逆转录聚合酶链反应（qRT-PCR）技术。鉴定出的miRNA在表达模式和诊断潜力上存在异质性，多项研究报告了特定miRNA（如miR-146a-5p和miR-142-5p）具有高灵敏度、特异性和曲线下面积（AUC）值。虽然一些miRNA显示出卓越的诊断准确性，但其他一些仅在差异表达方面有所描述，凸显了CHD的miRNA生物标志物发现的变异性和复杂性。
本系统文献综述的结果提供了证据，表明一些miRNA可作为胎儿CHD早期检测的非侵入性生物标志物。然而，每项纳入研究都鉴定出不同的miRNA作为潜在生物标志物。这种变异性可能源于实验方法的差异，包括miRNA分离方法、定量技术以及所分析生物材料的类型。这种方法学异质性，再加上样本量小和CHD的多样谱，强调在解释这些结果时需谨慎。现阶段，将这些结果转化为临床实践或建立基于miRNA的标准化产前筛查方案是不可行的。
