Second Trimester Maternal Serum microRNAs as Biomarkers for Congenital Diaphragmatic Hernia Severity

Introduction Fetoscopic endoluminal tracheal occlusion (FETO) is currently reserved for severe cases of congenital diaphragmatic hernia (CDH); however, prenatal identification of severity remains challenging given the limitations of prognostication with fetal ultrasound and magnetic resonance imaging. microRNAs (miRNAs), which are small noncoding RNAs circulating in serum that freely cross the placenta, may serve as potential biomarkers. Considering the limitations of fetal imaging in prognostication, we aimed to identify miRNA signatures in second trimester maternal serum (2TMS) that distinguish CDH survivors from nonsurvivors, with potential implications for guiding FETO therapy.Methods 2TMS samples from pregnancies complicated by CDH, seen at our fetal care center, were sequenced for miRNAs. Machine-learning random forest analyses were employed to identify miRNA biomarkers distinguishing CDH survivors from nonsurvivors. Differential miRNA expressions were analyzed using Student's t-test.Results miRNA sequencing and random forest analysis demonstrated miR-409-3p, miR-203a-3p, and miR-181a-5p as the top miRNAs distinguishing CDH survivors from nonsurvivors. Receiver operating characteristic curves exhibited an area under the curve of 0.89, indicating high specificity and sensitivity. miR-409-3p and miR-203a-3p were significantly downregulated, while miR-181a-5p was upregulated in survivors compared to nonsurvivors.Conclusions We identified miR-409-3p, miR-203a-3p, and miR-181a-5p as promising prognostic biomarkers in 2TMS for predicting CDH survival. Future validation across multiple institutions are required to utilize such miRNA biomarkers for FETO therapy recommendations.