INTRODUCTION: This study aimed to establish efficient, cost-effective, and early predictive models for adverse pregnancy outcomes based on the combinations of a minimum number of miRNA biomarkers, whose altered expression was observed in specific pregnancy-related complications and selected maternal clinical characteristics. METHODS: This retrospective study included singleton pregnancies with gestational hypertension (GH, n = 83), preeclampsia (PE, n = 66), HELLP syndrome (n = 14), fetal growth restriction (FGR, n = 82), small for gestational age (SGA, n = 37), gestational diabetes mellitus (GDM, n = 121), preterm birth in the absence of other complications (n = 106), late miscarriage (n = 34), stillbirth (n = 24), and 80 normal term pregnancies. MiRNA gene expression profiling was performed on the whole peripheral venous blood samples collected between 10 and 13 weeks of gestation using real-time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Most pregnancies with adverse outcomes were identified using the proposed approach (the combinations of selected miRNAs and appropriate maternal clinical characteristics) (GH, 69.88%; PE, 83.33%; HELLP, 92.86%; FGR, 73.17%; SGA, 81.08%; GDM on therapy, 89.47%; and late miscarriage, 84.85%). In the case of stillbirth, no addition of maternal clinical characteristics to the predictive model was necessary because a high detection rate was achieved by a combination of miRNA biomarkers only [91.67% cases at 10.0% false positive rate (FPR)]. CONCLUSION: The proposed models based on the combinations of selected cardiovascular disease-associated miRNAs and maternal clinical variables have a high predictive potential for identifying women at increased risk of adverse pregnancy outcomes; this can be incorporated into routine first-trimester screening programs. Preventive programs can be initiated based on these models to lower cardiovascular risk and prevent the development of metabolic/cardiovascular/cerebrovascular diseases because timely implementation of beneficial lifestyle strategies may reverse the dysregulation of miRNAs maintaining and controlling the cardiovascular system.

Department of Molecular Biology and Cell Pathology 3rd Faculty of Medicine Charles University Prague Czechia

Institute for the Care of the Mother and Child 3rd Faculty of Medicine Charles University Prague Czechia

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