First-Trimester Screening for Miscarriage or Stillbirth—Prediction Model Based on MicroRNA Biomarkers

Abstract

We evaluated the potential of cardiovascular-disease-associated microRNAs to predict in the early stages of gestation (from 10 to 13 gestational weeks) the occurrence of a miscarriage or stillbirth. The gene expressions of 29 microRNAs were studied retrospectively in peripheral venous blood samples derived from singleton Caucasian pregnancies diagnosed with miscarriage (n = 77 cases; early onset, n = 43 cases; late onset, n = 34 cases) or stillbirth (n = 24 cases; early onset, n = 13 cases; late onset, n = 8 cases; term onset, n = 3 cases) and 80 selected gestational-age-matched controls (normal term pregnancies) using real-time RT-PCR. Altered expressions of nine microRNAs (upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-26a-5p, miR-146a-5p, and miR-181a-5p and downregulation of miR-130b-3p, miR-342-3p, and miR-574-3p) were observed in pregnancies with the occurrence of a miscarriage or stillbirth. The screening based on the combination of these nine microRNA biomarkers revealed 99.01% cases at a 10.0% false positive rate (FPR). The predictive model for miscarriage only was based on the altered gene expressions of eight microRNA biomarkers (upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-26a-5p, miR-146a-5p, and miR-181a-5p and downregulation of miR-130b-3p and miR-195-5p). It was able to identify 80.52% cases at a 10.0% FPR. Highly efficient early identification of later occurrences of stillbirth was achieved via the combination of eleven microRNA biomarkers (upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-146a-5p, and miR-181a-5p and downregulation of miR-130b-3p, miR-145-5p, miR-210-3p, miR-342-3p, and miR-574-3p) or, alternatively, by the combination of just two upregulated microRNA biomarkers (miR-1-3p and miR-181a-5p). The predictive power achieved 95.83% cases at a 10.0% FPR and, alternatively, 91.67% cases at a 10.0% FPR. The models based on the combination of selected cardiovascular-disease-associated microRNAs had very high predictive potential for miscarriages or stillbirths and may be implemented in routine first-trimester screening programs.

Value of Non-Coding RNA Expression in Biofluids to Identify Patients at Low Risk of Pathologies Associated with Pregnancy

“…Cui et al reported an overexpression of serum miRNA-371a-5p and down expression of miRNA-206 [40]. Recently, Hromadnikova et al proposed a predictive model for miscarriage based on the blood expression of eight miRNAs (upregulation of miRNA-1-3p, miRNA-16-5p, miRNA-17-5p, miRNA-26a-5p, miRNA-146a-5p, and miRNA-181a-5p and downregulation of miRNA-130b-3p and miRNA-195-5p) identifying patients at risk in 80.52% of cases [41]. All the above studies are summarized in Table 1.…”

“…SerumHromadnikova et al[41] 2023 181 Upregulated: miRNA-1-3p, miRNA-16-5p, miRNA-17-5p, miRNA-26a-5p, miRNA-146a-5p, miRNA-181a-5p Downregulated: miRNA-130b-3p, miRNA-195-5p…”

Trophoblast Cell Function in the Antiphospholipid Syndrome

“…Since increased levels of miR-146a, miR-155 and miR-210 have been found in placentas of aPLnegative RPL [134,[158][159][160] and PE patients [135][136][137]139,[161][162][163] it could be concluded that aPL-induced upregulation of named miRNAs in trophoblast cells is a contributing factor to the development of these obstetric complications in OAPS patients. Moreover, increased levels of miR-146a, miR-155 and miR-210 were found in blood of patients suffering from pregnancy loss and/or PE [140,[164][165][166][167] suggesting the use of these miRNAs as biomarkers for early diagnostics as well as mechanism-based targets of new therapeutics for RPL and PE associated or not with OAPS.…”

Special Issue of Pathogenesis of Pregnancy-Related Complications, 2023

“…Our research group [ 7 ] also introduces a first-trimester predictive model for late miscarriage and stillbirth based on the altered expression of microRNA biomarkers in maternal whole peripheral blood and selected maternal clinical characteristics that represent risk factors for miscarriage and stillbirth.…”