Early Detection of Preeclampsia Using Circulating Small non-coding RNA

Abstract

Preeclampsia is one of the most dangerous pregnancy complications, and the leading cause of maternal and perinatal mortality and morbidity. Although the clinical symptoms appear late, its origin is early, and hence detection is feasible already at the first trimester. In the current study, we investigated the abundance of circulating small non-coding RNAs in the plasma of pregnant women in their first trimester, seeking transcripts that best separate the preeclampsia samples from those of healthy pregnant women. To this end, we performed small non-coding RNAs sequencing of 75 preeclampsia and control samples, and identified 25 transcripts that were differentially expressed between preeclampsia and the control groups. Furthermore, we utilized those transcripts and created a pipeline for a supervised classification of preeclampsia. Our pipeline generates a logistic regression model using a 5-fold cross validation on numerous random partitions into training and blind test sets. Using this classification procedure, we achieved an average AUC value of 0.86. These findings suggest the predictive value of circulating small non-coding RNA in the first trimester, warranting further examination, and lay the foundation for producing a novel early non-invasive diagnostic tool for preeclampsia, which could reduce the life-threatening risk for both the mother and fetus.

Development of the human placenta

“…Another approach is to screen maternal blood for biomarkers that reflect placental function. These include miRNAs, exosomes, free DNA, proteins and short noncoding RNAs (Barchitta et al, 2017;Gaccioli et al, 2018;Rolnik et al, 2018;Tsang et al, 2017;Yoffe et al, 2018). The benefits of these screening tests in low risk populations are still not obvious, particularly as the only intervention possible at present is early delivery with obvious risk to the neonate; moreover, some reports suggest that these screening tests may actually be harmful (Monier et al, 2015).…”

Salivary uric acid as a predictive test of preeclampsia, pregnancy‐induced hypertension and preterm delivery: A pilot study

“…6 Serum biomarkers, uterine artery Doppler ultrasound and maternal risk have been evaluated as potential predictive tests for PE both individually and in combination but all lack sufficient sensitivity and specificity. [7][8][9][10][11] Though accuracy of the placental growth factor/soluble fms-like tyrosine kinase-1 (PlGF/sFlt-1) test is promising in triage of women at risk of early onset PE in the third trimester, its use as a first and second trimester marker appears limited. 12,13 However, a combination of maternal factors, mean arterial blood pressure, placental growth factor and uterine artery pulsatility index has shown promising results for detecting preterm PE but lacked sufficient detection rates with respect to overall PE.…”

Deep Sequencing Identified Dysregulated Circulating MicroRNAs in Late Onset Preeclampsia

“…In a recent study by Timofeeva et al (2018), miR-423-5 was identified as a candidate biomarker for the early diagnosis of EOPE (19). Yoffe et al (2018) also investigated small non-coding RNAs (ncRNAs), including miRNAs, in the first trimester maternal plasma of 75 PE and control samples and identified 25 transcripts aberrantly expressed between the two groups (20). These transcripts were then used to design a model for the early prediction of PE with an average AUC value of 0.86.…”