MicroRNAs isolated from peripheral blood in the first trimester predict spontaneous preterm birth

Abstract

Objective To predict spontaneous preterm birth among pregnant women in an African American population using first trimester peripheral blood maternal immune cell microRNA. Study design This was a retrospective nested case-control study in pregnant patients enrolled between March 2006 and October 2016. For initial study inclusion, samples were selected that met the following criteria: 1) singleton pregnancy; 2) maternal body mass index (BMI) <30 kg/m 2 ; 3) blood sample drawn between 6 weeks to 12 weeks 6 days gestation; 4) live born neonate with no detectable birth defects. Using these entry criteria, 486 samples were selected for study inclusion. After sample quality was confirmed, 139 term deliveries (38-42 weeks) and 18 spontaneous preterm deliveries (<35 weeks) were selected for analysis. Samples were divided into training and validation sets. Real time reverse transcription quantitative polymerase chain reaction (rt-qPCR) was performed on each sample for 45 microRNAs. Micro-RNA Risk Scores were calculated on the training set and area-under-the-curve receiveroperating-characteristic (AUC-ROC) curves were derived from the validation set. Results The AUC-ROC for the validation set delivering preterm was 0.80 (95% CI: 0.69 to 0.88; p = 0.0001), sensitivity 0.89, specificity of 0.71 and a mean gestational age of 10.0 ±1.8 weeks

Significance of Sex Differences in ncRNAs Expression and Function in Pregnancy and Related Complications

“…MicroRNAs are single-stranded ncRNAs (~21-24 nt) that regulate gene expression at the post-transcriptional level by silencing specific target RNAs or by targeting regulatory RNAs such as lncRNAs [22]. Each miRNA can target hundreds or thousands of mRNAs, and their deregulation is associated with an increasing number of human diseases [24][25][26], including several pregnancy-associated disorders [14,27] namely, spontaneous preterm birth [28], small-for-gestational-age (SGA) births [29], ectopic pregnancy [30], GDM [31], and PE [32]. PIWI-interacting RNAs (piRNAs) are another class of short ncRNAs (26-31 nt) involved in the differentiation of embryonic stem cells and in early embryonic development.…”

World Prematurity Day: it takes an NIH village to prevent preterm birth and improve treatments for preterm infants

“…The identification of biomarkers using amniotic fluid and maternal blood biomarkers (transcriptomics, proteomics, and metabolomics) to predict preterm delivery is a major focus of the PRB (46). Importantly, a set of microRNAs from peripheral blood from the first trimester can identify patients at risk for spontaneous preterm delivery with a sensitivity of 89% and a specificity of 71% (46).…”

“…The identification of biomarkers using amniotic fluid and maternal blood biomarkers (transcriptomics, proteomics, and metabolomics) to predict preterm delivery is a major focus of the PRB (46). Importantly, a set of microRNAs from peripheral blood from the first trimester can identify patients at risk for spontaneous preterm delivery with a sensitivity of 89% and a specificity of 71% (46). Transcriptomic signatures in amniotic fluid and maternal blood can predict the development of preterm, pre-labor rupture of membranes, as well as impending preterm delivery within 24 hours (70% sensitivity at a 10% false positive rate) (47,48).…”

Preterm birth buccal cell epigenetic biomarkers to facilitate preventative medicine

“…Although many associations between mid-trimester ms-hCG and/or ms-AFP levels and adverse pregnancy outcomes are statistically significant, the sensitivity and positive predictive value are too low for them to be clinically useful as screening tests for preterm birth 3 , 14 . Other proposed biomarkers of PTB risk include selected inflammatory cytokines 15 – 18 , metabolic lipid products 17 , 19 , specific gene mRNA transcripts 20 , 21 , cervicovaginal proteome 22 , and micro-RNA transcripts 20 , 23 , 24 . Urinary oxidative stress metabolites have also been proposed as biomarkers of preterm birth 25 , 26 .…”