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

Edward E. Winger,Percy Pacora,Roberto Romero,Xuhuai Ji,Nardhy Gomez-Lopez,Jane L. Reed,Gijs B. Afink

doi:10.1371/journal.pone.0236805

Abstract

ObjectiveTo predict spontaneous preterm birth among pregnant women in an African American population using first trimester peripheral blood maternal immune cell microRNA.Study designThis 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/m2; 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. MicroRNA Risk Scores were calculated on the training set and area-under-the-curve receiver-operating-characteristic (AUC-ROC) curves were derived from the validation set.ResultsThe 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 (range: 6.6–12.9 weeks). When the validation population was divided by gestational age at the time of venipuncture into early first trimester (mean 8.4 ±1.0 weeks; range 6.6–9.7 weeks) and late first trimester (mean 11.5±0.8 weeks; range 10.0–12.9 weeks), the AUC-ROC scores for early and late first trimester were 0.79 (95% CI: 0.63 to 0.91) and 0.81 (95% CI: 0.66 to 0.92), respectively.ConclusionQuantification of first trimester peripheral blood MicroRNA identifies risk of spontaneous preterm birth in samples obtained early and late first trimester of pregnancy in an African American population.

Highlights

The World Health Organization (WHO) has defined preterm birth as those occurring before 37 weeks of gestation [1]
When the validation population was divided by gestational age at the time of venipuncture into early first trimester and late first trimester, the AUCROC scores for early and late first trimester were 0.79 and 0.81, respectively
Our results indicate that first trimester maternal blood microRNA identifies the risk of spontaneous preterm birth in blood samples drawn at both early and late first trimester time points in an African American population

Summary

Introduction

The World Health Organization (WHO) has defined preterm birth as those occurring before 37 weeks of gestation [1]. Preterm birth is the leading cause of death in children younger than 5 years of age, accounting for approximately 16% of all deaths, and 35% of deaths among newborn babies (2016 figures) [2]. The annual cost of preterm birth in the United States was estimated at $26.2 billion in 2005 and this number is increasing [3, 4]. Late preterm births experienced an increase of 4% from 2014 through 2016 [5]. Laboratory interrogation of urine, cervical mucus, vaginal secretions, serum, plasma and amniotic fluid has been used to supplement clinically defined risk factors to improve prediction of preterm birth. An individual patient data meta-analysis of 4.1 million singleton births in five high-income countries reported that approximately 65% of all preterm births exhibit none of the 21 pre-specified risk factors [6]

Methods

Results

Conclusion