Maternal plasma miRNAs as biomarkers during mid-pregnancy to predict later spontaneous preterm birth: a pilot study

Clint Gray,Rennae S Taylor,Lesley M Mccowan,Rachna Patel,Mark H Vickers

doi:10.1038/s41598-017-00713-8

Clint Gray, Rennae S Taylor + Show 3 more

Open Access

https://doi.org/10.1038/s41598-017-00713-8

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Journal: Scientific Reports	Publication Date: Apr 11, 2017
Citations: 50	License type: open-access

Affiliation: University of Auckland

Abstract

More than 10% of babies are born too early resulting in over 15 million preterm births and more than one million new-born deaths globally. Although women with a previous spontaneous preterm birth (SPTB) are considered at high risk for recurrence, the majority occur in women without prior history. Prediction of SPTB risk allows for improved care and potential for targeting novel and existing therapeutics to prevent SPTB, which may result in improved outcomes for infant and mother. In this pilot study, a miRNA array was used to analyse plasma from healthy women in their first pregnancy at 20 weeks of gestation who then went on to deliver either at term or experience SPTB at 28–32 weeks. We identified specific miRNA expression profiles that differentiated between those mothers who delivered at term or delivered following SPTB. miR302b, miR1253 and a clustering of miR548 miRNAs were underexpressed in SPTB cases compared to term controls. Conversely, miR223 was elevated in mothers that later experienced a SPTB. The circulating miRNAs identified in the present study may therefore be attractive candidates as non-invasive biomarkers for the early prediction of SPTB. Further larger studies are now warranted to investigate the potential clinical utility of these markers.

Highlights

Preterm birth and its complications are estimated to be responsible for 35% of the world’s 3.1 million annual neonatal deaths, and is the second most common cause of death globally after pneumonia in children under 51
Identification of endogenous miRNAs from human maternal plasma. miRNA expression profiles were analysed in maternal plasma samples from 24 healthy pregnancies at 20 weeks of gestation of which, 12 went on to deliver at term and 12 had a SPBT (28–32 weeks)
In the current study we have identified distinct miRNAs measured in maternal plasma samples at 20 weeks’ of gestation that are associated with a later spontaneous preterm birth (SPTB)

Summary

Introduction

Preterm birth and its complications are estimated to be responsible for 35% of the world’s 3.1 million annual neonatal deaths, and is the second most common cause of death globally after pneumonia in children under 51. It has been reported that the levels of specific miRNAs in the human cervix during pregnancy are predictive of gestational age at delivery, and offer potential biomarkers of preterm birth risk[19]. NanoString utilises a hybridization method that directly interrogates target sequences via an amplification-free process and is highly sensitive, even for low-abundance transcripts such as with plasma miRNA. This method avoids potential bias that may be introduced via PCR amplification steps.

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