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Maternal plasma miRNAs as potential biomarkers for detecting risk of small-for-gestational-age births.

ABSTRACT: Background: Small-for-gestational-age fetuses (SGA) (birthweight <10th centile) are at high risk for stillbirth or long-term adverse outcomes. Here, we investigate the ability of circulating maternal plasma miRNAs to determine the risk of SGA births.

Methods: Maternal plasma samples from 29 women of whom 16 subsequently delivered normally grown babies and 13 delivered SGA (birthweight <5th centile) were selected from a total of 511 women recruited to form a discovery cohort in which expression data for a total of 800 miRNAs was determined using the Nanostring nCounter miRNA assay. Validation by RT-qPCR was performed in an independent cohort.

Findings: Partial least-squares discriminant analysis (PLS-DA) of the Nanostring nCounter miRNA assay initially identified seven miRNAs at 12-14⁺⁶ weeks gestation, which discriminated between SGA cases and controls. Four of these were technically validated by RT-qPCR. Differential expression of two miRNA markers; hsa-miR-374a-5p (p = 0•0176) and hsa-let-7d-5p (p = 0•0036), were validated in an independent population of 95 women (SGA n = 12, Control n = 83). In the validation cohort, which was enriched for SGA cases, the ROC AUCs were 0•71 for hsa-miR-374a-5p, and 0•74 for hsa-let-7d-5p, and 0•77 for the two combined.

Interpretation: Whilst larger population-wide studies are required to validate their performance, these findings highlight the potential of circulating miRNAs to act as biomarkers for early prediction of SGA births.

Funding: This work was supported by Genesis Research Trust, March of Dimes, and the National Institute for Health Research Biomedical Research Centre (NIHR BRC) based at Imperial Healthcare NHS Trust and Imperial College London.

SUBMITTER: Kim SH

PROVIDER: S-EPMC7708817 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Maternal plasma miRNAs as potential biomarkers for detecting risk of small-for-gestational-age births.

Kim Sung Hye SH MacIntyre David A DA Binkhamis Reem R Cook Joanna J Sykes Lynne L Bennett Phillip R PR Terzidou Vasso V

EBioMedicine 20201128

<h4>Background</h4>Small-for-gestational-age fetuses (SGA) (birthweight <10th centile) are at high risk for stillbirth or long-term adverse outcomes. Here, we investigate the ability of circulating maternal plasma miRNAs to determine the risk of SGA births.<h4>Methods</h4>Maternal plasma samples from 29 women of whom 16 subsequently delivered normally grown babies and 13 delivered SGA (birthweight <5th centile) were selected from a total of 511 women recruited to form a discovery cohort in which ...[more]

PMID: 33260001

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Project description:BackgroundIreland introduced a comprehensive workplace smoke-free legislation in March, 2004. Smoking-related adverse birth outcomes have both health care and societal cost implications. The main aim of this study was to determine the impact of the Irish smoke-free legislation on small-for-gestationa- age (SGA) births.Methods and findingsWe developed a population-based birthweight (BW) percentile curve based on a recent study to compute SGA (BW <5(th) percentile) and very SGA (vSGA - BW<3(rd) percentile) for each gestational week. Monthly births born between January 1999 and December 2008 were analyzed linking with monthly maternal smoking rates from a large referral maternity university hospital. We ran individual control and CUSUM charts, with bootstrap simulations, to pinpoint the breakpoint for the impact of ban implementation ( = April 2004). Monthly SGA rates (%) before and after April 2004 was considered pre and post ban period births, respectively. Autocorrelation was tested using Durbin Watson (DW) statistic. Mixed models using a random intercept and a fixed effect were employed using SAS (v 9.2). A total of 588,997 singleton live-births born between January 1999 and December 2008 were analyzed. vSGA and SGA monthly rates declined from an average of 4.7% to 4.3% and from 6.9% to 6.6% before and after April 2004, respectively. No auto-correlation was detected (DW = ~2). Adjusted mixed models indicated a significant decline in both vSGA and SGA rates immediately after the ban [(-5.3%; 95% CI -5.43% to -5.17%, p<0.0001) and (-0.45%; 95% CI: -0.7% to -0.19%, p<0.0007)], respectively. Significant gradual effects continued post the ban periods for vSGA and SGA rates, namely, -0.6% (p<0.0001) and -0.02% (p<0.0001), respectively.ConclusionsA significant reduction in small-for-gestational birth rates both immediately and sustained over the post-ban period, reinforces the mounting evidence of the positive health effect of a successful comprehensive smoke-free legislation in a vulnerable population group as pregnant women.

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Dataset Information

Maternal plasma miRNAs as potential biomarkers for detecting risk of small-for-gestational-age births.

Publications

Maternal plasma miRNAs as potential biomarkers for detecting risk of small-for-gestational-age births.

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