Mid-pregnancy Maternal Blood Nitric Oxide-Related Gene and miRNA Expression are Associated with Preterm Birth

Abstract

Aim: The nitric oxide (NO) pathway modulates inflammation and may influence birth timing. Patients & methods: Case–control analysis of 136 pregnant women with RNA obtained <28 weeks; n = 212 mRNAs and n = 108 miRNAs in the NO pathway were evaluated. NO-pathway mRNA and miRNA transcript counts in women delivering preterm versus at term were compared, miRNA–mRNA expression levels correlated and prediction models generated. Results: Fourteen genes were differentially expressed in women delivering <37 weeks; 13/14 were also differentially expressed in those delivering <34 weeks (q <0.10) versus term births. Multiple miRNA-mRNA pairs were correlated. Models with gene expression better predicted prematurity than models with only clinical or nongenomic predictors. Conclusion: Maternal blood NO pathway-related mRNA and miRNA expression is associated with prematurity.

Graphical abstract

Lay abstract

Aim: We sought to measure whether changes in RNA in mother’s blood in early pregnancy are predictive of early delivery. Patients & methods: This was a study of 136 pregnant women who had their blood drawn before 28 weeks of pregnancy. We measured changes in RNA in genes related to inflammation, and then compared these changes between women who delivered preterm and those who delivered full term. Results: Several genes differed between women who delivered preterm and those who delivered full term. When we combined genetic and clinical information, we were more accurately able to predict which mothers would deliver preterm and which mothers would deliver at full term, compared with using only clinical information. Conclusion: Using both genetic information from mother’s blood in early pregnancy and clinical information might help identify which women will deliver too soon.

Keywords::

• gene expression
• inflammation
• miRNA
• NO pathway
• pregnancy complications
• prematurity prediction
• preterm birth

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2020-0346

Financial & competing interests disclosure

NIH funded by R01-MD011609 and K24-ES031131. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Data sharing statement

Individual de-identified participant data, that underlie the results reported in this article, in addition to the study protocol, will be available.

Data will be available beginning 12 months and ending 36 months following publication. Requests for data will be reviewed by a Data Sharing Review Committee (chaired by TA Manuck) to ensure that the data requests remain consistent with the participant consent forms. Proposals may be submitted up to 36 months following article publication. Proposals should be directed to [email protected]. To gain access, data requestors will need to submit a data use proposal and sign a data access agreement. Authors of secondary analyses using shared data must attest that their use was in accordance with the terms (if any) agreed to upon their receipt. They must also reference the source of the data using its unique, persistent identifier to provide appropriate credit to those who generated it and allow searching for the studies it has supported. Authors of secondary analyses must explain completely how theirs differ from previous analyses. In addition, those who generate and then share clinical trial datasets deserve substantial credit for their efforts. Those using data collected by others should seek collaboration with those who collected the data. As collaboration will not always be possible, practical or desired, the efforts of those who generated the data must be recognized.

Additional information

Funding

National Institutes of Health(NIH) funded by R01-MD011609 and K24-ES031131. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.