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Metabolomics to reveal biomarkers and pathways of preterm birth: a systematic review and epidemiologic perspective

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Abstract

Introduction

Most known risk factors for preterm birth, a leading cause of infant morbidity and mortality, are not modifiable. Advanced molecular techniques are increasingly being applied to identify biomarkers and pathways important in disease development and progression.

Objectives

We review the state of the literature and assess it from an epidemiologic perspective.

Methods

PubMed, Embase, CINAHL, and Cochrane Central were searched on January 31, 2019 for original articles published after 1998 that utilized an untargeted metabolomic approach to identify markers of preterm birth. Eligible manuscripts were peer-reviewed and included original data from untargeted metabolomics analyses of maternal tissue derived from human studies designed to determine mechanisms and predictors of preterm birth.

Results

Of 2823 results, 14 articles met the inclusion requirements. There was little consistency in study design, outcome definition, type of biospecimen, or the inclusion of covariates and confounding factors, and few consistent associations with metabolites were identified in this review.

Conclusion

Studies to date on metabolomic predictors of preterm birth are highly heterogeneous in both methodology and resulting metabolite identification. There is an urgent need for larger studies in well-defined populations, to determine biomarkers predictive of preterm birth, and to reveal mechanisms and targets for development of intervention strategies.

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Data availability

The data reported in this review is freely available through database search using the included search terms. No dataset is available online.

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Acknowledgements

We would like to thank Elaine Hicks, Tulane Science Library Resource Librarian for her help in forming the search terms for this review.

Funding

This work was funded by NICHD Grant R21HD087878 (Harville, PI), NIDDK Grant U24DK097193-01 (Sumner, PI), and NIEHS grant U19 ES019525-01 (Sumner, Co-I).

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Author notes

  1. R. A. Carter and K. Pan are co-first authors.

Authors and Affiliations

  1. Department of Epidemiology, Tulane School of Public Health and Tropical Medicine, 1440 Canal Street, New Orleans, LA, 70112, USA

    R. A. Carter, K. Pan & E. W. Harville

  2. Department of Nutrition, Nutrition Research Institute, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC, 28081, USA

    S. McRitchie & S. Sumner

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  1. R. A. Carter
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  2. K. Pan
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  3. E. W. Harville
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  4. S. McRitchie
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  5. S. Sumner
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Contributions

EM, SM, SS conceived of the concept of the review. KP and RAC conducted the literature search. KP, RAC, and EM analyzed the search results and wrote the paper. RAC, KP, EM, SM, and SS were involved in revision.

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Correspondence to K. Pan.

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Carter, R.A., Pan, K., Harville, E.W. et al. Metabolomics to reveal biomarkers and pathways of preterm birth: a systematic review and epidemiologic perspective. Metabolomics 15, 124 (2019). https://doi.org/10.1007/s11306-019-1587-1

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