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

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.

Keywords: Biomarker; Metabolite; Metabolomics; Preterm birth.

Figure 1

Flowchart outlining the protocol adopted in this systematic review ¹Data not available for extraction is a combination of studies with no individual level measurement of exposure (n=2) or studies with combined outcomes (n=1)