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.

中文翻译：

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揭示生物标记物和早产途径的代谢组学：系统评价和流行病学观点。

简介大多数已知的早产危险因素是无法改变的，这是婴儿发病和死亡的主要原因。先进的分子技术正越来越多地用于识别对疾病发展和进展很重要的生物标志物和途径。目的我们回顾文献的现状，并从流行病学的角度对其进行评估。方法在2019年1月31日对PubMed，Embase，CINAHL和Cochrane Central进行搜索，以查找1998年后发表的原创文章，这些文章采用了非靶向代谢组学方法来鉴定早产标记物。对合格的手稿进行了同行评审，其中包括来自旨在确定早产机理和预测指标的人体研究的母体组织的非靶向代谢组学分析得出的原始数据。结果2823结果，符合入选条件的文章14篇。在研究设计，结果定义，生物样本类型或包含协变量和混杂因素方面几乎没有一致性，并且在该评价中几乎没有发现与代谢物的一致性关联。结论迄今为止，有关早产儿代谢组学预测因子的研究在方法学和代谢产物鉴定方面均高度异质。迫切需要在定义明确的人群中进行大型研究，以确定可预测早产的生物标志物，并揭示制定干预策略的机制和目标。且在本评价中未发现与代谢物的一致关联。结论迄今为止，有关早产儿代谢组学预测因子的研究在方法学和代谢产物鉴定方面均高度异质。迫切需要在定义明确的人群中进行大型研究，以确定可预测早产的生物标志物，并揭示制定干预策略的机制和目标。且在本评价中几乎没有发现与代谢物的一致关联。结论迄今为止，有关早产儿代谢组学预测因子的研究在方法学和代谢产物鉴定方面均高度异质。迫切需要在定义明确的人群中进行大型研究，以确定可预测早产的生物标志物，并揭示制定干预策略的机制和目标。