Comprehensive Non-Targeted Analysis of the Prenatal Exposome Reveals Significant Differences in Chemical Enrichment Between Maternal and Fetal Samples

The exposome has been recognized as an important dimension in understanding human disease and complementing the genome but remains largely uncharacterized. We analyzed 295 matched maternal and cord blood samples using non-targeted high-resolution mass spectrometry and characterized exposome features. We compared the chemical enrichment of the maternal and cord blood samples using a similarity network analysis and examined the interactions between the exogenous and the endogenous chemical features using a molecular interaction networks approach. We detected over 700 chemical features in the maternal and cord pairs and we found that maternal samples are more similar in terms of chemical enrichment to their corresponding cord samples compared to other maternal samples or other cord samples. We observed significant associations between 3 poly/perfluoroalkyl substances (PFAS) and endogenous fatty acids in both the maternal and cord samples indicating important interactions between PFAS and fatty acid regulating proteins. To our knowledge, this is the first non-targeted analysis study that uses such large cohort to characterize the prenatal exposome.

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A comprehensive non-targeted analysis study of the prenatal exposome

10.26434/chemrxiv.13093457.v2 ◽

2021 ◽

Author(s):

Dimitri Abrahamsson ◽

Aolin Wang ◽

Ting Jiang ◽

Miaomiao Wang ◽

Aditya Siddharth ◽

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Keyword(s):

Mass Spectrometry ◽

Cord Blood ◽

High Resolution Mass Spectrometry ◽

Critical Periods ◽

Chemical Abundance ◽

Blood Samples ◽

Flight Mass Spectrometry ◽

Targeted Analysis ◽

Technological Advances ◽

Negative Electrospray Ionization

Recent technological advances in mass spectrometry have enabled us to screen biological samples for a very broad spectrum of chemical compounds allowing us to more comprehensively characterize the human exposome in critical periods of development. The goal of this study was three-fold: 1) to analyze 590 matched maternal and cord blood samples (total 295 pairs) using non-targeted analysis (NTA); 2) examine the differences in chemical abundance between maternal and cord blood samples; and 3) examine the associations between exogenous chemicals and endogenous metabolites. We analyzed all samples with high-resolution mass spectrometry (HRMS) using liquid chromatography – quadrupole time-of-flight mass spectrometry (LC-QTOF/MS), in both positive and negative electrospray ionization modes (ESI+ and ESI-) and in soft ionization (MS) and fragmentation (MS/MS) modes for prioritized features. We confirmed 19 unique compounds with analytical standards, we tentatively identified 73 compounds with MS/MS spectra matching, and we annotated 98 compounds using an annotation algorithm. We observed 103 significant associations in maternal and 128 in cord samples between compounds annotated as endogenous and compounds annotated as exogenous. An example of these relationships was an association between 3 poly and perfluoroalkyl substances (PFAS) and endogenous fatty acids in both the maternal and cord samples indicating potential interactions between PFAS and fatty acid regulating proteins.

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