Next-generation biomonitoring of the early-life chemical exposome in neonatal and infant development

Exposure to man-made and natural chemicals is a major, yet not sufficiently considered, environmental risk factor in the etiology of chronic diseases. Current human biomonitoring approaches typically measure a limited number of exposures rather than investigating complex mixtures. The latter would be fundamental and necessary for a holistic assessment of chemical exposure in exposome-wide association studies. In this work, an highly-sensitive liquid chromatography-tandem mass spectrometry approach was developed and thoroughly-validated. The assay enables the simultaneous and targeted assessment of more than 80 highly-diverse xenobiotics in the investigated body fluids of urine, serum/plasma, and breast milk; the detection limit for most toxicants are in the pg-ng/mL range. In the plasma of extremely-premature infants (gestational age <28 weeks, birth weight <1 kg) a total of 27 different xenobiotics are identified; including severe contamination with synthetic plasticizers, perfluorinated alkylated substances and parabens. In an independent sample set of breast milk that was longitudinally collected over the first 211 days post-partum, a total of 29 analytes is detected, including the first-ever identification of pyrrolizidine- and tropane alkaloids in this matrix. Based on the generated data, a preliminary estimation of daily toxicant intake via breast milk is conducted. In conclusion, our proof-of-principle experiments show significant early-life co-exposure to multiple toxicants, and demonstrate the method’s applicability in future large-scale exposomics-type cohort studies in vulnerable populations.