Premature infants are at very high risk of suffering from life-long neurological morbidities, including neurosensory impairments, cerebral palsy, cognitive and motor delay, and attention deficit hyperactivity disorder . It is widely accepted, that aberrant inflammation due to post-natal infection can drive the pathogenesis of brain damage , but the xenobiotic influence on early-life immunological development remains poorly explored. Our previously established assay that focused on endogenous and exogenous estrogens was able to assess a comparatively high number of xenobiotics (Preindl et al. 2019 ). However, the selection was based on estrogenic potential and did not include important key toxicants targeting other important modes of action including genotoxicity, carcinogenicity, immunotoxicity, or neurotoxicity. The expanded panel of analytes includes plasticizers, perfluorinated alkylated substances, industrial side products, phyto-and mycotoxins, personal care product ingredients, disinfection byproducts, food processing by-products, and markers of exposure to (cigarette) smoke. We found for instance, that the neonates in our cohort were widely exposed to 2-naphthol, a compound shown to negatively affect the expression of thyroid hormones, thereby potentially impairing early-life brain development . Also, we found perfluorinated compounds to be widely distributed in both premature infant plasma, as well as in breast milk. PFAS were shown to cause persistent neurological defects in adult mice after exposure during the neonatal phase . The possibility of such exposome-scale analysis will enable the assessment of complex co-exposure effects to unravel potential clinical associations between these highly different chemical classes in the future. Besides the broader coverage of analytes and toxicant classes, the presented assay is additionally far more sensitive (on average a factor of ~60 x for the analytes included in Preindl et al. 2019 23 method); the currently most pressing need for generating meaningful data in exposomics. This capacity was clearly demonstrated e.g. by the first-time identification and quantitation of several highly potent xenobiotics of general interest in human breast milk (PhIP, pyrrolizidine-and tropane alkaloids). Importantly, the instrumental platform demonstrated striking linearity, accuracy and precision at the described trace levels that have not been reached before at this scale.