Parenteral Nutrition as a Source of Xenobiotic Exposure in Preterm Infants in a Single-Center Case Study

In premature infants, successful ex utero maturation depends on endogenous and exogenous stimuli. Chemical insults during this period may impact long-term development. Given immature hepatic biotransformation, parenteral xenobiotic exposure may be of particular toxicological relevance. We conducted a single-center case study to characterize the xenobiotic burden of neonatal parenteral nutrition (PN). A standardized PN regimen for a 28-week, 1000 g reference infant was passed through infusion lines and the flow-through analyzed via a multianalyte exposome LC-MS/MS assay. Eighteen of 221 targeted xenobiotics were detected. Diisononyl phthalate (DINP, 780 ng/mL), bisphenol A (BPA, 250 ng/mL), methylparaben (MP, 74 ng/mL), and 5-hydroxymethyl-2-furanoic acid (HMFA, 43 ng/mL) showed the highest mean concentrations. The estimated daily intake of BPA (9.5 μg/kg bw/d) exceeded calculated and official Health-Based Guidance Values. Consistent with immature detoxification, pharmacokinetic modeling suggested accumulation of DINP, MINP, and free BPA in premature infants. The higher predicted exposure of premature infants to free BPA warrants investigation into 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) formation under potentially saturated Phase II metabolism. An exploratory analysis of plasma data from extremely premature infants indicated PN as a contributory rather than predominant source of intervention-related exposure. These findings represent a relevant clinical reference scenario rather than a population-wide exposure estimate.