Neonatal Exposure to Phthalate and Alternative Plasticizers via Enteral Nutrition

In the neonatal intensive care unit (NICU), patients receive their nutrients through plastic medical devices (PMDs), which are a potential source of phthalates and alternative plasticizers (APs). The aim of this study was to investigate the contribution of enteral nutrition (EN) by analyzing which phthalates and/or APs were present in 19 PMDs commonly used for enteral nutrition administration, using LC-MS/MS and GC-MS. Further, we quantified the concentrations of phthalates, APs, and their respective metabolites in 35 human milk samples and 23 formula milk samples. Lastly, to assess leaching during clinical use, ex vivo leaching experiments simulated in vivo neonatal EN administration. Tris(2-ethylhexyl) trimellitate (TOTM) and di(2-ethylhexyl) phthalate (DEHP) were the predominant plasticizers in PMDs used for neonatal EN administration, with a maximum mass concentration of 0.45% for both, present in gastric tubes. In formula milk samples, the phthalates diisobutyl phthalate (DiBP), DEHP, diisononyl phthalate (DINP), and diisodecyl phthalate (DIDP), and APs acetyl tributyl citrate (ATBC), di(2-ethylhexyl) adipate (DEHA), and cyclohexane-1,2-dicarboxylic diisononyl ester (DINCH) were detected. Our experiments indicate that formula milk administration by itself, but not the leaching from plastic tubing used for enteral feeding, could expose premature neonates to a cumulative phthalate exposure of up to three times above the DNEL value set by the European Chemical Agency. The low migration potential of TOTM provides opportunities to reduce the exposure.