Hair as an alternative matrix to assess exposure of premature neonates to phthalate and alternative plasticizers in the neonatal intensive care unit

Due to adverse health effects, di-(2-ethylhexyl) phthalate (DEHP), a plasticizer used to soften plastic medical devices (PMDs), was restricted, and gradually replaced by alternative plasticizers (APs). Up to this date, urine was the sole matrix studied for plasticizer exposure in neonates hospitalized in the neonatal intensive care unit (NICU), a population highly vulnerable to toxic effects of plasticizers. The primary aim of this study was to assess simultaneous measurement of phthalate and AP metabolites in neonatal scalp hair. In addition, we aimed to use this matrix to investigate exposure of premature neonates to plasticizers during their stay in the NICU.Hair samples in this study were collected from premature neonates and their mothers included in a prospective birth cohort study in a tertiary NICU at the Antwerp University Hospital (UZA), Belgium. Samples from pre-mature neonates (n = 45) and their mothers (n = 107) as well as from control neonates (n = 24) and mothers (n = 29) were analyzed using liquid-chromatography coupled to tandem mass spectrometry.This is the first study reporting metabolites of phthalate and alternative plasticizers in neonatal hair samples as biomarkers for exposure to these plasticizers. Results showed that hair sampled from premature neonates after a NICU stay contained significantly higher metabolite concentrations of both phthalates (DEHP, DiBP, and DnBP; 9.0-2500, 9.3-2200, and 24.7-5300 ng/g), and alternative plasticizers (DEHA, DEHT, and TOTM; 38.8-3400, 127.5-5700, and 10.8-8700 ng/g) - when compared to healthy control neonates. Besides, DEHP and DEHT metabolite concentrations were significantly higher than in hair sampled from adult populations. In addition, prolonged NICU exposure to non-invasive respiratory support devices and gastric tubes was correlated with increased concentrations in hair samples, indicating accumulation of plasticizers in this alternative matrix.In conclusion, our data indicate that preterm neonates are still highly exposed to phthalate and alternative plasticizers during NICU stay, despite the EU Medical Devices Regulation.