Neonatal Intensive Care Unit, Antwerp University Hospital, Edegem, Belgium; Laboratory for Experimental Medicine and Paediatrics, University of Antwerp, Wilrijk, Belgium.
Toxicological Centre, University of Antwerp, Wilrijk, Belgium.
Environ Int. 2024 Apr;186:108605. doi: 10.1016/j.envint.2024.108605. Epub 2024 Mar 28.
Due to endocrine disrupting effects, di-(2-ethylhexyl) phthalate (DEHP), a plasticizer used to soften plastic medical devices, was restricted in the EU Medical Devices Regulation (EU MDR 2017/745) and gradually replaced by alternative plasticizers. Neonates hospitalized in the neonatal intensive care unit (NICU) are vulnerable to toxic effects of plasticizers. From June 2020 to August 2022, urine samples (n = 1070) were repeatedly collected from premature neonates (n = 132, 4-10 samples per patient) born at <31 weeks gestational age and/or <1500 g birth weight in the Antwerp University Hospital, Belgium. Term control neonates (n = 21, 1 sample per patient) were included from the maternity ward. Phthalate and alternative plasticizers' metabolites were analyzed using liquid-chromatography coupled to tandem mass spectrometry. Phthalate metabolites were detected in almost all urine samples. Metabolites of alternative plasticizers, di-(2-ethylhexyl)-adipate (DEHA), di-(2-ethylhexyl)-terephthalate (DEHT) and cyclohexane-1,2-dicarboxylic-di-isononyl-ester (DINCH), had detection frequencies ranging 30-95 %. Urinary phthalate metabolite concentrations were significantly higher in premature compared to control neonates (p = 0.023). NICU exposure to respiratory support devices and blood products showed increased phthalate metabolite concentrations (p < 0.001). Phthalate exposure increased from birth until four weeks postnatally. The estimated phthalate intake exceeded animal-derived no-effect-levels (DNEL) in 10 % of samples, with maximum values reaching 24 times the DNEL. 29 % of premature neonates had at least once an estimated phthalate intake above the DNEL. Preterm neonates are still exposed to phthalates during NICU stay, despite the EU Medical Devices Regulation. NICU exposure to alternative plasticizers is increasing, though currently not regulated, with insufficient knowledge on their hazard profile.
由于内分泌干扰作用，邻苯二甲酸二（2-乙基己基）酯（DEHP），一种用于软化塑料医疗器械的增塑剂，在欧盟医疗器械法规（EU MDR 2017/745）中受到限制，并逐渐被替代增塑剂所取代。在新生儿重症监护病房（NICU）住院的新生儿易受到增塑剂的毒性影响。从 2020 年 6 月到 2022 年 8 月，比利时安特卫普大学医院对出生时胎龄<31 周和/或出生体重<1500g 的早产儿（n=132，每位患者 4-10 个样本）反复采集尿液样本（n=1070）。从产科病房纳入足月对照新生儿（n=21，每位患者 1 个样本）。使用液相色谱-串联质谱法分析邻苯二甲酸酯和替代增塑剂代谢物。几乎所有的尿液样本中都检测到了邻苯二甲酸酯代谢物。替代增塑剂二（2-乙基己基）己二酸酯（DEHA）、二（2-乙基己基）对苯二甲酸酯（DEHT）和环己烷-1,2-二羧酸二异壬酯（DINCH）的代谢物检测频率为 30-95%。与对照新生儿相比，早产儿的尿液中邻苯二甲酸酯代谢物浓度明显更高（p=0.023）。NICU 接触呼吸支持设备和血液制品会导致邻苯二甲酸酯代谢物浓度增加（p<0.001）。从出生到生后 4 周，邻苯二甲酸暴露量逐渐增加。在 10%的样本中，估计的邻苯二甲酸摄入量超过了动物源性无效应水平（DNEL），最高值达到了 DNEL 的 24 倍。10%的早产儿至少有一次估计的邻苯二甲酸摄入量超过了 DNEL。尽管欧盟医疗器械法规已经生效，但 NICU 期间早产儿仍会接触到邻苯二甲酸。替代增塑剂在 NICU 中的暴露量正在增加，尽管目前不受监管，但对其危害特征的了解还不够充分。
