AJ Drexel Autism Institute, Drexel University, 3020 Market St, Suite 560, Philadelphia, PA 19104, USA; Department of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, 3215 Market Street, Philadelphia, PA 19104, USA.
AJ Drexel Autism Institute, Drexel University, 3020 Market St, Suite 560, Philadelphia, PA 19104, USA; Center for Metabolic Disease Research, Department of Microbiology and Immunology, Temple University Lewis Katz School of Medicine, 3500 N Broad St. Room 455, Philadelphia, PA 19140, USA.
Sci Total Environ. 2021 Nov 20;796:148898. doi: 10.1016/j.scitotenv.2021.148898. Epub 2021 Jul 7.
Phthalates are chemicals suspected to adversely affect fetal neurodevelopment, but quantifying the fetal exposure is challenging. While prenatal phthalate exposure is commonly quantified in maternal urine, the newborn's meconium may better capture cumulative prenatal exposure. Currently, data on phthalates measured in meconium is sparse. We measured phthalate metabolites in 183 maternal second and 140 third trimester (T2, T3) urine, and in 190 meconium samples collected in an autism enriched-risk pregnancy cohort of 236 mothers. Eleven and eight metabolites were detected in over 90% of urine and meconium samples, respectively. Hydrophilic and hydrophobic metabolites were detected in both biosamples. Most urine phthalate metabolite distributions were similar between T2 and T3. Among metabolites detected in both biosamples, those of di(2-ethylhexyl) phthalate displayed a similar pattern in magnitude across metabolite type. Specifically, T2 creatinine adjusted distribution [median (25%, 75%)] of urine measured mono(2-ethylhexyl-carboxypentyl) (MECPP), mono(2-ethyl-5-hydroxyhexyl) (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) were 18.8(11.9, 31.4), 11.8(7.2, 19.1), and 8.9(6.2, 14.2) ng/mg. In meconium these were 16.6(10.9, 23.7), 2.5(1.5, 3.8), and 1.3(0.8, 2.3) ng/g, respectively. Metabolite-to-metabolite correlations were lower in meconium than urine, but patterns were similar. For example, correlation (95% CI) between mono(2-ethylhexyl) phthalate and MECPP was 0.73 (0.66, 0.78), and between MEOHP and MEHHP was 0.96 (0.95, 0.97) in urine as compared to 0.10 (-0.04, 0.24) and 0.31 (0.18, 0.43) respectively in meconium. Correlations between same metabolites measured in urine and meconium were low and differed by metabolite and trimester. Correlation between MEHHP in urine and meconium, for example, was 0.20 (0.008, 0.37) at T3, but 0.05 (-0.12, 0.21) at T2. Our study provides evidence of general population-level prenatal phthalate exposure in a population at high risk for neurodevelopmental disorders and supports the utility of meconium to measure prenatal phthalate exposure but provides little evidence of correlation with exposure measured in prenatal maternal urine.
邻苯二甲酸酯类是一种被怀疑会对胎儿神经发育产生不利影响的化学物质,但定量评估胎儿的暴露情况具有挑战性。尽管产前邻苯二甲酸酯暴露通常在母体尿液中进行量化,但新生儿的胎粪可能更能反映累积的产前暴露情况。目前,关于胎粪中邻苯二甲酸酯类物质的测量数据还很有限。我们在一个自闭症高风险孕妇队列中,对 236 名母亲的 183 名第二孕期和 140 名第三孕期(T2、T3)尿液以及 190 份胎粪样本中测量了邻苯二甲酸酯代谢物。在尿液和胎粪样本中,分别有 11 种和 8 种代谢物的检出率超过 90%。在这两种生物样本中都检测到了亲水性和疏水性代谢物。在 T2 和 T3 之间,大多数尿液邻苯二甲酸酯代谢物的分布相似。在这两种生物样本中都检测到的代谢物中,二(2-乙基己基)邻苯二甲酸酯(DEHP)的代谢物在同类代谢物中的分布模式相似。具体来说,T2 肌酐调整后的尿液中测量的单(2-乙基己基)羧酸戊基(MECPP)、单(2-乙基-5-羟基己基)(MEHHP)和单(2-乙基-5-氧代己基)邻苯二甲酸酯(MEOHP)的分布[中位数(25%,75%)]为 18.8(11.9,31.4)、11.8(7.2,19.1)和 8.9(6.2,14.2)ng/mg。在胎粪中,这些分别为 16.6(10.9,23.7)、2.5(1.5,3.8)和 1.3(0.8,2.3)ng/g。胎粪中代谢物与代谢物之间的相关性低于尿液,但模式相似。例如,与 MECPP 相比,在尿液中,单(2-乙基己基)邻苯二甲酸酯和 MECPP 的相关性为 0.73(0.66,0.78),MEOHP 和 MEHHP 之间的相关性为 0.96(0.95,0.97),而在胎粪中,两者的相关性分别为 0.10(-0.04,0.24)和 0.31(0.18,0.43)。在尿液和胎粪中测量的相同代谢物之间的相关性较低,且因代谢物和孕期而有所不同。例如,在 T3 时,MEHHP 在尿液和胎粪中的相关性为 0.20(0.008,0.37),但在 T2 时为 0.05(-0.12,0.21)。本研究为高神经发育障碍风险人群的一般人群产前邻苯二甲酸酯暴露情况提供了证据,并支持使用胎粪来测量产前邻苯二甲酸酯暴露情况,但提供的证据很少表明与产前母体尿液中测量的暴露情况存在相关性。