Park Seonyoung, Cathey Amber L, Hao Wei, Park Sung Kyun, Mukherjee Bhramar, Montañez Gredia Huerta, Rosario Pabón Zaira Y, Vélez Vega Carmen M, Cordero José F, Alshawabkeh Akram, Watkins Deborah J, Meeker John D
Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Int J Hyg Environ Health. 2025 Jul;268:114599. doi: 10.1016/j.ijheh.2025.114599. Epub 2025 Jun 4.
Phthalates are widely used plasticizers and solvents in a variety of consumer and personal care products, resulting in ubiquitous exposure across the general population. Pregnancy represents a particularly critical window of vulnerability, as prenatal phthalate exposures have been linked to adverse health outcomes, including preterm birth and child developmental problems. While growing evidence highlights potential neurotoxic effects in children, few studies have examined the combined impact of multiple phthalates and newly introduced replacement chemicals. In this study, we included 199 mother-child dyads from the PROTECT birth cohort in Puerto Rico. We assessed prenatal exposure to multiple phthalates and a replacement chemical, di(2-ethylhexyl) terephthalate (DEHTP), by measuring biomarkers in maternal urine samples. Neurodevelopmental outcomes were then evaluated in early childhood (ages 1-3 years) across multiple domains - adaptive, cognitive, communication, motor, and personal-social. We employed a range of mixture modeling approaches-adaptive elastic net (adENET), Bayesian kernel machine regression (BKMR), and quantile g-computation (Q-gcomp). We identified mono(carboxyisononyl) phthalate (MCOP) as a key contributor to poorer neurodevelopmental outcomes and observed an overall adverse trend for the combined mixture. These results provide evidence of additive and mixture effects among multiple phthalates and replacement chemicals, underscoring the need for further research to elucidate the biological mechanisms by which these exposures may collectively influence child neurodevelopment.
邻苯二甲酸盐是广泛应用于各种消费品和个人护理产品中的增塑剂和溶剂，导致普通人群普遍接触。怀孕是一个特别关键的脆弱期，因为产前邻苯二甲酸盐暴露与不良健康后果有关，包括早产和儿童发育问题。虽然越来越多的证据凸显了对儿童潜在的神经毒性影响，但很少有研究考察多种邻苯二甲酸盐和新引入的替代化学品的综合影响。在本研究中，我们纳入了来自波多黎各PROTECT出生队列的199对母婴。我们通过测量母亲尿液样本中的生物标志物，评估了产前对多种邻苯二甲酸盐和一种替代化学品——对苯二甲酸二（2-乙基己基）酯（DEHTP）的暴露情况。然后在幼儿期（1至3岁）多个领域——适应性、认知、沟通、运动和个人社交方面评估神经发育结果。我们采用了一系列混合模型方法——自适应弹性网络（adENET）、贝叶斯核机器回归（BKMR）和分位数g计算（Q-gcomp）。我们确定单（羧基异壬基）邻苯二甲酸酯（MCOP）是导致较差神经发育结果的关键因素，并观察到混合混合物总体上有不良趋势。这些结果提供了多种邻苯二甲酸盐和替代化学品之间存在相加和混合效应的证据，强调需要进一步研究以阐明这些暴露可能共同影响儿童神经发育的生物学机制。
