Neuroprogramming of prenatal phthalate exposures on fluid cognition: A latent variable modeling approach to quantify exposure burden and integrate neurobehavioral data

IF 2.8 3区医学 Q3 NEUROSCIENCES

Neurotoxicology and teratology Pub Date : 2026-01-01 Epub Date: 2025-12-04 DOI:10.1016/j.ntt.2025.107575

Jamil M. Lane , Nathan Cohen , Vishal Midya , Cecilia S. Alcala , Shoshannah Eggers , Sandra Martinez-Medina , Damaskini Valvi , Martha M. Téllez-Rojo , Deborah A. Cory-Slechta , Robert O. Wright , Shelley H. Liu

{"title":"Neuroprogramming of prenatal phthalate exposures on fluid cognition: A latent variable modeling approach to quantify exposure burden and integrate neurobehavioral data","authors":"Jamil M. Lane , Nathan Cohen , Vishal Midya , Cecilia S. Alcala , Shoshannah Eggers , Sandra Martinez-Medina , Damaskini Valvi , Martha M. Téllez-Rojo , Deborah A. Cory-Slechta , Robert O. Wright , Shelley H. Liu","doi":"10.1016/j.ntt.2025.107575","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Phthalates are endocrine-disrupting chemicals with neuroactive properties linked to maladaptive neurodevelopment in children. However, few studies have utilized latent variable methodologies to estimate their cumulative impact and assess the complex integration of cognitive processes that characterize fluid cognition—the ability to efficiently process, manipulate, and integrate information to solve reasoning problems.</div></div><div><h3>Objective</h3><div>We investigated the prenatal trimester-specific neuroprogramming effects of the phthalate burden scores on fluid cognition in Mexican children.</div></div><div><h3>Methods</h3><div>Children (<em>n</em> = 626) aged 6–7 years from a prospective pregnancy cohort in Mexico City were administered subtests from the CANTAB, completing the between error, strategy, and mean latency measures intended to evaluate a broad spectrum of cognitive domains representative of fluid cognition. Phthalate metabolites were measured in maternal urine collected at 2nd and 3rd pregnancy trimesters. A CFA validated and quantified two correlated latent phthalate burden scores representing prenatal exposure to low molecular weight (LMW) and high molecular weight (HMW) phthalates. Trimester-specific models using a covariate-adjusted SEM estimated the associations of latent phthalate burden scores with a latent construct of fluid cognition, an integration of working memory, executive function, and attention tasks.</div></div><div><h3>Results</h3><div>In the 3rd trimester, higher LMW phthalate burden was associated with poorer fluid cognition (b = −1.860; [95 % CI = −3.505, −0.215]; <em>p</em> = 0.027), while HMW phthalate burden showed a positive association (b = 1.815; [95 % CI = 0.176, 3.453]; <em>p</em> = 0.030). Conversely, in the 2nd trimester, neither burden levels of LMW (b = −0.508; [95 % CI = −1.639, 0.623]; <em>p</em> = 0.378) nor HMW (b = 0.451; [95 % CI = −0.671, 1.573]; <em>p</em> = 0.431]; <em>p</em> = 0.44) phthalate demonstrated significant associations with fluid cognitive performance.</div></div><div><h3>Conclusion</h3><div>The temporal sensitivity of prenatal phthalate exposures on fluid cognition showed effects in later stages, with higher LMW burden linked to poorer performance and HMW burden showing a positive association. Our findings emphasize latent variable approaches and the need for more research on exposure-driven integrated cognitive programming.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"113 ","pages":"Article 107575"},"PeriodicalIF":2.8000,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurotoxicology and teratology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0892036225001527","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/12/4 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Phthalates are endocrine-disrupting chemicals with neuroactive properties linked to maladaptive neurodevelopment in children. However, few studies have utilized latent variable methodologies to estimate their cumulative impact and assess the complex integration of cognitive processes that characterize fluid cognition—the ability to efficiently process, manipulate, and integrate information to solve reasoning problems.

Objective

We investigated the prenatal trimester-specific neuroprogramming effects of the phthalate burden scores on fluid cognition in Mexican children.

Methods

Children (n = 626) aged 6–7 years from a prospective pregnancy cohort in Mexico City were administered subtests from the CANTAB, completing the between error, strategy, and mean latency measures intended to evaluate a broad spectrum of cognitive domains representative of fluid cognition. Phthalate metabolites were measured in maternal urine collected at 2nd and 3rd pregnancy trimesters. A CFA validated and quantified two correlated latent phthalate burden scores representing prenatal exposure to low molecular weight (LMW) and high molecular weight (HMW) phthalates. Trimester-specific models using a covariate-adjusted SEM estimated the associations of latent phthalate burden scores with a latent construct of fluid cognition, an integration of working memory, executive function, and attention tasks.

Results

In the 3rd trimester, higher LMW phthalate burden was associated with poorer fluid cognition (b = −1.860; [95 % CI = −3.505, −0.215]; p = 0.027), while HMW phthalate burden showed a positive association (b = 1.815; [95 % CI = 0.176, 3.453]; p = 0.030). Conversely, in the 2nd trimester, neither burden levels of LMW (b = −0.508; [95 % CI = −1.639, 0.623]; p = 0.378) nor HMW (b = 0.451; [95 % CI = −0.671, 1.573]; p = 0.431]; p = 0.44) phthalate demonstrated significant associations with fluid cognitive performance.

Conclusion

The temporal sensitivity of prenatal phthalate exposures on fluid cognition showed effects in later stages, with higher LMW burden linked to poorer performance and HMW burden showing a positive association. Our findings emphasize latent variable approaches and the need for more research on exposure-driven integrated cognitive programming.

查看原文本刊更多论文

产前邻苯二甲酸盐暴露对流体认知的神经编程：一种量化暴露负担和整合神经行为数据的潜在变量建模方法

邻苯二甲酸盐是一种干扰内分泌的化学物质，具有神经活性，与儿童神经发育不良有关。然而，很少有研究利用潜在变量方法来估计其累积影响，并评估流体认知特征的认知过程的复杂整合-有效处理，操纵和整合信息以解决推理问题的能力。目的探讨邻苯二甲酸盐负担评分对墨西哥儿童流体认知的产前妊娠特异性神经规划效应。方法对来自墨西哥城的6-7岁的儿童（n = 626）进行CANTAB亚测试，完成误差、策略和平均潜伏期测量，旨在评估流体认知的广泛认知领域。在妊娠第2和第3个月收集的孕妇尿液中测量邻苯二甲酸盐代谢物。CFA验证并量化了两个相关的潜在邻苯二甲酸盐负担评分，代表产前暴露于低分子量（LMW）和高分子量（HMW）邻苯二甲酸盐。使用协变量调整SEM的孕期特异性模型估计潜在邻苯二甲酸盐负担评分与潜在的流体认知结构、工作记忆、执行功能和注意力任务的整合之间的关联。结果妊娠晚期，高LMW邻苯二甲酸盐负荷与较差的流体认知相关（b =−1.860;[95% CI =−3.505,−0.215];p = 0.027），而高HMW邻苯二甲酸盐负荷与较差的流体认知相关（b = 1.815; [95% CI = 0.176, 3.453]; p = 0.030）。相反，在妊娠中期，LMW负荷水平（b = - 0.508; [95% CI = - 1.639, 0.623]; p = 0.378）和HMW负荷水平（b = 0.451; [95% CI = - 0.671, 1.573]; p = 0.431]; p = 0.44）与液体认知能力均无显著相关性。结论产前邻苯二甲酸盐暴露对流体认知的时间敏感性在后期有影响，LMW负荷高与表现差呈正相关，HMW负荷高与表现差呈正相关。我们的研究结果强调了潜在变量方法以及对暴露驱动的综合认知编程进行更多研究的必要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Neurotoxicology and teratology 医学-毒理学

CiteScore

5.60

自引率

10.30%

发文量

审稿时长

58 days

期刊介绍： Neurotoxicology and Teratology provides a forum for publishing new information regarding the effects of chemical and physical agents on the developing, adult or aging nervous system. In this context, the fields of neurotoxicology and teratology include studies of agent-induced alterations of nervous system function, with a focus on behavioral outcomes and their underlying physiological and neurochemical mechanisms. The Journal publishes original, peer-reviewed Research Reports of experimental, clinical, and epidemiological studies that address the neurotoxicity and/or functional teratology of pesticides, solvents, heavy metals, nanomaterials, organometals, industrial compounds, mixtures, drugs of abuse, pharmaceuticals, animal and plant toxins, atmospheric reaction products, and physical agents such as radiation and noise. These reports include traditional mammalian neurotoxicology experiments, human studies, studies using non-mammalian animal models, and mechanistic studies in vivo or in vitro. Special Issues, Reviews, Commentaries, Meeting Reports, and Symposium Papers provide timely updates on areas that have reached a critical point of synthesis, on aspects of a scientific field undergoing rapid change, or on areas that present special methodological or interpretive problems. Theoretical Articles address concepts and potential mechanisms underlying actions of agents of interest in the nervous system. The Journal also publishes Brief Communications that concisely describe a new method, technique, apparatus, or experimental result.