Phthalate exposure and neurodevelopment: A systematic review and meta-analysis of human epidemiological evidence

Abstract

Objective: We performed a systematic review of the epidemiology literature to identify the neurodevelopmental effects associated with phthalate exposure. Data sources and study eligibility criteria: Six phthalates were included in the review: di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), dibutyl phthalate (DBP), diisobutyl phthalate (DIBP), butyl benzyl phthalate (BBP), and diethyl phthalate (DEP). The initial literature search (of PubMed, Web of Science, and Toxline) included all studies of neurodevelopmental effects in humans, and outcomes were selected for full systematic review based on data availability. Study evaluation and synthesis methods: Studies of neurodevelopmental effects were evaluated using criteria defined a priori for risk of bias and sensitivity by two reviewers using a domain-based approach. Evidence was synthesized by outcome and phthalate and strength of evidence was summarized using a structured framework. For studies of cognition and motor effects in children ≤4 years old, a random effects meta-analysis was performed. Results: The primary outcomes reviewed here are (number of studies in parentheses): cognition (14), motor effects (9), behavior, including attention deficit hyperactivity disorder (20), infant behavior (3), and social behavior, including autism spectrum disorder (7). For each phthalate/outcome combination, there was slight or indeterminate evidence of an association, with the exception of motor effects for BBP, which had moderate evidence. Conclusions and implications of key findings: Overall, there is not a clear pattern of association between prenatal phthalate exposures and neurodevelopment. There are several possible reasons for the observed null associations related to exposure misclassification, periods of heightened susceptibility, sex-specific effects, and the effects of phthalate mixtures. Until these limitations are adequately addressed in the epidemiology literature, these findings should not be interpreted as evidence that there are no neurodevelopmental effects of phthalate exposure. The views expressed are those of the authors and do not necessarily represent the views or policies of the U.S. EPA.

Phthalate and Bisphenol Exposure during Pregnancy and Offspring Nonverbal IQ

“…2012 ; Radke et al. 2018 , 2020 ). Gonadal hormones are important for sex-specific brain development, and they also play a crucial role in adolescent brain remodeling ( Cohen-Bendahan et al.…”

An Actual Natural Setting Improves Mood Better Than Its Virtual Counterpart: A Meta-Analysis of Experimental Data

“…We then followed the methods from another meta-analysis on the effects of environmental exposure on human health to select which health/well-being outcome measure(s) to analyze (Radke et al, 2020 ). For selection, an outcome should show sensitivity to short-term exposure to natural settings that over time could cumulatively affect health in lasting ways.…”

“…After bias evaluation, the quality of evidence across studies was synthesized to determine the strength of evidence for mood differences between actual and simulated natural settings. We employed a method that was adapted to the framework developed by Radke et al ( 2020 ), which in turn was informed by the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach (Balshem et al, 2011 ). Radke et al ( 2020 ) examined six attributes of associations between environmental exposure data and health outcomes that could be used to support causation: consistency, exposure–response relationships, strength of association, temporal relationship, biological plausibility, and coherence.…”

“…We employed a method that was adapted to the framework developed by Radke et al ( 2020 ), which in turn was informed by the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach (Balshem et al, 2011 ). Radke et al ( 2020 ) examined six attributes of associations between environmental exposure data and health outcomes that could be used to support causation: consistency, exposure–response relationships, strength of association, temporal relationship, biological plausibility, and coherence. Here, we considered only experimental studies with pretest–posttest designs and, therefore, selected only those additional attributes relevant to the current meta-analysis: consistency (similarity of results across studies) and strength of association (effect magnitude and precision of reported results).…”

Critical Review on the Presence of Phthalates in Food and Evidence of Their Biological Impact

“…Although very few studies have been carried out on their neurotoxic effects, phthalates putatively affect the onset of several neurological disorders [ 130 ].…”