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In utero phthalate exposure has been associated with neurodevelopmental disorders, nevertheless, trimester-specific susceptibility remains understudied. Our aim was to identify susceptible windows to the effects of gestational High-Molecular-Weight Phthalates (HMWP) exposure on 48 months' neurodevelopment. We measured six HMWP metabolites (MEHP, MEHHP, MEOHP, MECPP, MBzP and MCPP) in urine samples collected during each trimester from women in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohort ( n = 218). We assessed children's motor (MS), cognitive (GCI) and memory (MeS) abilities using McCarthy Scales of Children's Abilities (MSCA). We used linear regression models to examine associations between trimester-specific phthalate metabolites and MSCA scores, adjusted for sex, gestational age, breastfeeding, and maternal IQ. Although phthalate concentrations were similar across trimesters, first and second trimester phthalates were inversely associated with MS and GCI, with first trimester associations with MS being the strongest and statistically significant. Stronger associations were seen with MS and GCI among boys compared to girls, however interaction terms were not statistically significant. Our results suggest that early gestation is a sensitive window of exposure to HMWP for neurodevelopment, particularly in boys. Regulations on phthalate content in food as well as pregnancy consumption guidelines are necessary to protect future generations.

Early Gestational Exposure to High-Molecular-Weight Phthalates and Its Association with 48-Month-Old Children’s Motor and Cognitive Scores