Relationship of Trimester-Specific Gestational Exposure to High Molecular Weight Phthalates with Neurodevelopment at 48 Months and Differences by Sex

摘要

In-utero phthalate exposure has been associated with neurodevelopmental disorders, further modified by child's sex. Pregnant women are ubiquitously exposed to high molecular weight phthalates (HMWP) through diet. Nevertheless, trimester-specific susceptibility to exposure and effect modification by sex remain understudied. Our aim was to identify susceptible windows to the effects of gestational HMWP exposure and effect modification by sex, on 48-months neurodevelopment. We measured six HMWP metabolites (MBzP, MEHP, MEHHP, MEOHP, MECPP 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 measured children's motor (Ml) and cognitive (GCI) abilities using McCarthy Scales of Children's Abilities (MSCA, lower scores indicated poorer performance). We used linear regression models to examine associations between trimester specific phthalate metabolites (individual, IDEHP, IHMWP) and Ml or GCI scores. Phthalates were log-transformed and specific gravity corrected for all analyses. Models were adjusted for sex, gestational age at birth, breastfeeding, and maternal IQ. Effect modification was assessed stratifying by sex. Phthalate concentrations were similar across trimesters. All 1st and 2nd trimester phthalates were negatively associated with Ml and GCI scores, while half of the 3rd trimester phthalates showed positive associations. Associations between 1st trimester phthalates and Ml scores were the strongest and statistically significant (e.g. MECPP β = -2.6, 95% CI (-4.4, -0.8)). For GCI scores, the magnitude of negative associations were similar for the 1st and 2nd trimester phthalates, but not statistically significant. Overall, boys had stronger GCI and Ml negative associations than girls. Our results suggest that HMWP exposure specifically during early pregnancy were strongly associated with poorer motor abilities at 48 months, particularly in boys.