Prenatal exposure to phthalates and neurocognitive development in children at two years of age

Background: Phthalates are a family of endocrine disruptors with short elimination half-lives in the human body. To date, few epidemiological studies have examined repeated measures of maternal urinary phthalates and the combined effects of prenatal exposure to multiple phthalates on children's neurocognitive development. Objectives: We aimed to investigate the association between children's neurocognitive development at 2 years of age and prenatal phthalate exposure, as assessed by repeated measurements during pregnancy, and to further examine the effects of co-exposure to multiple phthalates using cumulative risk assessment. Method: Within a prenatal cohort in Wuhan, China, we measured five high-molecular-weight (HMW) phthalates and three low-molecular-weight (LMW) phthalate metabolites' concentrations in three urine samples collected in the 1st, 2nd, and 3rd trimester of pregnancy from each mother. We assessed neurocognitive development by Bayley Scales of Infant and Toddler Development (BSID) at 2 years of age (n = 476) to obtain the children's mental development index (MDI) and psychomotor development index (PDI). Results: Higher exposure levels to LMW phthalates compared to HMW phthalates were observed in our population. Ln-transformed averaged concentration of mono-n-butyl phthalate (MnBP), a metabolite of the LMW phthalate di-n-butyl phthalate (DnBP) during pregnancy, was associated with decreased PDI scores in all children (beta = -1.90, 95% CI: - 3.43, - 0.37). Similarly, the averaged sum concentration of Sigma dibutyl phthalate (Sigma DBP) was associated with decreased PDI scores in all children (beta = -1.89, 95% CI: -3.63, - 0.15). A negative trend of association between exposure to HMW phthalates and PDI scores was observed in girls, while a positive association was found in boys. In cumulative risk assessment analyses, we consistently observed that the hazard quotient of DnBP (the parent compound of MnBP) was inversely associated with PDI scores in all children, whereas the hazard quotient of di-2-ethylhexyl phthalate (DEHP), an HMW phthalate, was positively associated with PDI scores in boys only. Conclusions: This study is the first to use repeated measurement of maternal urinary phthalates in all three trimesters to assess prenatal exposure in relation to children's neurodevelopment. Our study suggested a negative association between prenatal exposure to MnBP and children's psychomotor development, and potentially sex-specific associations between HMW phthalates and neurocognitive development among boys and girls. These findings warrant further confirmation.