Prenatal and childhood exposure to phthalate diesters and neurobehavioral development in a 15-year follow-up birth cohort study

Objective: Longitudinal studies on neurobehavioral development in relation to prenatal and postnatal exposure to phthalates in school-age children and adolescents are limited. We investigated the association of prenatal and childhood phthalate exposure with the development of behavioral syndromes in 8–14-year-old children. Method: We recruited 430 pregnant women from 2000 to 2001 and followed their children at the ages of 2, 5, 8, 11, and 14 years, yielding 153 mother–child pairs in total. Urine samples from pregnant women in the third trimester and from children at 2–8 years of age were analyzed for the concentrations of seven urinary phthalate metabolites: monomethyl phthalate, monoethyl phthalate, monobutyl phthalate, monobenzyl phthalate (MBzP), and three di(2-ethylhexyl) phthalate (DEHP) metabolites, namely mono-2-ethylhexyl phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate. Behavioral syndromes in children aged 8–14 years were assessed using the Child Behavior Checklist. We constructed mixed models to examine these associations after adjustments for potential covariates. Results: Maternal urinary MEHP levels were associated with higher scores for internalizing problems (β = 0.028, 95% confidence interval [CI]: 0.0004, 0.055) and externalizing problems (β = 0.040, 95% CI: 0.013, 0.066). Associations of the maternal urinary sum of DEHP metabolite levels with delinquent behavior scores and externalizing problems scores were positive (β = 0.035, 95% CI: 0.013, 0.057 for delinquent behavior; β = 0.026, 95% CI: 0.001, 0.050 for externalizing problems). Furthermore, children's urinary MBzP levels were associated with higher scores for social problems (β = 0.018, 95% CI: 0.001, 0.035). Similar patterns were observed for borderline and clinical ranges. Conclusion: Early-life exposure to phthalates may influence behavioral syndrome development in children. Future studies are needed to replicate these findings, and efforts to reduce exposures to phthalates during critical early life stages may be warranted.