The association between prenatal exposure to phthalates and cognition and neurobehavior of children-evidence from birth cohorts.

Background: Phthalate have been detected widely in the environment; while several studies have indicated that prenatal phthalate exposure has adverse effects on neurodevelopment, the results were inconsistent.

Objective: We aimed to determine the current research status of the relationship between prenatal exposure to different types of phthalate and cognition and behavioral development in children. We conducted a systematic review to evaluate the current state of knowledge.

Methods: We systematically searched PubMed, Web of Science, and EMBASE electronic databases up to May 2018 with manual searches of the references of retrieved publications and relevant reviews. Only birth cohort studies that reported on the association between phthalate exposure and cognitive or behavioral development were included in this review. We evaluated the risk of bias for each of the included studies using a modified instrument based on the Cochrane Collaboration's "Risk of Bias" tool.

Result: Twenty-six birth cohort studies met our inclusion criteria, nine of which investigated the impact of phthalate exposure during pregnancy on cognition, 13 on neurobehavior, and 4 on both cognition and neurobehavior. However, ten articles reported that the effect of prenatal exposure to phthalates on cognitive development was statistically significant, 15 articles reported that the effect of prenatal exposure to phthalates on neurobehavior was statistically significant. The effect of prenatal phthalate exposure on neurodevelopment differed according to sex, but the results are inconsistent, for instance, among the five studies investigating the association between mental development index (MDI) and Mono-n-butyl phthalate (MnBP), two of them showed a significantly decreasing MDI scores with increasing concentrations of MnBP among girls, but among boys one study showed the inverse association, another showed the positive association.

Conclusion: Di(2-ethylhexyl) phthalate, dibutyl phthalate, butyl-benzyl phthalate and di-ethyl phthalate exposure during pregnancy was associated with lower cognitive scores and worse behavior in offspring, and sex-specific effects on cognitive, psychomotor, and behavioral development were identified, especially the impact of phthalate exposure on neurobehavior in boys.