Risk of Neurodevelopmental Disorders in Preschool Children Associated with the Longitudinal Trajectory of Phthalates during Pregnancy: Potential Mechanisms Based on Metabonomics of Cord Blood

Phthalate exposure during pregnancy may result in neurotoxicity to offspring, but no studies have investigated the effects of longitudinal phthalate trajectories during pregnancy on children. Therefore, exposure trajectories were constructed by using urine concentrations of phthalates at different times. Similarly, 3220 children were screened for symptoms of autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and emotional and behavioral problems (EBPs) via multiple measures between the ages of 1.5 and 6 years. We also explored potential biological mechanisms through the metabonomics of cord blood. The results showed that high MMP during pregnancy was positively associated with autistic traits in all children (OR: 2.09, 95%CI: 1.10, 4.00) and boys (OR: 2.47, 95%CI: 1.08, 5.63). High LMWP (OR: 3.43, 95%CI: 1.15, 10.20), DEHP (OR: 3.24, 95%CI: 1.08, 9.69), or all phthalates (OR: 4.87, 95%CI: 1.48, 16.05) increased the probability of the occurrence of autistic traits. High MBP exposure in late pregnancy slightly increased the incidence of ADHD (OR: 1.61, 95%CI: 0.91, 2.85). High MBP (OR: 1.42, 95%CI: 1.02, 1.97) exposure increased the incidence of EBPs. Sex-specific associations were also observed. Mechanistically, phthalate exposure interfered with linoleic and arachidonic acid (AA) metabolism. In summary, longitudinal exposure to phthalates during pregnancy may increase the risk of neurodevelopmental disorders (NDDs) in children with sex-specificity. These findings may provide new insights into the underlying mechanisms of phthalates affecting neurodevelopment.