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Prenatal phthalate chemicals may have adverse effects on brain development by various mechanisms including oxidant damage. However, birth cohort findings have been conflicting. This study aimed to (i) investigate the interplay between maternal prenatal phthalate levels, infant genetic vulnerability to oxidative stress, and child neurodevelopment and (ii) examine combined putative oxidant exposures. In a population-based birth cohort of 1064 women with prenatal recruitment in Victoria, Australia, maternal urine was collected at 36 weeks of pregnancy and phthalate metabolite concentrations measured. An unweighted genetic score for oxidative stress was made using a candidate gene approach. Cognition was assessed using the BAYLEY-III at two years (n = 678). Parents completed questionnaires for doctor diagnosed autism spectrum disorder (ASD) (1.4 %), ASD traits (4.9 %) and child inattention/hyperactivity (n = 791). Analyses included multiple linear and logistic regression. Higher prenatal phthalate levels and a higher oxidative stress genetic score were each associated with subsequent ASD. Several oxidative stress-related SNPs modified the association between prenatal phthalates and ASD and other outcomes. Consistent patterns were evident across gene score-phthalate combinations for cognition, ASD, ASD traits and inattention/hyperactivity. Other putative oxidant factors such as prenatal smoking further increased risk. Prenatal phthalate levels and infant oxidative stress-related genetic vulnerability are associated with adverse neurodevelopment. Combined exposures are important. Current recommendations and regulation on maternal phthalate exposure during pregnancy require re-evaluation.

Original publication

DOI

10.1016/j.neuro.2020.05.006

Type

Journal article

Journal

Neurotoxicology

Publication Date

09/2020

Volume

80

Pages

20 - 28

Keywords

Autism spectrum disorder, Cognition, Genetic score, Oxidative stress, Phthalates, Pregnancy, Age Factors, Autism Spectrum Disorder, Child Behavior, Child Development, Child, Preschool, Cognition, Environmental Pollutants, Female, Gene Expression Regulation, Developmental, Gene-Environment Interaction, Gestational Age, Humans, Maternal Exposure, Nervous System, Oxidative Stress, Phthalic Acids, Polymorphism, Single Nucleotide, Pregnancy, Prenatal Exposure Delayed Effects, Risk Assessment, Risk Factors, Twins