Journal
NEUROTOXICOLOGY
Volume 80, Issue -, Pages 20-28Publisher
ELSEVIER
DOI: 10.1016/j.neuro.2020.05.006
Keywords
Pregnancy; Phthalates; Oxidative stress; Genetic score; Cognition; Autism spectrum disorder
Categories
Funding
- National Health and Medical Research Council of Australia
- Shepherd Foundation
- Jack Brockhoff Foundation
- Scobie Trust
- Shane O'Brien Memorial Asthma Foundation
- Our Women's Our Children's Fund Raising Committee Barwon Health
- Rotary Club of Geelong
- Ilhan Food Allergy Foundation
- GMHBA Ltd
- Gandel Foundation
- Percy Baxter Charitable Trust
- Gwenyth Raymond Trust
- Vanguard Investments Australia Ltd
- Victorian Government's Operational Infrastructure Support Program
- NHMRC
- Perpetual Trustees
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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.
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