Prenatal phthalate exposure, oxidative stress-related genetic vulnerability and early life neurodevelopment: A birth cohort study

the BIS Investigator Group

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Abstract

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 languageEnglish
Pages (from-to)20-28
Number of pages9
JournalNeurotoxicology
Volume80
Early online date30 May 2020
DOIs
Publication statusPublished - Sept 2020

Funding

We thank the BIS participants for the generous contribution they have made to this project. We also thank current and past staff for their efforts in recruiting and maintaining the cohort and in obtaining and processing the data and biospecimens. The establishment work and infrastructure for the BIS was provided by the Murdoch Children’s Research Institute, Deakin University and Barwon Health. Subsequent funding was secured from the National Health and Medical Research Council of Australia, The Shepherd Foundation, The Jack Brockhoff Foundation, the Scobie Trust, the Shane O’Brien Memorial Asthma Foundation, the Our Women’s Our Children’s Fund Raising Committee Barwon Health, the Rotary Club of Geelong, the Ilhan Food Allergy Foundation, GMHBA Ltd, The Gandel Foundation, The Percy Baxter Charitable Trust, Perpetual Trustees and the Gwenyth Raymond Trust. Vanguard Investments Australia Ltd provided funding for analysis of plasticisers in biospecimens. In-kind support was provided by the Cotton on Foundation and CreativeForce. Research at Murdoch Children’s Research Institute is supported by the Victorian Government's Operational Infrastructure Support Program. A-L. Ponsonby, P. Vuillermin, D. Burgner, V. Anderson and P. Sly receive NHMRC fellowship support. C. Symeonides was supported by a NHMRC PhD scholarship . The BIS Investigator Group includes John Carlin, Mimi Tang and Len Harrison.

FundersFunder number
Barwon Health
Cotton on Foundation
GMHBA Ltd
Our Women's Our Children's Fund Raising Committee Barwon Health
Our Women’s Our Children’s Fund Raising Committee Barwon Health
Percy Baxter Charitable Trust
Rotary Club of Geelong
Scobie Trust
Shane O'Brien Memorial Asthma Foundation
Shane O’Brien Memorial Asthma Foundation
Shepherd Foundation
Rotary Club of Eureka
Jack Brockhoff Foundation
Murdoch Children's Research Institute
National Health and Medical Research Council
Deakin University
Ilhan Food Allergy Foundation
State Government of Victoria
Bank for International Settlements
Percy Baxter Charitable Trust
Shepherd Foundation

    Keywords

    • Autism spectrum disorder
    • Cognition
    • Genetic score
    • Oxidative stress
    • Phthalates
    • Pregnancy

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