Chemical exposures in utero, child neurodevelopment and epigenetic programming
Toxicants, like lead and plasticisers, are part of our everyday life and ubiquitous in our environment. Many chemicals can interfere with and are toxic to brain development (neurotoxicants), particularly during periods of vulnerability like fetal development. Globally there is a shared need to better understand how environmental chemicals affect brain development and behaviour. This will inform evidence-based global initiatives that promote healthy brain development in future generations.
Research question: ‘What environmental chemical exposures in utero, singly and as mixtures, influence the development of (i) behaviour characteristics of Attention-Deficit/Hyperactivity disorder and autism as well as (ii) other key neurodevelopmental dimensions that can be quantified through direct objective assessments (e.g. executive function, cognition, neurobiological read-outs)?’
- To identify prenatal environmental chemicals, singly and as mixtures, that are associated with (i) behaviours and traits characteristic of ADHD and autism, and (ii) direct objective neurodevelopmental assessments (i.e executive function, cognition, neurobiological read-outs)
- To examine the extent to which identified prenatal environmental chemicals or mixtures (identified in Aim 1) are influencing neurodevelopment through a priori biological pathways (e.g. oxidative stress, dopaminergic metabolism). We will consider:
- modification by genes
- mediation via in utero epigenetic programming.
Exposure to everyday environmental chemicals – e.g. chemicals in plastic products, household chemicals, personal care products etc – during pregnancy may be harmful to brain development. We have reported in the Barwon Infant Study cohort (Australia n=1,074) that the combined effect of an exposure to a mix of plastic chemicals in pregnancy and a child’s genetic predisposition for low antioxidant capacity – approx. 20% of children – was associated with an increased likelihood of Autism Spectrum Disorder (ASD; attributable proportion due to the combination was high at 84%, p<0.0001) and Attention-Deficit/Hyperactivity Disorder (ADHD; attributable proportion 59%, p=0.008).
Recent work also indicates that neurodevelopmental effects may be caused by the silencing of key genes, such as Brain Derived Neurotrophic Factor (BDNF), through gene methylation. Collectively, these findings urgently need to be examined in the context of other common ubiquitous neurotoxic chemicals and with the incorporation of direct objective assessments of neurodevelopment (e.g. executive function, cognition, neurobiological read-outs). We also assess findings in another birth cohort (Avon Longitudinal Study of Parents and Children (ALSPAC) study, UK (n=13,988)) to provide a global assessment of the impacts of chemical exposure on or implicated in the development of neurodevelopmental conditions.
We have an outstanding opportunity to understand this issue in a global context, providing impact for children globally. Through recent international collaborations (such as our work with Canadian APrON cohort and The ENDpoiNTs Project) and continual involvement with World Health Organization Initiatives we have the cohort resources, expertise, and networks to maximise translation on a global scale.
Our focus on chemical exposures in pregnancy is justified as this is a finite interventional window where major translational outcomes can be achieved by updating recommendations against neurotoxic chemicals. Our research has already contributed to updated EU Safety Standards on Bisphenol-A. Given the global mission to minimize adverse impacts of chemicals, we anticipate rapid translation (<5yrs) of evidence-based recommendations to promote healthy brain development in future generations.
Murdoch Children Research Institute (Professor Richard Saffery)
Child Health Research Centre, University of Queensland (Professor Peter D Sly)
Child Health Research Centre, University of Queensland (Dr Dwan Vilcins)