Investigating the impact of in utero COVID-19 exposure on neurodevelopment: a translational pipeline of human and preclinical research programs
Infections during pregnancy are well known to increase risk for the offspring to develop a neurodevelopmental disorder later in life. Of imminent concern then is the risk that COVID-19 infection may cause to the unborn foetus. To this end we established a multisite birth cohort study of infants exposed to COVID-19 in utero from Melbourne, Australia, and Londrina, Brazil. Our published data shows poorer neurodevelopmental outcomes at 12 months of age in infants exposed to severe SARS-CoV-2 infection as well as altered DNA methylation of genes associated with synaptic pathways. Unpublished data from the 2-year-old time point shows altered communication and language as well as higher scores on the Autism diagnostic observation scale (ADOS) in infants exposed to SARS-CoV-2 in utero, as well as altered DNA methylation of over 2000 genes across both Melbourne and Londrina sites. Site replication in two distinct populations adds significant weighting to the significance of these findings. These data are now being reverse translated back into both human induced pluripotent stem cell and animal models to understand the brain mechanisms that link SARS-CoV-2 exposure to adverse brain and behaviour function. Preventative as well as restorative treatment targets are being investigated in these preclinical models to ultimately improve outcomes in infants exposed to infections in utero.
Prof. Hill is head of the Behavioural Neuroscience Laboratory, Department of Psychiatry, Monash University. She leads a multi-disciplinary program that spans the translational continuum, combining advanced neuroscience techniques with molecular biology, human clinical genomics and clinical trials. Prof Hill is president of Biological Psychiatry Australia (BPA) and the founder and chair of the Consortium for Preclinical Psychiatric Research (CPPR).
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