Understanding the impact of in utero exposure to COVID-19 on child neurodevelopment

Historically, it is well documented that infections during pregnancy increase the risk for atypical neurodevelopment in offspring such as intellectual disability, cerebral palsy, autism and schizophrenia. This has been noted in large epidemiological studies following influenza and measles epidemics, with varying degrees of severity depending on the pathogen and the gestation at the time of exposure to the infection. A plausible but unknown prospect are severe long-term neurodevelopmental impacts following in utero exposure to SARS-CoV-2. This highly concerning prospect must be tested to establish the absolute risk and enable early intervention. Transplacental or vertical transmission of SARS-CoV-2 has been reported. Several case reports have confirmed the presence of SARS-CoV-2 in the amniotic fluid and umbilical cord blood, although this appears to be rare. Limited case studies also report elevated anti-SARS-CoV-2 IgM and IgG antibodies and positive nasopharyngeal swab tests in neonates born to SARS-CoV-2 infected mothers. However, while vertical transmission is rare, of considerable concern is the maternal immune response to SARS-CoV-2 and the so called ‘cytokine storm’ that is a common occurrence following infection. Concern over this immune response is borne from previous ecological studies, birth cohort studies and animal models that have established key links between the activation of pro-inflammatory pathways in the mother with adverse neurodevelopment outcomes in the infant. To this end, we have established a large-scale, multi-site international initiative to monitor the long-term neurodevelopmental outcomes of infants exposed to SARS-CoV-2 in utero. The aim of the study is to assess the neurodevelopmental outcomes for children exposed to SARS-CoV-2 in utero. We hypothesise that children of mothers who contracted SARS-CoV-2 infection during pregnancy will show a heightened risk for future neurodevelopmental disorders.