Mid-Gestation Cytokine Profiles in Mothers of Children Affected by Autism Spectrum Disorder: a Case-Control Study

Abstract Background: Alterations of gestational cytokine profiles have been reported in mothers of autistic children. Increasing evidence suggests that the intrauterine environment is an important determinant of autism risk. This study aims to examine the mid-gestational serum cytokine profiles of the mothers of autistic children from a well-characterised birth cohort.Methods: A nested sub-cohort within a large mother-child birth cohort were identified based on a confirmed multi-disciplinary diagnosis of autism before the age 10 years and neuro-typical matched controls in a 2:1 ratio. IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-17A, GMCSF and TNFα were measured in archived maternal 20-week serum using MesoScale Diagnostics multiplex technology and validation of our IL-17A measurements was performed using an ultrasensitive assay. Results: From a cohort of 2137 children, 25 had confirmed autism before 10 years and maternal serum from mid-gestation. We examined the sera of these 25 cases and 50 matched controls. The sex ratio was 4:1 males to females in each group, and the mean age at diagnosis was 5.09 years (SD 2.13). Concentrations of IL-4 were significantly altered between groups. The other analytes did not differ significantly using either multiplex or ultra-sensitive assays. Conclusions: In a well-characterised prospective cohort of autistic children, and supplementary to promising evidence from animal experiments and retrospective screening programmes, we confirmed mid-gestational alterations in maternal IL-4 cytokine levels in autism affected pregnancies versus matched controls.