Mid-gestation cytokine profiles in mothers of children affected by autism spectrum disorder: a case–control study

Abstract

Autism Spectrum disorder is one of the commonest and most important neurodevelopmental conditions affecting children today. With an increasing prevalence and an unclear aetiology, it is imperative we find early markers of autism, which may facilitate early identification and intervention. 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. 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. From a cohort of 2137 children, 25 had confirmed autism before 10 years and stored 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). We found that concentrations of IL-4 were significantly altered between groups. The other analytes did not differ significantly using either multiplex or ultra-sensitive assays. In our well-characterised prospective cohort of autistic children, we confirmed mid-gestational alterations in maternal IL-4 concentrations in autism affected pregnancies versus matched controls. These findings add to promising evidence from animal models and retrospective screening programmes and adds to the knowledge in this field.

Maternal Levels of Cytokines in Early Pregnancy and Risk of Autism Spectrum Disorders in Offspring

“…In a recent case-control study, Carter et al ( 26 ) investigated the association between eight maternal cytokines measured at 20 weeks of gestation in 25 mothers to ASD-cases and 50 mothers to controls, matched by infant sex, gestational age, birthweight and maternal BMI. The median cytokine concentrations were compared between groups using non-parametric tests.…”

“…Several previous studies have investigated maternal cytokines during pregnancy related to offspring risk of ASD, all use samples collected in mid-pregnancy ( 23 – 26 ). The results are inconsistent, with significant findings failing to replicate across studies, for example, both elevated and decreased levels of IL-4 have been reported among mothers to ASD-cases ( 23 , 26 ). However, there are substantial differences related to design and methodology, and only one of the studies used clinically evaluated cases in a large population-based sample.…”

Insights on dental care management and prevention in children with autism spectrum disorder (ASD). What is new?

“…A recent paper, based on the national Swedish birth registry from 2007 to 2018, assessed that of 383 preterm infants born at a median age of 23.3 weeks, about 24% further developed ASD and 30% attention deficit hyperactivity disorder (ADHD) ( 77 ). Many attempts, including the investigation of the immune and cytokine profile of pregnant mothers ( 78 ), are in the spotlight. The early diagnosis of the autistic syndrome should encourage a prompt series of consultations and actions to safeguard children's oral health and prevent problems that may compel parents to resort to burdensome dental interventions.…”

Data_Sheet_1.pdf

“…Several previous studies have investigated maternal cytokines during pregnancy related to offspring risk of ASD, all use samples collected in mid-pregnancy (23)(24)(25)(26). The results are inconsistent, with significant findings failing to replicate across studies, for example, both elevated and decreased levels of IL-4 have been reported among mothers to ASD-cases (23,26). However, there are substantial differences related to design and methodology, and only one of the studies used clinically evaluated cases in a large population-based sample.…”