Maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders: a systematic review

Abstract

Inflammation is increasingly recognized as a cause or consequence of common problems of humanity including obesity, stress, depression, pollution and disease states such as autoimmunity, asthma, and infection. Maternal immune activation (MIA), triggered by both acute and systemic chronic inflammation, is hypothesized to be one of the mechanisms implicated in the pathogenesis of neurodevelopmental disorders (NDD). Although there is substantial preclinical evidence to support the MIA hypothesis, the human evidence is disparate. We performed a systematic review on human studies examining associations between maternal inflammatory states and offspring NDDs (autism spectrum disorder- ASD, attention deficit hyperactivity disorder-ADHD, Tourette syndrome-TS). 32 meta-analyses and 26 additional individual studies were identified. Maternal states associated with ASD include obesity, gestational diabetes mellitus, pre-eclampsia, pollution, stress, depression, autoimmune diseases, and infection. Maternal states associated with ADHD include obesity, pre-eclampsia, smoking, low socioeconomic status (SES), stress, autoimmune disease, and asthma. Maternal states associated with TS include low SES, depression, and autoimmune diseases. Diverse maternal inflammatory states in pregnancy are associated with common offspring NDDs. Given the increased prevalence of NDDs, there is urgent need to explore relative and cumulative maternal risk factors and disease mechanisms. Defining preventable risk factors in high-risk pregnancies could mitigate the expression and severity of NDDs.

Understanding the impact of SNPs associated with autism spectrum disorder on biological pathways in the human fetal and adult cortex

“…The existence of changes within fetal cortex pathways for endogenous antigens (e.g. viral) lends some support the hypothesis that the risk of ASD may be greater among children whose mothers suffered from infectious or immune-related diseases during pregnancy—when the infant brain is developing 60 – 63 .…”

Betamethasone administration during pregnancy is associated with placental epigenetic changes with implications for inflammation

“…In fact, FKBP51 has been shown to moderate immune pathways [ 49 ] via for example direct interaction with regulators of the alternative NFkappaB pathways leading to a proinflammatory immune response [ 50 ]. This is of interest, given the fact that long-term effects of BET have been associated with childhood mental and behavioral disorders [ 18 ] and that maternal inflammation has indeed been suggested as possible mediator between maternal stress and offspring neuropsychiatric risk [ 51 , 52 ]. This may extend to placental inflammation.…”

Correlation analysis of expression of CC and CXC chemokines in children with autism spectrum disorder

“…[ 16 , 17 ] Han et al demonstrated that maternal inflammatory states were linked with neurodevelopmental disorders, including ASD. [ 18 ] Therefore, dysfunctional immune defenses and inflammatory reactions in children with ASD could be important precipitating factors for triggering this disorder.…”

“…The findings in this study are consistent with those reported by Zerbo et al, [ 22 ] who showed that compared with healthy children, children with ASD showed increased serum MCP-1 levels and decreased RANTES levels. In addition, Han et al [ 18 ] documented that the levels of MCP-1 and RANTES in children with ASD were significantly higher than those in normally developing children, whereas the levels of IL-8, IP-10, and MIG are significantly lower in autistic children than in normal children. The variations in IL-8, IP-10, and MIG levels are consistent with the results of our study; however, the result of the RANTES level is contrary to our findings.…”