Maternal mid-pregnancy C-reactive protein and risk of autism spectrum disorders: the early markers for autism study

Abstract

Maternal pregnancy levels of the inflammatory marker C-reactive protein (CRP) has been previously associated with autism spectrum disorder (ASD) in the offspring. We conducted a population-based nested case–control study with 500 children with ASD, 235 with developmental delay (DD) and 580 general population (GP) controls to further investigate whether elevated CRP during pregnancy increases the risk of ASD. Maternal CRP concentration was measured in archived serum collected during 15–19 weeks of pregnancy and genome-wide single-nucleotide polymorphism (SNP) data were generated. The levels of CRP were compared between ASD vs GP and DD vs GP. The genetic associations with CRP were assessed via linear regression. Maternal CRP levels in mid-pregnancy were lower in mothers of ASD compared with controls. The maternal CRP levels in the upper third and fourth quartiles were associated with a 45 and 44% decreased risk of ASD, respectively. Two SNPs at the CRP locus showed strong association with CRP levels but they were not associated with ASD. No difference was found between maternal CRP levels of DD and controls. The reasons for the lower levels of CRP in mothers of ASD are not known with certainty but may be related to alterations in the immune response to infectious agents. The biological mechanisms underlying this association remain to be clarified.

Maternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates

“…A subsequent study found that maternal infections diagnosed in a hospital setting, presumably associated with more severe infections, were associated with an increased risk of ASD, while infections diagnosed in outpatient settings were not associated ASD (23). Quantification of cytokines, chemokines and other inflammatory markers obtained from archived maternal sera (24, 25) and amniotic fluid (26, 27) lends further support to the link between maternal infection and increased ASD risk, though studies have yielded mixed results (28, 29). Although there is a clear need for additional epidemiological studies, the current data suggest that, at least for a subset of women, exposure to infection during pregnancy may increase the risk of ASD or other CNS disorders (30, 31).…”

Concentrations of immune marker in newborn dried blood spots and early childhood development: Results from the Upstate KIDS Study

“…For example, Brown et al showed that higher levels of maternal CRP during first and early second trimester of pregnancy was associated with a diagnosis of ASD in children. In contrast, a similar study found that maternal CRP levels in mid‐pregnancy were lower in mothers of ASD children compared with controls . Koks et al reported that the observed association between maternal CRP and children's autistic traits was largely explained by sociodemographic and maternal health‐related factors.…”

Immune dysfunction and neuroinflammation in autism spectrum disorder

“…The pathogenesis of ASD is complex and controversial, and both nutritional and immune causes have been recently associated with this complex pathology (Hsiao 2013, Endreffy et al 2016, Fujiwara et al 2016, Zerbo et al 2016. Controversial issues arose from attempting to distinguishing between children's and adults ASD, and particularly Asperger syndrome with high functioning autism in adults, where language delays may be used to distinguish the two pathologies, as the poor performance on language tests also challenges the assumption that early language development in Asperger syndrome is essentially normal (Howlin 2003, Baron-Cohem andWheelwright 2004).…”