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.
Highlights
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with unknown cause(s) for the vast majority of cases
There was no difference between the ASD cases and the general population (GP) controls for gestational age and maternal weight at blood draw
We found no association between maternal mid-pregnancy C-reactive protein (CRP) levels and risk of ASD in the smaller sample, but in the larger sample, the mothers of children with ASD had lower levels of mid-pregnancy CRP compared with those of GP controls
Summary
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with unknown cause(s) for the vast majority of cases. Among the suspected environmental factors of autism, maternal infections during pregnancy have been reported by a number of epidemiological studies.[10,11,12,13,14,15] The studies using animal models have shown an association between maternal infection during pregnancy and abnormal behaviors in offspring[16,17] and suggested that maternal immune activation might be one pathway by which maternal infection can lead to elevated risk of autism in the offspring.[18] Fever, an acute inflammatory response to various environmental factors including infections, has been suggested to increase the risk of autism and developmental delays.[10,14]
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