Maternal mid-pregnancy C-reactive protein and risk of autism spectrum disorders: the early markers for autism study
O Zerbo1, M Traglia2, C Yoshida1
1Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Insights
Maternal C-reactive protein (CRP) levels during pregnancy were unexpectedly lower in mothers of children with autism spectrum disorder (ASD), suggesting a decreased risk of ASD with higher CRP. Further research is needed to understand this association.
Area of Science:
- Immunology
- Neurodevelopmental Disorders
- Genetics
Background:
- Maternal C-reactive protein (CRP) levels during pregnancy have been linked to autism spectrum disorder (ASD) risk in offspring.
- Previous studies suggest a potential association, but the direction and mechanism remain unclear.
Purpose of the Study:
- To investigate the association between maternal CRP levels in mid-pregnancy and the risk of ASD in offspring.
- To explore potential genetic associations with CRP levels and ASD risk.
Main Methods:
- Population-based nested case-control study.
- Included 500 children with ASD, 235 with developmental delay (DD), and 580 general population (GP) controls.
- Measured maternal CRP in serum from 15-19 weeks of gestation; analyzed genome-wide single-nucleotide polymorphism (SNP) data.
Main Results:
- Maternal CRP levels were lower in mothers of children with ASD compared to controls.
- Higher CRP levels (upper third and fourth quartiles) were associated with a 45% and 44% decreased risk of ASD, respectively.
- No significant difference in maternal CRP levels was observed between mothers of children with DD and controls. Two SNPs at the CRP locus were associated with CRP levels but not ASD.
Conclusions:
- Lower mid-pregnancy maternal CRP levels may be associated with an increased risk of ASD, contrary to previous hypotheses.
- The observed association might be related to altered maternal immune responses.
- Biological mechanisms require further elucidation.
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.
