Maternal mid-pregnancy C-reactive protein and risk of autism spectrum disorders: the early markers for autism study.
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.
Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
O
O
Zerbo
Department of Psychiatry and Institute of Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
M
M
Traglia
Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
C
C
Yoshida
Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA, USA.
L S
LS
Heuer
Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA, USA.|MIND Institute, University of California, Davis, Sacramento, CA, USA.
P
P
Ashwood
Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
G N
GN
Delorenze
Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA, USA.|Department of Pediatrics, University of California, Medical Health System, Sacramento, CA, USA.
R L
RL
Hansen
Environmental Health Investigations Branch, California Department of Public Health, Richmond, CA, USA.
M
M
Kharrazi
Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA, USA.|Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, CA, USA.
J
J
Van de Water
Stanley Division of Developmental Neurovirology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
R H
RH
Yolken
Department of Psychiatry and Institute of Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
L A
LA
Weiss
Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
L A
LA
Croen
D000328:Adult; D000067877:Autism Spectrum Disorder / Q000453:epidemiology*; D002097:C-Reactive Protein / Q000032:analysis*; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009035:Mothers; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D012306:Risk; D055815:Young Adult
D002097:C-Reactive Protein