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Elevated maternal C-reactive protein and autism in a national birth cohort

Abstract

Autism is a complex neuropsychiatric syndrome with a largely unknown etiology. Inflammation during pregnancy may represent a common pathway by which infections and other insults increase risk for the disorder. Hence, we investigated the association between early gestational C-reactive protein (CRP), an established inflammatory biomarker, prospectively assayed in maternal sera, and childhood autism in a large national birth cohort with an extensive serum biobank. Other strengths of the cohort included nearly complete ascertainment of pregnancies in Finland (N=1.2 million) over the study period and national psychiatric registries consisting of virtually all treated autism cases in the population. Increasing maternal CRP levels, classified as a continuous variable, were significantly associated with autism in offspring. For maternal CRP levels in the highest quintile, compared with the lowest quintile, there was a significant, 43% elevated risk. This finding suggests that maternal inflammation may have a significant role in autism, with possible implications for identifying preventive strategies and pathogenic mechanisms in autism and other neurodevelopmental disorders.

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Acknowledgements

This manuscript was supported by grants R01 ES019004-03 (A.S.B.) from the National Institute of Environmental Health Sciences, K02 MH065422-09 (A.S.B.) from the National Institute of Mental Health, a grant from Autism Speaks (A.S.), and the State Research Institute (National Institute of Health and Welfare). We wish to acknowledge the following individuals for their contributions to this work: Jaana Leiviskä for performing the CRP analysis, Finnish Maternity Cohort laboratory staff for retrieving and preparing the samples for analysis, Jacky Chow and Patric Prado for manuscript preparation, and Yuanyuan Bao for data consultation.

Author Contributions

Dr Brown contributed to hypothesis generation, study design, data analysis and manuscript writing. Dr Sourander contributed to hypothesis generation, study design, data collection, and manuscript writing. Dr Hinkka-Yli Salomäki contributed to the study design, data analysis, and manuscript writing. Dr McKeague contributed to the study design, data analysis, and manuscript writing. Dr Sundvall contributed to study design, supervision of the CRP assay and manuscript writing. Dr Surcel contributed to hypothesis generation, study design, data collection and manuscript writing.

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Correspondence to A S Brown.

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Brown, A., Sourander, A., Hinkka-Yli-Salomäki, S. et al. Elevated maternal C-reactive protein and autism in a national birth cohort. Mol Psychiatry 19, 259–264 (2014). https://doi.org/10.1038/mp.2012.197

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  • DOI: https://doi.org/10.1038/mp.2012.197

Keywords

  • Autism
  • prenatal
  • C-reactive protein
  • infection
  • inflammation
  • cytokines

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