Association between peripheral blood levels of C-reactive protein and Autism Spectrum Disorder in children: A systematic review and meta-analysis

Abstract

Introduction: In the past five years, a growing number of studies have tried to illustrate the association between the peripheral blood level of C-reactive protein (CRP) and Autism Spectrum Disorders (ASD). However, the results have been inconsistent. To assess whether abnormal CRP in peripheral blood was associated with ASD, we conducted a systematic review and meta-analysis.

Methods: A systematic literature search was performed using the Embase, PubMed, Web of Knowledge, PsycINFO, and Cochrane databases through August 27, 2019. Reference lists were also checked by hand-searching. Clinical studies exploring CRP concentration in the peripheral blood of autistic children and healthy controls were included in our meta-analysis. Overlapping samples were excluded. We pooled obtained data using a fixed- or random-effect model based on a heterogeneity test with Comprehensive Meta-Analysis software and STATA software. Standardized mean differences were converted to Hedges' g statistic in order to obtain the effect size adjusted for sample size. Subgroup analyses, sensitivity analyses, meta-regression, and publication bias tests were also undertaken.

Results: Nine studies with 592 ASD children and 604 healthy children were included in our meta-analysis. Significantly elevated CRP levels in peripheral blood were found in ASD children compared with healthy controls (Hedges' g = 0.527, 95% CI: 0.224-0.830, p = 0.001). Subgroup analyses based on sample types and ethnicity also showed similar results, except for the plasma subgroup. There was also a significant association between peripheral CRP concentration and ASD after removing the studies identified by Galbraith plots. The results of the sensitivity analysis revealed that no single study could reverse our results. Meta-regression analyses revealed that the gender of autistic children had a moderating effect on the outcome of the meta-analysis. In addition, no obvious publication bias was found in the meta-analysis.

Conclusions and relevance: In our study, peripheral CRP levels were significantly elevated in autistic children compared with healthy children. These results may provide us some new insights about ASD.

Keywords: Autism Spectrum Disorders; C-reactive protein; Peripheral blood.