Peripheral blood neurotrophic factor levels in children with autism spectrum disorder: a meta-analysis

Abstract

Increasing evidence suggests that abnormal regulation of neurotrophic factors is involved in the etiology and pathogenesis of Autism Spectrum Disorder (ASD). However, clinical data on neurotrophic factor levels in children with ASD were inconsistent. Therefore, we performed a systematic review of peripheral blood neurotrophic factors levels in children with ASD, and quantitatively summarized the clinical data of peripheral blood neurotrophic factors in ASD children and healthy controls. A systematic search of PubMed and Web of Science identified 31 studies with 2627 ASD children and 4418 healthy controls to be included in the meta-analysis. The results of random effect meta-analysis showed that the peripheral blood levels of brain-derived neurotrophic factor (Hedges' g = 0.302; 95% CI = 0.014 to 0.591; P = 0.040) , nerve growth factor (Hedges' g = 0.395; 95% CI = 0.104 to 0.686; P = 0.008) and vascular endothelial growth factor (VEGF) (Hedges' g = 0.097; 95% CI = 0.018 to 0.175; P = 0.016) in children with ASD were significantly higher than that of healthy controls, whereas blood neurotrophin-3 (Hedges' g = - 0.795; 95% CI = - 1.723 to 0.134; P = 0.093) and neurotrophin-4 (Hedges' g = 0.182; 95% CI = - 0.285 to 0.650; P = 0.445) levels did not show significant differences between cases and controls. Taken together, these results clarified circulating neurotrophic factor profile in children with ASD, strengthening clinical evidence of neurotrophic factor aberrations in children with ASD.

Figure 1

PRISMA flowchart of the literature search.

Figure 2

Forest plot for random-effects meta-analysis for BDNF. Forest plot for random-effects meta-analysis on differences in blood BDNF concentrations between children with autism spectrum disorder (ASD) and healthy controls. The sizes of the squares are proportional to study weight. Diamond marker indicates pooled effect size. CI, confidence interval.

Figure 3

Forest plot for random-effects meta-analysis for NGF, VEGF, NT-3 and NT-4. Forest plot for random-effects meta-analysis on differences in blood NGF (A), VEGF (B), NT-3 (C) and NT-4 (D) concentrations between children with autism spectrum disorder (ASD) and healthy controls. The sizes of the squares are proportional to study weight. Diamond marker indicates pooled effect size. CI, confidence interval.