Association of neonatal blood levels of brain-derived neurotrophic factor with development of autism spectrum disorder:a systematic review and meta-analysis

Background Our goal was to evaluate the association between neonatal blood brain-derived neurotrophic factor(BDNF)level and autism spectrum disorder(ASD)diagnosis later in life.Methods MEDLINE and Web of Science databases were searched from inception until September 16,2020.Reference lists of all relevant articles also were reviewed.Mean blood BDNF concentrations,standard deviations,sample sizes,and other data needed for calculation of effect sizes were extracted by two independent investigators.The quality of the included studies was appraised using the Newcastle-Ottawa Scale for case-control studies.Data were pooled using the random-effects model.Results Five case-control studies involving 1341 cases and 3395 controls were included in the meta-analysis.The meta-analysis of all included studies showed no significant difference in blood BDNF levels between neonates diagnosed with ASD later in life and healthy controls[standardized mean difference(SMD)=0.261;95%confidence interval(CI)-0.052 to 0.573;P=0.102],with high level of heterogeneity(Q=64.346;I2=93.784;P<0.001).A subgroup analysis by assay type showed decreased blood BDNF levels in ASDs compared to controls(SMD=—0.070;95%CI-0.114 to-0.026;P=0.002),with high level of homogeneity(Q=0.894;I2=0.000;P=0.827).No evidence of publication bias was observed.Conclusions Neonates diagnosed with ASD later in life have decreased blood levels of BDNF measured by double-antibody immunoassay.More studies are warranted to facilitate a more robust conclusion.