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Association Between Peripheral Blood Levels of Vitamin A and Autism Spectrum Disorder in Children: A Meta-Analysis

ABSTRACT: Vitamin A is an essential fat-soluble micronutrient that plays important roles in a surprisingly wide variety of biological processes from early growth and development to brain maintenance. Numerous clinical studies have been conducted to explore the relationship between peripheral vitamin A levels and autism spectrum disorder (ASD), but the results of these studies are controversial. Therefore, we assessed the association between peripheral vitamin A levels and ASD in the present meta-analysis. Relevant records were retrieved through the Embase, Web of Knowledge and PubMed databases up to 13 November 2020. Reference lists were also searched and analyzed. Hedges' g with its corresponding 95% confidence interval (CI) was used to assess the association between peripheral vitamin A levels and ASD. A fixed or random effects model was selected according to a heterogeneity test in overall and subgroup analyses. Five records (six studies) with 935 ASD children and 516 healthy children were included in the present study. Significantly decreased peripheral vitamin A concentrations were observed in ASD children compared with healthy children (Hedges' g = −0.600, 95% CI −1.153 to −0.048, P = 0.033). A similar result was also obtained after removing the studies identified by Galbraith plots. In addition, no obvious publication bias was found in the meta-analysis. The findings of our meta-analysis suggested decreased peripheral vitamin A levels in ASD children compared with healthy children. Further investigations into the effects of vitamin A on the development of ASD are warranted.

SUBMITTER: Wang N

PROVIDER: S-EPMC8515042 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background:The endocannabinoid system (ECS) is a major regulator of synaptic plasticity and neuromodulation. Alterations of the ECS have been demonstrated in several animal models of autism spectrum disorder (ASD). In some of these models, activating the ECS rescued the social deficits. Evidence for dysregulations of the ECS in human ASD are emerging, but comprehensive assessments and correlations with disease characteristics have not been reported yet. Methods:Serum levels of the main endocannabinoids, N-arachidonoylethanolamine (AEA or anandamide) and 2-arachidonoylglycerol (2-AG), and their related endogenous compounds, arachidonic acid (AA), N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA), were analyzed by liquid chromatography/tandem mass spectrometry in 93 children with ASD (age = 13.1 ± 4.1, range 6-21; 79% boys) and 93 age- and gender-matched neurotypical children (age = 11.8 ± 4.3, range 5.5-21; 79% boys). Results were associated with gender and use of medications, and were correlated with age, BMI, and adaptive functioning of ASD participants as reflected by scores of Autism Diagnostic Observation Schedule (ADOS-2), Vineland Adaptive Behavior Scale-II (VABS-II), and Social Responsiveness Scale-II (SRS-2). Results:Children with ASD had lower levels (pmol/mL, mean ± SEM) of AEA (0.722 ± 0.045 vs. 1.252 ± 0.072, P < 0.0001, effect size 0.91), OEA (17.3 ± 0.80 vs. 27.8 ± 1.44, P < 0.0001, effect size 0.94), and PEA (4.93 ± 0.32 vs. 7.15 ± 0.37, P < 0.0001, effect size 0.65), but not AA and 2-AG. Serum levels of AEA, OEA, and PEA were not significantly associated or correlated with age, gender, BMI, medications, and adaptive functioning of ASD participants. In children with ASD, but not in the control group, younger age and lower BMI tended to correlate with lower AEA levels. However, these correlations were not statistically significant after a correction for multiple comparisons. Conclusions:We found lower serum levels of AEA, PEA, and OEA in children with ASD. Further studies are needed to determine whether circulating endocannabinoid levels can be used as stratification biomarkers that identify clinically significant subgroups within the autism spectrum and if they reflect lower endocannabinoid "tone" in the brain, as found in animal models of ASD.

Dataset Information

Association Between Peripheral Blood Levels of Vitamin A and Autism Spectrum Disorder in Children: A Meta-Analysis

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