Vitamin D for Autism Spectrum Disorders:a Protocol for Systematic Review and Meta-analysis

Abstract

\n IntroductionAutism spectrum disorder(ASD) is a neurodevelopmental disorder characterized by repetitive and stereotypic behavior, impaired social interactions and communications. An increasing number of reseachers suggested that vitamin D may be participated in the pathogenesis of ASD, and vitamin D deficiency may be one of the causes of ASD.Meanwhile, some studies have shown that vitamin D can improve the core symptoms in ASD children.On top of updating the latest systematic review on vitamin D supplementation and ASD, we aim to conduct the meta-analyses of trials on vitamin D3 supplementation and ASD. Besides, we will conduct for the first time subgroup analyses based on individual patient data collected from randomised controlled trials.Methods and analysisA systematic review and individual patient data meta-analysis on randomised placebo-controlled trials with a vitamin D3 intervention. All studies are searched from inception without time restriction. The addressed outcomes are 25-hydroxyvitamin D, Childhood Autism Rating Scaleas(CARS), Autism Behavior Checklist (ABC), Social Responsiveness Scale(SRS) and M-CHAT. Trial results will be reanalysed using Cox proportional hazard regression models and meta-analyses are performed. Cochran’s Q-Test and the I2 index will be used to statistically assess the level of heterogeneity, while sensitivity and subgroup analyses serve to identify potential causes of heterogeneity. Subgroup analyses will be conducted for age, sex, 25-hydroxyvitamin D level,vitamin D3 dosing, follow-up time,and the core symptoms of ASD. Publication bias will be assessed by funnel plots and Egger’s test. Ethics and disseminationEthical approval is not required since no human beings are involved in this systematic review. Results will be published in a peer-reviewed journal with open access. Strengths and limitations of this study1.Meta-analysis on vitamin D and ASD,we not only study the relationship between vitamin D deficiency and the occurrence of ASD, the preventive and therapeutic effects of vitamin D on ASD, but also the influence factors of vitamin D supplementation on the therapeutic effect of ASD. 2.Assess study quality, sources of heterogeneity and bias minimise the risk of bias and will gather reproducible results.3.Eligible data for meta-analysis may be limited.PROSPERO registration number:CRD42021264097