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AIM To evaluate the published literature on the use of antioxidants in improving developmental outcomes in DS children METHODS The systematic review included interventional studies (randomized controlled trials (RCTs) and quasi-RCTs (q-RCTs)) on children between the ages of 0 to 18 years diagnosed with DS and used antioxidants for improving developmental outcomes, and compered with similar children given placebo or no supplementation. Aim was to have a true randomized population for intervention, thus RCTs and quasi-RCTs were included. Studies were excluded if those were non-randomized controlled studies (including observational studies, systematic and narrative review articles, editorials and commentaries) with no random allocation and no comparison group. We also excluded studies if data from participants with DS was included as part of a larger group of participants (e.g. children with intellectual disability) and could not be separated for subgroup analysis, and studies that did not assess developmental domains and only assessed biochemical markers. The review included children with other conditions associated with developmental disability, only when data for children with DS were separately reported. RESULTS Eleven RCTs and q-RCTs ful lled the eligibility criteria with 683 participants with Down syndrome, with age range of newborns to 17 years of age. Eight studies did not show any statistically signi cant clinical bene t of using antioxidants. A metaanalysis was applied to compare changes in the effect sizes (post and pre-intervention) in GDQ between the intervention and control groups. The forest plot including the three studies doesn't demonstrate a statistically signi cant improvement. INTERPRETATION This review concludes that the use of antioxidants does not improve the developmental outcomes in pediatric population with DS.

AIM To evaluate the published literature on the use of antioxidants in improving developmental outcomes in DS children METHODS The systematic review included interventional studies (randomized controlled trials (RCTs) and quasi-RCTs (q-RCTs)) on children between the ages of 0 to 18 years diagnosed with DS and used antioxidants for improving developmental outcomes, and compered with similar children given placebo or no supplementation. Aim was to have a true randomized population for intervention, thus RCTs and quasi- RCTs were included. Studies were excluded if those were non-randomized controlled studies (including observational studies, systematic and narrative review articles, editorials and commentaries) with no random allocation and no comparison group. We also excluded studies if data from participants with DS was included as part of a larger group of participants (e.g. children with intellectual disability) and could not be separated for subgroup analysis, and studies that did not assess developmental domains and only assessed biochemical markers. The review included children with other conditions associated with developmental disability, only when data for children with DS were separately reported. RESULTS Eleven RCTs and q-RCTs fulfilled the eligibility criteria with 683 participants with Down syndrome, with age range of newborns to 17 years of age. Eight studies did not show any statistically significant clinical benefit of using antioxidants. A meta-analysis was applied to compare changes in the effect sizes (post and pre-intervention) in GDQ between the intervention and control groups. The forest plot including the three studies doesn’t demonstrate a statistically significant improvement. INTERPRETATION This review concludes that the use of antioxidants does not improve the developmental outcomes in pediatric population with DS.

The COVID-19 pandemic has prompted the urgent development and distribution of novel vaccinations to reduce the global disease burden and establish herd immunity. Vaccination is a cost-effective public health measure that is critical for disease prevention; as of March 2022, Health Canada has authorized the distribution of the Pfizer-BioNTech and Moderna mRNA COVID-19 vaccines in pediatric populations. However, vaccine hesitancy among caregivers remains a significant barrier to vaccine uptake in the pediatric population. Increased research on the intentions, motivations, and perceptions of pediatric COVID-19 vaccine efficacy and safety may facilitate the development of public health strategies to address pediatric vaccine knowledge translation, accessibility, and administration barriers. This perspective paper aims to explore the major barrier of vaccine hesitancy and potential solutions to achieve effective vaccine uptake in the Canadian pediatric population.