Table 2.

Results of 6 meta-analyses included in the study regarding the effectiveness of administering vitamin D supplements.

Study	Study Design	Pico Framework	Results of the Study	Conclusion	VIT. D Supplementation
Cariolou et al. [66]	Systematic review and meta-analysis of observational studies	Participants: In total, 52 studies that included 7434 children from 15 countries hospitalized with acute or critical conditions (sepsis and respiratory tract infections). Intervention: Serum level of vitamin D was analyzed against the RTIs. Comparison: The patients were either with a VDI status (<50 nmol/L) (3473, which accounts for 47.0%) or with a sufficient VD status. Outcome: To evaluate the prevalence of VDD in children with acute or critical conditions.	Of the total number of children in the study, almost half (47%) were VDD with less than 50 nmol/L, with a joint incidence rate estimation of 54.6% (48.5% to 60.6%). After ignoring studies with a small number of patients, the authors found out that the frequency of infections was comparable to the above findings, with 51.5%.	As 2463 young patients were at risk of mortality, this review (that included 18 cohort studies) revealed that this probability was linked with VDD status. Thus, a lower mortality rate can be achieved if children with VDD receive supplementation doses to normalize their VD level.	YES
Hong et al. [67]	Prospective birth cohort study	Participants: In total, 2244 infants monitored from birth to 6 months of age divided into four groups according to the frequency of VD supplementation Intervention: For the first 6 months of life, infants received every day a 400 to 600 IU dose of 25(OH)D. Comparison: The frequency of supplementation was from 0 to 5 to 7 days per week. Outcome: To assess the first episode of pediatrician-diagnosed RTI, or to determine if, in the first 6 months, children had no RTI events.	Infants without vitamin D supplements had their first RTI episode on average 60 days after birth, whereas those receiving supplements had it when they were older than 6 months. According to the authors, the risk ratios in the supplementing group that took supplements 5–7 days per week were 0.46 and 0.18, respectively, showing an inverse association between supplementation periods of time and the risk for various respiratory tract infections that would need hospitalization.	Infants who received vitamin D supplements in the first six months of life saw the onset of the first RTI later than those who did not. For all children without supplements, the median time until their first RTI was 60 days. For exclusively breastfed newborns, it was 36 days and for formula-fed infants it was 90 days.	YES
Pham et al. [68]	Systematic review and meta-analysis of observational studies	Participants: In total, 14 studies were included in a meta-analysis evaluating the ARTIs risk, and a further 5 were analyzed for severity of symptoms. Intervention: Blood 25 hydroxycholecalciferol was measured. Comparison: Blood levels were compared with the risk of developing RTIs. Outcome: To assess the risk and severity of ARTI in children with VDI or VDD.	When comparing the lowest to the highest 25(OH)D category, the pooled odds ratios were 1.83 and 2.46, respectively, showing an inverse relationship between 25(OH)D and risk and development of ARTIs. The likelihood of infections rose by 1.02 for every 10 nmol/L of 25(OH)D drop in serum. This was a straightforward trend, as and the risk of ARTIs increased most dramatically when the VD concentration was below 37.5 nmol/L.	According to the research, vitamin D significantly reduces the likelihood and severity of ARTIs, particularly in those with low concentrations. Still, finding the ideal concentration or the level below which supplementation would be beneficial proved difficult.	YES
Anitua et al. [69]	Systematic review and meta-analysis of observational studies	Participants: In total, 65 studies were deemed eligible, with a total of 50,554 participants. Intervention: 25(OH)D was determined from blood samples Comparison: The results were compared with the risk of developing RTIs. Outcome: To assess the risk and severity of ARTI in children with VDI or VDD.	Many studies stated that vitamin D supplementation reduced the risk of respiratory infections among all participants. Consequently, the protective effect of vitamin D was only substantial when taken regularly.	According to incidence count data, this meta- concluded that the incidence of upper and lower respiratory tract infections was noticeably decreased by vitamin D prevention.	YES
Kumar et al. [70]	Systematic review and meta-analysis of RCTs	Participants: In total, 18 RCTs totaling 1579 participants were included in this study. Intervention: Supplementing with vitamin D in addition to the treatment for asthma Comparison: Placebo groups were compared to the intervention groups Outcome: To assess the risks and severity of asthma in children in relation to their vitamin D status.	This meta-analysis included randomized control trials with VDI children whose levels were below 20 nmol/L. However, information on asthma aggravation was only given by one research, where vitamin D supplementation had no detectable impact on any of the outcomes that were reported. Other results did not significantly alter in any way. Using the fixed-effect model, the authors conducted a sensitivity analysis for results with heterogeneity of less than 50%. The conclusion was that these groups had no difference in any of the outcomes.	Vitamin D supplementation had no noticeable impact on asthma episodes needing systemic corticosteroids, according to the collective RCTs included in this research. Furthermore, there was no obvious change in the proportion of children experiencing asthma episodes. Therefore, vitamin D does not lessen the need for hospital stays and urgent care visits. There is little evidence to support the idea that vitamin D supplementation may be protective in children with asthma.	NO
Fang et al. [71]	Systematic review and meta-analysis of observational studies	Participants: Four trials totaling 13.367 participants examined the effectiveness of vitamin D in avoiding ARTIs. Intervention: The concentration of vitamin D was determined. Comparison: Infection rates between the VD groups and control ones. Outcome: To find out if there is any association between a higher dose of vitamin D and the incidence and outcome of ARTIs in children.	With 1.596 participants, two studies investigated the effectiveness of higher vs. regular supplementation doses of 25(OH)D when it comes to preventing ARTIs. There were few obvious differences between the two groups, and the included trials lacked substantial heterogeneity. Because the influenza A infection was reported in many studies utilizing different treatment arms, only that illness could be the subject of a meta-analysis. Compared to the lower dose of the VD group, the higher one had some decline in influenza A rates.	Investigating the effectiveness of vitamin D supplementation in preventing these illnesses produced mixed findings. According to this research, vitamin D administration offers no noticeable advantage over a placebo in terms of considerably lowering ARTI rates, but it did show some improvement when it came to the Influenza A virus. Furthermore, a high amount of vitamin D had no advantages over administering the recommended quantity. Additionally, in most infections recorded, the frequencies of various viral infections were equally independent of the regimen or organism that caused the illness.	NO