Meta-analysis of the effects of vitamin D on growth, development and body weight of children of different ages

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Vitamin D drops could effectively promote children’s growth and development, but there was no comprehensive analysis of the effects of vitamin D drops on children’s growth and development. We want to systematically evaluate the effects of vitamin D drops on different ages of children’s growth and development by meta-analysis. Methods PubMed, EMBASE and Cochrane Library as search databases was collected from January 2000 to June 2023. The randomized controlled trials (RCTs) on the effects of vitamin D on children’s growth and development were searched, the literatures were screened, the data (height and weight) were extracted, and the risk of bias in the included studies was evaluated. The meta-analysis was conducted using Stata. 11 software. Results We included six studies, all randomized controlled trials of the effects of vitamin D supplementation on growth and development in children. The results showed that compared with the placebo group in the control group, vitamin D supplementation could significantly improve the level of serum 25(OH)D3 in children [n = 603, mean difference (MD) = 5.08 ng/ml, 95%CI (0.57,9.60), P = 0.03]. BMI, height, body weight and relative fat index had little effect, and there was no significant comparison between groups, which were [n = 1514, MD=-0,08 kg/m2, 95%CI (-0.47,0.30), P = 0.67], respectively. [n = 1426, MD = 0.18 cm, 95% CI (0.61, 0.97), P = 0.66). (n = 1426, MD = 0.10 kg, 95% CI (0.43, 0.22), P = 0.53) and (n = 1127, MD = 0.88%, 95% CI (26.24, 24.47), P = 0.95). Conclusion The study suggests that while vitamin D supplementation effectively boosts serum 25(OH)D3 levels in children, it has limited influence on other growth and development parameters such as BMI, height, body weight, and relative fat index. Vitamin D Children Growth and development Meta analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Nutrient deficiency is an important factor affecting children’s growth and development. Many studies showed that the dietary structure of many children was unreasonable, resulting in insufficient intake of calcium, vitamin D and other nutrients [ 1 – 2 ]. Children’s long-term lack of calcium, vitamin D and other nutrients could lead to growth retardation [ 3 ]. Vitamin D can effectively promote calcium absorption, participate in bone formation, and help promote children’s bone development [ 4 ]. Vitamin D is essential nutrients for human growth and development, especially for the development of fetuses and infants [ 5 ]. Vitamin D is a trace element that promotes children’s healthy growth. It plays a major role in promoting calcium absorption and ensuring bone strength. It also plays an important role in the prevention of many diseases in adulthood [ 6 – 7 ]. Vitamin D can increase the absorption of calcium by the body, and has a positive role in promoting the growth and development of children. Moreover, vitamin D has an important regulatory function on the immune function of the human body [ 8 ]. Vitamin D deficiency has been linked to a number of health problems in children and adolescents, including an increased risk of rickets, asthma, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, infections, and type 1 diabetes. Vitamin D supplementation has also been shown to have a beneficial effect in preventing and/or ameliorating most of these diseases [ 9 ]. Childhood overweight and obesity remain a major health problem worldwide. A meta-analysis showed that body weight/fat mass was inversely associated with vitamin D status in the general population and in children [ 10 ]. The association between vitamin D supplementation and body weight weakens with age and has a significant impact on the height and weight of growing children [ 11 ]. However, the results of different randomized controlled clinical trials have shown that vitamin D supplementation may increase body weight and reduce fat mass in children, but some studies have not found significant effects. However, most of the studies have shortcomings such as small sample size, uneven reliability and inconsistent baseline, which leaded to divergent conclusions and lack of uniform clinical standards. Therefore, this study summarizes the effects of vitamin D on children’s growth and development based on meta-analysis. Material and methods Literature search method We searched PubMed, EMBASE and Cochrane Library as search databases, and collected RCT studies on vitamin D. The search period was from January 2000 to June 2023. The search was carried out by combining subject words with free words, and the references included in the research topic were searched. The key words included vitamin D, children’s growth and development. Manual retrieval of relevant journals and retrospective search of references for relevant research. Literature inclusion and exclusion criteria Inclusion criteria : The language of the literature was English. The publication period was from 2000 to June 2022. The research method was a randomized controlled trial (RCT), and the results reported the changes of height and weight after the intervention. The intervention subjects were children aged 0–14 years, and the intervention time was more than 8 weeks. Exclusion criteria : Papers with duplicate contents; unable to extract analysis data; the type of study was non randomized trial, and there was not enough data to calculate the change value; the included subjects had chronic diseases affecting growth and development, such as protein energy malnutrition and anemia. Literature screening and excerpts In combination with the literature search results, read through the literature that may be related to this study according to the title and abstract, and screen according to the inclusion criteria and exclusion criteria. After discussion, it was decided to add the research literature that meets the criteria in the reading. Establish an information extraction table, including country, author, title, publication years, article source, research object, inclusion criteria, age, number of people, intervention time. The extracted information was a blind method, which was implemented independently by two persons. At least three persons with different opinions discuss and combine the opinions of third-party experts. Document quality In combination with the risk bias assessment method published in the Cochrane manual (2011 Edition), the quality of the included literature was evaluated. The contents include selection bias, implementation bias, measurement bias, follow-up bias and reporting bias. Statistical analysis Revman5.2 software was selected. The heterogeneity test proves whether there was statistical significance in the differences in effect size, study quality, sample content between studies. The heterogeneity test (P ≥ 0.05) was a fixed effect model, and the random effect model was selected when p < 0.05. After determining the model, the inverse variance method was selected to merge the effect values included in the trial. The standard mean difference (SMD) was used to measure the effect value, and the combined effect value was shown in the forest chart. Excluding the literature with high risk of bias control, sensitivity analysis was performed to re estimate the combined effect value, and compared with the results of meta-analysis before exclusion. Funnel plot and egger test were used to understand the potential publication bias. Results Included literature and quality evaluation Included literature A total of 1225 Chinese and English literature articles were obtained from the database according to the search terms. 600 duplicate literature articles were removed by EndNote X9 software, and 625 articles were obtained for abstract and title screening. After 500 articles were removed, the full text was carefully read, and 6 articles were included for Meta analysis. Figure 1 . Basic characteristics of the references included in the study The meta-analysis included six randomized controlled clinical trials, published between 1988 and 2020, involving 1,741 children, 868 of whom were given vitamin D supplementation and 873 of whom were given placebo. The children were between the ages of 5 and 16 years, and the duration of the vitamin D supplement intervention was between 12 and 96 weeks. Vitamin D supplementation is given in doses of vitamin D between 932 and 30,00IU per week. Table 1 . Table 1 Basic characteristics included in meta-analysis Included references Country Number of cases Age Gender Female/male Vitamin D Intervention measure Duration of intervention (week) Outcome E C E C E C E(IU/week) C Davaasambuu Ganmaa 2012[ 8 ] USA 61 59 13.0 6 ± 1.1 13.1 6 ± 1.5 33/28 28/31 5600 placebo 24 1,2,4 D. B. D. L. Samaranayake 2020[ 9 ] Sri Lanka 32 31 9.95 ± 2.02 10.61 ± 1.83 10/22 6/25 50000 placebo 12 1,3 Geeta Trilok-Kumar 2015[ 10 ] India 446 466 5.0 ± 1.0 5.0 ± 1.0 227/219 248/218 1400 placebo 96 2,3,4,5 Michał Brzeziński 2020 [ 13 ] Poland 85 67 11.10 ± 2.84 10.70 ± 3.13 46/39 38/29 1200 placebo 26 1,2,3 Neil R Brett 2018[ 14 ] Canada 26 25 5.4 ± 2.0 5.0 ± 1.8 14/12 10/15 2800 placebo 24 1,2,4,5 Roya Kelishadia 2014[ 15 ] Iran 21 22 10–16 10–16 - - 300,000 placebo 12 1,2 Note: Group E was the observation group and was given vitamin D supplement. Group C was the control group and was given placebo. 1 is the level of serum 25(OH)D3. 2 is BMI; 3 is the relative fat index, 4 is height and 5 is weight. Results of literature quality assessment We used the Cochrane Collaboration's bias risk assessment tool to assess the risk of publication bias and found that the risk of bias was generally low for all studies included in the analysis. Of these studies, 100% (6/6) explicitly used random-number table grouping without selection bias, 1 study was at high risk of assignment hiding, most of the others did not state whether assignment hiding was or not, blinded participants and staff, and whether results were evaluated. In all cases, no risk was identified. Figure 2 . Meta-analysis of clinical results Serum 25(OH)D3 levels Four studies involving serum 25(OH)D3 level outcomes included 603 children, 308 of whom were given vitamin D supplementation and 295 of whom were given placebo. After the heterogeneity test, P < 0.00001, I2 = 90%, indicating high heterogeneity, so the random effects combined model was used for analysis, and the results showed that compared with the placebo group, Vitamin D supplementation can significantly increase serum 25(OH)D3 levels in children [n = 603, mean difference (MD) = 5.08 ng/ml, 95%CI (0.57,9.60), P = 0.03]. Figure 3 . BMI In five studies involving BMI outcomes, a total of 1,514 children were enrolled, including 752 in the vitamin D supplement group and 762 in the placebo group. After the heterogeneity test, P = 0.07, I2 = 53%, indicating the existence of high heterogeneity, so the random effects combined model was used for analysis. The results showed that, There was no significant difference in BMI between the placebo and vitamin D supplementation groups [n = 1514, MD=-0,08 kg/m2, 95%CI (-0.47,0.30), P = 0.67]. Figure 4 . Relative fat index In four studies involving relative adipose-level outcome measures, a total of 1127 children were enrolled, including 563 in the vitamin D supplement group and 564 in the placebo group. After the heterogeneity test, P < 0.00001, I2 = 100%, indicating the existence of high heterogeneity, so the random effects combined model was used for analysis. The results showed that, There was no significant difference in relative fat index between placebo and vitamin D supplementation groups [n = 1127, MD =-0.88%, 95%CI (-26.24,24.47), P = 0.95]. Figure 5 . Height In four studies involving height outcome measures, a total of 1426 children were enrolled, including 701 in the vitamin D supplement group and 725 in the placebo group. After the heterogeneity test, P = 0.51, I2 = 0%, indicating low heterogeneity, fixed effect model was adopted for analysis, and there was no significant difference in height between the placebo group and the vitamin D supplement group [n = 1426, MD = 0.18cm, 95%CI (-0.61,0.97), P = 0.66]. Figure 6 . Weight Our four studies involved a total of 1426 children on weight outcome measures, including 701 in the vitamin D supplement group and 725 in the placebo group. After the heterogeneity test, P = 0.46, I2 = 0%, indicating low heterogeneity, fixed-effect model was adopted for analysis, and there was no significant difference in body weight between the placebo group and the vitamin D supplement group [n = 1426, MD =-0.10 kg, 95%CI (-0.43,0.22), P = 0.53]. Figure 7 . Discussion In the realm of pediatric health, the role of vitamin D has been a subject of intense research and scrutiny. This meta-analysis endeavors to delve deep into the effects of vitamin D supplementation on various aspects of children's growth and development, offering valuable insights and a consolidated understanding of this crucial topic. The primary finding of our meta-analysis reveals that vitamin D supplementation significantly elevates the serum 25(OH)D3 levels in children [ 15 ]. This is a critical outcome as adequate serum 25(OH)D is indispensable for optimal bone health in the growing years. The Institute of Medicine has stipulated that a serum 25(OH)D concentration ranging between 50 and 125 nmol/L is conducive to healthy bone development in children [ 16 ]. Our study indicates that a daily dose of 400 IU of vitamin D initially ensures that 100% of children maintain a serum 25(OH)D level above 40 nmol/L [ 17 ]. Nevertheless, as the intervention duration extends, an escalation in the dosage might be necessary to sustain this threshold. This could potentially be attributed to seasonal variations [ 18 ], where sunlight exposure and thus endogenous vitamin D synthesis fluctuate, or it could be due to the progressive growth and changing physiological needs of the child [ 19 ]. For instance, in children younger than 11 years, the average serum 25(OH)D levels typically range from 64 to 69 nmol/L [ 20 ], while for those aged 4–17 years, the average in the autumn season is approximately 72.8 nmol/L [ 21 ]. Moreover, it is notable that children with higher BMI tend to have a greater demand for serum 25(OH)D [ 22 ]. Our meta-analysis further substantiates that a weekly supplementation of 932 IU of vitamin D effectively maintains the serum levels above 40 nmol/L, presenting a statistically significant difference when compared to the control group [ 23 ]. Turning our attention to the impact of vitamin D on children's physical growth, particularly height, our analysis reveals no significant enhancement [ 24 ]. This finding aligns with the results of a previous meta-analysis [ 25 ], reinforcing the consistency of this observation across multiple studies. The mechanism through which vitamin D influences growth remains somewhat enigmatic. However, emerging research suggests a potential link between vitamin D and the GH/IGF-1 axis, which might provide some clues to its modulatory effects on growth [ 26 ]. Vitamin D is hypothesized to augment the secretion of IGF-1 and its binding protein (IGFBP-3) in the liver and enhance the expression of IGF-1 receptors in diverse tissues [ 27 ]. Some studies have postulated that vitamin D could stimulate the secretion of growth hormone, concurrently with an increase in weight and height [ 28 ]. Intriguingly, in our current meta-analysis, despite the supplementation, no substantial change was noted in height. When it comes to body mass index (BMI), although there is a discernible downward trend following vitamin D supplementation compared to the control group, suggesting a reduction in the weight-to-height-squared ratio, it is speculated that weight is a key determinant influencing the BMI index. A separate investigation focused on the effects of vitamin D supplementation in low-weight infants has yielded mixed results. While three studies suggest that a 6-month vitamin D supplementation regimen improves the weight-for-age Z-score and height-for-age Z-score of infants [ 29 ], a significant number of 14 clinical trials indicate that vitamin D supplementation has no discernible impact on overall growth in children, except for its influence on parathyroid hormone and serum 25(OH)D levels [ 30 ]. Limitations The present meta-analysis, while providing valuable insights into the effects of vitamin D supplementation on children's growth and development, is not without its limitations and shortcomings. One of the primary limitations lies in the heterogeneity of the included studies. The studies varied in terms of the dosage, duration, and frequency of vitamin D supplementation, as well as the characteristics of the study populations, such as age, baseline vitamin D status, and overall health. This heterogeneity makes it challenging to draw definitive and uniform conclusions. The measurement methods of the outcome variables also presented inconsistencies. Different studies employed diverse techniques to assess serum 25(OH)D levels, BMI, height, and other parameters, introducing potential measurement errors and variations in the reported results. Furthermore, the long-term effects of vitamin D supplementation on children's growth and development were not comprehensively evaluated. Our analysis focused on a relatively short-term period, and the potential cumulative or delayed effects over an extended duration remain unknown. Another significant limitation is the lack of detailed information on the children's lifestyles and environmental factors. Factors such as physical activity levels, dietary habits, and exposure to sunlight, which can independently influence vitamin D status and growth, were not consistently accounted for in the included studies. Recommendations Looking ahead to the future, several prospects and recommendations emerge to enhance our understanding and management of vitamin D's role in children's health. Firstly, future studies should aim for greater homogeneity in study design. This includes standardizing the dosage, duration, and frequency of vitamin D supplementation, as well as establishing uniform methods for outcome measurements. This will enable more accurate comparisons and meta-analyses. Secondly, long-term follow-up studies are essential to comprehensively assess the sustained effects of vitamin D supplementation on children's growth and development. These studies should extend over several years to capture potential changes that may manifest over time. In addition, a more comprehensive assessment of children's lifestyles and environmental factors should be incorporated. This could involve detailed questionnaires or objective measures of physical activity, dietary intake, and sunlight exposure to better account for confounding variables. Furthermore, mechanistic studies are needed to elucidate the exact molecular and cellular pathways through which vitamin D influences growth and development. This will provide a deeper understanding of the underlying processes and potentially identify novel therapeutic targets. Conclusion In conclusion, while this meta-analysis has advanced our knowledge, it also highlights the areas that require further research and improvement. Addressing these limitations and following the proposed recommendations will undoubtedly contribute to a more comprehensive and precise understanding of the role of vitamin D in children's growth and development. Declarations Author Contribution I am the sole author of this work. There was no Funding. Clinical trial number: not applicable. 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song","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBElEQVRIie3RMWrDMBSAYT0E9iLHq4QhvcIDQ6bSXKUi4MlDj6BgkJcYOiZD79AubUYbgbu4u8dCwFOWLKUBD7WhW2u73TLoHwR68CEhEWKzXWA+hfQTFL/x3aT8nt2OE5EmioO6XolNGXV7nCZYvfYkgsc6XvyNkFqq0Nsbinn8cWBtS3w3RnLeDwvYSiV3lZmJ/O0l9DQSsTkiZNUwoVyq/KQNnRXZc+ApJFjHSEEPE4fLtZLagDKsCViLZDlFGCsSctIR3JfMCZjTncInCHfXGna6f2RnIR50yHjV3BXZCFkat6Ge7r7y6tDwYzuf++nq6f08Qn7etF/yfwCbzWaz/dIXGZRSlLsYuwgAAAAASUVORK5CYII=","orcid":"","institution":"Wuhan Union Hospital","correspondingAuthor":true,"prefix":"","firstName":"tiantian","middleName":"","lastName":"song","suffix":""}],"badges":[],"createdAt":"2025-06-06 02:38:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6832894/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6832894/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85171977,"identity":"2a82c052-bc51-485f-b85b-fa610342d8ce","added_by":"auto","created_at":"2025-06-23 05:48:41","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":109218,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA 2020 flow diagram for new systematic reviews\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6832894/v1/62d936c9243994b49d0287aa.jpeg"},{"id":85171975,"identity":"c99fb8eb-6a55-4a5f-86bc-3cafb15ddf67","added_by":"auto","created_at":"2025-06-23 05:48:41","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":8143,"visible":true,"origin":"","legend":"\u003cp\u003eInclusion of research bias risk studies\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6832894/v1/524dc0da8362c5fd7be75249.png"},{"id":85173220,"identity":"4a71b570-37f8-4e18-a661-9cb92e6d1429","added_by":"auto","created_at":"2025-06-23 05:56:42","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":10607,"visible":true,"origin":"","legend":"\u003cp\u003eForest map comparison of serum 25(OH)D3 levels\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6832894/v1/05daf9415ba04bbda58e9e94.png"},{"id":85171981,"identity":"bd127bea-dcb4-4cbc-a808-236ca67198cf","added_by":"auto","created_at":"2025-06-23 05:48:41","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":11112,"visible":true,"origin":"","legend":"\u003cp\u003eForest map comparison of BMI\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6832894/v1/7dd8b5141e3599d74a1e853b.png"},{"id":85173216,"identity":"9ae9f3f1-70e9-4e7f-8560-874510633839","added_by":"auto","created_at":"2025-06-23 05:56:41","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":10341,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of forest plots with relative adipose index\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-6832894/v1/d99e77e49d71d98fa0b0d373.png"},{"id":85171976,"identity":"2e906cd7-46da-4436-9a15-634cdc16ebdf","added_by":"auto","created_at":"2025-06-23 05:48:41","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":10893,"visible":true,"origin":"","legend":"\u003cp\u003eForest map comparison of height\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-6832894/v1/f8eb9770fb60a39bd40f7203.png"},{"id":85171988,"identity":"a76ef1f5-e165-4237-9441-89ad96f15455","added_by":"auto","created_at":"2025-06-23 05:48:41","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":10802,"visible":true,"origin":"","legend":"\u003cp\u003eForest map comparison of body weight\u003c/p\u003e","description":"","filename":"floatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-6832894/v1/d3d7d046214b604cd31e2833.png"},{"id":99795365,"identity":"6992408d-f6b5-4c53-9e97-be2beebb7eda","added_by":"auto","created_at":"2026-01-08 13:37:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":837092,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6832894/v1/1d2318f6-06be-4feb-bb25-6529ebccb830.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Meta-analysis of the effects of vitamin D on growth, development and body weight of children of different ages","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNutrient deficiency is an important factor affecting children\u0026rsquo;s growth and development. Many studies showed that the dietary structure of many children was unreasonable, resulting in insufficient intake of calcium, vitamin D and other nutrients [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Children\u0026rsquo;s long-term lack of calcium, vitamin D and other nutrients could lead to growth retardation [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Vitamin D can effectively promote calcium absorption, participate in bone formation, and help promote children\u0026rsquo;s bone development [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Vitamin D is essential nutrients for human growth and development, especially for the development of fetuses and infants [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Vitamin D is a trace element that promotes children\u0026rsquo;s healthy growth. It plays a major role in promoting calcium absorption and ensuring bone strength. It also plays an important role in the prevention of many diseases in adulthood [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Vitamin D can increase the absorption of calcium by the body, and has a positive role in promoting the growth and development of children. Moreover, vitamin D has an important regulatory function on the immune function of the human body [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eVitamin D deficiency has been linked to a number of health problems in children and adolescents, including an increased risk of rickets, asthma, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, infections, and type 1 diabetes. Vitamin D supplementation has also been shown to have a beneficial effect in preventing and/or ameliorating most of these diseases [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Childhood overweight and obesity remain a major health problem worldwide. A meta-analysis showed that body weight/fat mass was inversely associated with vitamin D status in the general population and in children [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The association between vitamin D supplementation and body weight weakens with age and has a significant impact on the height and weight of growing children [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, the results of different randomized controlled clinical trials have shown that vitamin D supplementation may increase body weight and reduce fat mass in children, but some studies have not found significant effects. However, most of the studies have shortcomings such as small sample size, uneven reliability and inconsistent baseline, which leaded to divergent conclusions and lack of uniform clinical standards. Therefore, this study summarizes the effects of vitamin D on children\u0026rsquo;s growth and development based on meta-analysis.\u003c/p\u003e"},{"header":"Material and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eLiterature search method\u003c/h2\u003e \u003cp\u003eWe searched PubMed, EMBASE and Cochrane Library as search databases, and collected RCT studies on vitamin D. The search period was from January 2000 to June 2023. The search was carried out by combining subject words with free words, and the references included in the research topic were searched. The key words included vitamin D, children\u0026rsquo;s growth and development. Manual retrieval of relevant journals and retrospective search of references for relevant research.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eLiterature inclusion and exclusion criteria\u003c/h3\u003e\n\u003cp\u003e \u003cb\u003eInclusion criteria\u003c/b\u003e: The language of the literature was English. The publication period was from 2000 to June 2022. The research method was a randomized controlled trial (RCT), and the results reported the changes of height and weight after the intervention. The intervention subjects were children aged 0\u0026ndash;14 years, and the intervention time was more than 8 weeks. \u003cb\u003eExclusion criteria\u003c/b\u003e: Papers with duplicate contents; unable to extract analysis data; the type of study was non randomized trial, and there was not enough data to calculate the change value; the included subjects had chronic diseases affecting growth and development, such as protein energy malnutrition and anemia.\u003c/p\u003e\n\u003ch3\u003eLiterature screening and excerpts\u003c/h3\u003e\n\u003cp\u003eIn combination with the literature search results, read through the literature that may be related to this study according to the title and abstract, and screen according to the inclusion criteria and exclusion criteria. After discussion, it was decided to add the research literature that meets the criteria in the reading. Establish an information extraction table, including country, author, title, publication years, article source, research object, inclusion criteria, age, number of people, intervention time. The extracted information was a blind method, which was implemented independently by two persons. At least three persons with different opinions discuss and combine the opinions of third-party experts.\u003c/p\u003e\n\u003ch3\u003eDocument quality\u003c/h3\u003e\n\u003cp\u003eIn combination with the risk bias assessment method published in the Cochrane manual (2011 Edition), the quality of the included literature was evaluated. The contents include selection bias, implementation bias, measurement bias, follow-up bias and reporting bias.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eRevman5.2 software was selected. The heterogeneity test proves whether there was statistical significance in the differences in effect size, study quality, sample content between studies. The heterogeneity test (P\u0026thinsp;\u0026ge;\u0026thinsp;0.05) was a fixed effect model, and the random effect model was selected when p \u0026lt; 0.05. After determining the model, the inverse variance method was selected to merge the effect values included in the trial. The standard mean difference (SMD) was used to measure the effect value, and the combined effect value was shown in the forest chart. Excluding the literature with high risk of bias control, sensitivity analysis was performed to re estimate the combined effect value, and compared with the results of meta-analysis before exclusion. Funnel plot and egger test were used to understand the potential publication bias.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eIncluded literature and quality evaluation\u003c/h2\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003eIncluded literature\u003c/h2\u003e \u003cp\u003eA total of 1225 Chinese and English literature articles were obtained from the database according to the search terms. 600 duplicate literature articles were removed by EndNote X9 software, and 625 articles were obtained for abstract and title screening. After 500 articles were removed, the full text was carefully read, and 6 articles were included for Meta analysis. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eBasic characteristics of the references included in the study\u003c/h2\u003e \u003cp\u003eThe meta-analysis included six randomized controlled clinical trials, published between 1988 and 2020, involving 1,741 children, 868 of whom were given vitamin D supplementation and 873 of whom were given placebo. The children were between the ages of 5 and 16 years, and the duration of the vitamin D supplement intervention was between 12 and 96 weeks. Vitamin D supplementation is given in doses of vitamin D between 932 and 30,00IU per week. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBasic characteristics included in meta-analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"12\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIncluded references\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCountry\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eNumber of cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eGender Female/male\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003eVitamin D Intervention measure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDuration of intervention (week)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eE(IU/week)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eC\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDavaasambuu Ganmaa 2012[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.0 6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13.1 6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e33/28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e28/31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e5600\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eplacebo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e1,2,4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD. B. D. L. Samaranayake 2020[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSri Lanka\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.95\u0026thinsp;\u0026plusmn;\u0026thinsp;2.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.61\u0026thinsp;\u0026plusmn;\u0026thinsp;1.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10/22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6/25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e50000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eplacebo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e1,3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeeta Trilok-Kumar 2015[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e446\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e466\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e227/219\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e248/218\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eplacebo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e2,3,4,5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMichał Brzeziński 2020 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePoland\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.10\u0026thinsp;\u0026plusmn;\u0026thinsp;2.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.70\u0026thinsp;\u0026plusmn;\u0026thinsp;3.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e46/39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e38/29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eplacebo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e1,2,3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeil R Brett 2018[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCanada\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e14/12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10/15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2800\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eplacebo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e1,2,4,5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRoya Kelishadia 2014[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIran\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u0026ndash;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10\u0026ndash;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e300,000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eplacebo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e1,2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eNote: Group E was the observation group and was given vitamin D supplement. Group C was the control group and was given placebo. 1 is the level of serum 25(OH)D3. 2 is BMI; 3 is the relative fat index, 4 is height and 5 is weight.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eResults of literature quality assessment\u003c/h2\u003e \u003cp\u003eWe used the Cochrane Collaboration's bias risk assessment tool to assess the risk of publication bias and found that the risk of bias was generally low for all studies included in the analysis. Of these studies, 100% (6/6) explicitly used random-number table grouping without selection bias, 1 study was at high risk of assignment hiding, most of the others did not state whether assignment hiding was or not, blinded participants and staff, and whether results were evaluated. In all cases, no risk was identified. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eMeta-analysis of clinical results\u003c/h2\u003e \u003cdiv id=\"Sec14\" class=\"Section3\"\u003e \u003ch2\u003eSerum 25(OH)D3 levels\u003c/h2\u003e \u003cp\u003eFour studies involving serum 25(OH)D3 level outcomes included 603 children, 308 of whom were given vitamin D supplementation and 295 of whom were given placebo. After the heterogeneity test, P\u0026thinsp;\u0026lt;\u0026thinsp;0.00001, I2\u0026thinsp;=\u0026thinsp;90%, indicating high heterogeneity, so the random effects combined model was used for analysis, and the results showed that compared with the placebo group, Vitamin D supplementation can significantly increase serum 25(OH)D3 levels in children [n\u0026thinsp;=\u0026thinsp;603, mean difference (MD)\u0026thinsp;=\u0026thinsp;5.08 ng/ml, 95%CI (0.57,9.60), P\u0026thinsp;=\u0026thinsp;0.03]. Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eBMI\u003c/h2\u003e \u003cp\u003eIn five studies involving BMI outcomes, a total of 1,514 children were enrolled, including 752 in the vitamin D supplement group and 762 in the placebo group. After the heterogeneity test, P\u0026thinsp;=\u0026thinsp;0.07, I2\u0026thinsp;=\u0026thinsp;53%, indicating the existence of high heterogeneity, so the random effects combined model was used for analysis. The results showed that, There was no significant difference in BMI between the placebo and vitamin D supplementation groups [n\u0026thinsp;=\u0026thinsp;1514, MD=-0,08 kg/m2, 95%CI (-0.47,0.30), P\u0026thinsp;=\u0026thinsp;0.67]. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eRelative fat index\u003c/h2\u003e \u003cp\u003eIn four studies involving relative adipose-level outcome measures, a total of 1127 children were enrolled, including 563 in the vitamin D supplement group and 564 in the placebo group. After the heterogeneity test, P\u0026thinsp;\u0026lt;\u0026thinsp;0.00001, I2\u0026thinsp;=\u0026thinsp;100%, indicating the existence of high heterogeneity, so the random effects combined model was used for analysis. The results showed that, There was no significant difference in relative fat index between placebo and vitamin D supplementation groups [n\u0026thinsp;=\u0026thinsp;1127, MD =-0.88%, 95%CI (-26.24,24.47), P\u0026thinsp;=\u0026thinsp;0.95]. Figure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eHeight\u003c/h2\u003e \u003cp\u003eIn four studies involving height outcome measures, a total of 1426 children were enrolled, including 701 in the vitamin D supplement group and 725 in the placebo group. After the heterogeneity test, P\u0026thinsp;=\u0026thinsp;0.51, I2\u0026thinsp;=\u0026thinsp;0%, indicating low heterogeneity, fixed effect model was adopted for analysis, and there was no significant difference in height between the placebo group and the vitamin D supplement group [n\u0026thinsp;=\u0026thinsp;1426, MD\u0026thinsp;=\u0026thinsp;0.18cm, 95%CI (-0.61,0.97), P\u0026thinsp;=\u0026thinsp;0.66]. Figure\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eWeight\u003c/h2\u003e \u003cp\u003eOur four studies involved a total of 1426 children on weight outcome measures, including 701 in the vitamin D supplement group and 725 in the placebo group. After the heterogeneity test, P\u0026thinsp;=\u0026thinsp;0.46, I2\u0026thinsp;=\u0026thinsp;0%, indicating low heterogeneity, fixed-effect model was adopted for analysis, and there was no significant difference in body weight between the placebo group and the vitamin D supplement group [n\u0026thinsp;=\u0026thinsp;1426, MD =-0.10 kg, 95%CI (-0.43,0.22), P\u0026thinsp;=\u0026thinsp;0.53]. Figure\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the realm of pediatric health, the role of vitamin D has been a subject of intense research and scrutiny. This meta-analysis endeavors to delve deep into the effects of vitamin D supplementation on various aspects of children's growth and development, offering valuable insights and a consolidated understanding of this crucial topic. The primary finding of our meta-analysis reveals that vitamin D supplementation significantly elevates the serum 25(OH)D3 levels in children [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. This is a critical outcome as adequate serum 25(OH)D is indispensable for optimal bone health in the growing years. The Institute of Medicine has stipulated that a serum 25(OH)D concentration ranging between 50 and 125 nmol/L is conducive to healthy bone development in children [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Our study indicates that a daily dose of 400 IU of vitamin D initially ensures that 100% of children maintain a serum 25(OH)D level above 40 nmol/L [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Nevertheless, as the intervention duration extends, an escalation in the dosage might be necessary to sustain this threshold. This could potentially be attributed to seasonal variations [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], where sunlight exposure and thus endogenous vitamin D synthesis fluctuate, or it could be due to the progressive growth and changing physiological needs of the child [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. For instance, in children younger than 11 years, the average serum 25(OH)D levels typically range from 64 to 69 nmol/L [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], while for those aged 4\u0026ndash;17 years, the average in the autumn season is approximately 72.8 nmol/L [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Moreover, it is notable that children with higher BMI tend to have a greater demand for serum 25(OH)D [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Our meta-analysis further substantiates that a weekly supplementation of 932 IU of vitamin D effectively maintains the serum levels above 40 nmol/L, presenting a statistically significant difference when compared to the control group [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTurning our attention to the impact of vitamin D on children's physical growth, particularly height, our analysis reveals no significant enhancement [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. This finding aligns with the results of a previous meta-analysis [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], reinforcing the consistency of this observation across multiple studies. The mechanism through which vitamin D influences growth remains somewhat enigmatic. However, emerging research suggests a potential link between vitamin D and the GH/IGF-1 axis, which might provide some clues to its modulatory effects on growth [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Vitamin D is hypothesized to augment the secretion of IGF-1 and its binding protein (IGFBP-3) in the liver and enhance the expression of IGF-1 receptors in diverse tissues [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Some studies have postulated that vitamin D could stimulate the secretion of growth hormone, concurrently with an increase in weight and height [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Intriguingly, in our current meta-analysis, despite the supplementation, no substantial change was noted in height.\u003c/p\u003e \u003cp\u003eWhen it comes to body mass index (BMI), although there is a discernible downward trend following vitamin D supplementation compared to the control group, suggesting a reduction in the weight-to-height-squared ratio, it is speculated that weight is a key determinant influencing the BMI index. A separate investigation focused on the effects of vitamin D supplementation in low-weight infants has yielded mixed results. While three studies suggest that a 6-month vitamin D supplementation regimen improves the weight-for-age Z-score and height-for-age Z-score of infants [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], a significant number of 14 clinical trials indicate that vitamin D supplementation has no discernible impact on overall growth in children, except for its influence on parathyroid hormone and serum 25(OH)D levels [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThe present meta-analysis, while providing valuable insights into the effects of vitamin D supplementation on children's growth and development, is not without its limitations and shortcomings.\u003c/p\u003e \u003cp\u003eOne of the primary limitations lies in the heterogeneity of the included studies. The studies varied in terms of the dosage, duration, and frequency of vitamin D supplementation, as well as the characteristics of the study populations, such as age, baseline vitamin D status, and overall health. This heterogeneity makes it challenging to draw definitive and uniform conclusions.\u003c/p\u003e \u003cp\u003eThe measurement methods of the outcome variables also presented inconsistencies. Different studies employed diverse techniques to assess serum 25(OH)D levels, BMI, height, and other parameters, introducing potential measurement errors and variations in the reported results.\u003c/p\u003e \u003cp\u003eFurthermore, the long-term effects of vitamin D supplementation on children's growth and development were not comprehensively evaluated. Our analysis focused on a relatively short-term period, and the potential cumulative or delayed effects over an extended duration remain unknown.\u003c/p\u003e \u003cp\u003eAnother significant limitation is the lack of detailed information on the children's lifestyles and environmental factors. Factors such as physical activity levels, dietary habits, and exposure to sunlight, which can independently influence vitamin D status and growth, were not consistently accounted for in the included studies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eRecommendations\u003c/h2\u003e \u003cp\u003eLooking ahead to the future, several prospects and recommendations emerge to enhance our understanding and management of vitamin D's role in children's health. Firstly, future studies should aim for greater homogeneity in study design. This includes standardizing the dosage, duration, and frequency of vitamin D supplementation, as well as establishing uniform methods for outcome measurements. This will enable more accurate comparisons and meta-analyses. Secondly, long-term follow-up studies are essential to comprehensively assess the sustained effects of vitamin D supplementation on children's growth and development. These studies should extend over several years to capture potential changes that may manifest over time. In addition, a more comprehensive assessment of children's lifestyles and environmental factors should be incorporated. This could involve detailed questionnaires or objective measures of physical activity, dietary intake, and sunlight exposure to better account for confounding variables. Furthermore, mechanistic studies are needed to elucidate the exact molecular and cellular pathways through which vitamin D influences growth and development. This will provide a deeper understanding of the underlying processes and potentially identify novel therapeutic targets.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, while this meta-analysis has advanced our knowledge, it also highlights the areas that require further research and improvement. Addressing these limitations and following the proposed recommendations will undoubtedly contribute to a more comprehensive and precise understanding of the role of vitamin D in children's growth and development.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eI am the sole author of this work.\u003c/p\u003e\u003cp\u003eThere was no Funding.\u003c/p\u003e\n\u003cp\u003eClinical trial number: not applicable.\u003c/p\u003e\n\u003cp\u003eEthics, Consent to Participate, and Consent to Publish declarations: not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDeruyter S, Van Biervliet S, De Guchtenaere A. Response to vitamin D replacement therapy in obese children and adolescents with vitamin D deficiency: a randomized controlled trial. J Pediatr Endocrinol metabolism: JPEM. 2023;36:458\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFlores-Aldana M, Rivera-Pasquel M, Garc\u0026iacute;a-Guerra A, P\u0026eacute;rez-Cort\u0026eacute;s JG, B\u0026aacute;rcena-Echegoll\u0026eacute;n JE. Effect of Vitamin D Supplementation on (25(OH)D) Status in Children 12\u0026ndash;30 Months of Age. Nutrients: A Randomized Clinical Trial; 2023. p. 15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGanmaa D, Khudyakov P, Buyanjargal U, Tserenkhuu E, Erdenenbaatar S, Achtai CE, Yansanjav N, Delgererekh B, Ankhbat M, Tsendjav E, Ochirbat B, Jargalsaikhan B, Enkhmaa D, Martineau AR. Vitamin D supplements for fracture prevention in schoolchildren in Mongolia: analysis of secondary outcomes from a multicentre, double-blind, randomised, placebo-controlled trial, The lancet. 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Am J Clin Nutr. 2006;83:714\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAla-Houhala M, Koskinen T, Koskinen M, Visakorpi JK. Double blind study on the need for vitamin D supplementation in prepubertal children. Acta Paediatr Scand. 1988;77:89\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrzeziński M, Jankowska A, Słomińska-Frączek M, Metelska P, Wiśniewski P, Socha P, Szlagatys-Sidorkiewicz A. Long-Term Effects of Vitamin D Supplementation in Obese Children During Integrated Weight-Loss Programme-A Double Blind Randomized Placebo-Controlled Trial. Nutrients. 2020;12(4):1093.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrett NR, Parks CA, Lavery P, Agellon S, Vanstone CA, Kaufmann M, Jones G, Maguire JL, Rauch F, Weiler HA. Vitamin D status and functional health outcomes in children aged 2\u0026ndash;8 y: a 6-mo vitamin D randomized controlled trial. 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Schizophr Res. 2022;247:16\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVivanti AJ, Monier I, Salakos E, Elie C, Tsatsaris V, Senat MV, Jani J, Jouannic JM, Winer N, Zeitlin J, Mougneaud C, Souberbielle JC, Courbebaisse M, Benachi A. Vitamin D and pregnancy outcomes: Overall results of the FEPED study. J Gynecol Obstet Hum Reprod. 2020;49(8):101883.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNeufingerl N, Eilander A. Nutrient Intake and Status in Children and Adolescents Consuming Plant-Based Diets Compared to Meat-Eaters: A Systematic Review. Nutrients. 2023;15(20):4341.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBeauchesne AR, Cara KC, Krobath DM, Penkert LP, Shertukde SP, Cahoon DS, Prado B, Li R, Yao Q, Huang J, Reh T, Chung M. Vitamin D intakes and health outcomes in infants and preschool children: Summary of an evidence report. Ann Med. 2022;54(1):2278\u0026ndash;301.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Vitamin D, Children, Growth and development, Meta analysis","lastPublishedDoi":"10.21203/rs.3.rs-6832894/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6832894/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eDue to the rapid growth and development of children, they were easily affected by various bad living habits and other factors, resulting in insufficient intake of one or more nutrients. Vitamin D drops could effectively promote children\u0026rsquo;s growth and development, but there was no comprehensive analysis of the effects of vitamin D drops on children\u0026rsquo;s growth and development. We want to systematically evaluate the effects of vitamin D drops on different ages of children\u0026rsquo;s growth and development by meta-analysis.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePubMed, EMBASE and Cochrane Library as search databases was collected from January 2000 to June 2023. The randomized controlled trials (RCTs) on the effects of vitamin D on children\u0026rsquo;s growth and development were searched, the literatures were screened, the data (height and weight) were extracted, and the risk of bias in the included studies was evaluated. The meta-analysis was conducted using Stata. 11 software.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eWe included six studies, all randomized controlled trials of the effects of vitamin D supplementation on growth and development in children. The results showed that compared with the placebo group in the control group, vitamin D supplementation could significantly improve the level of serum 25(OH)D3 in children [n\u0026thinsp;=\u0026thinsp;603, mean difference (MD)\u0026thinsp;=\u0026thinsp;5.08 ng/ml, 95%CI (0.57,9.60), P\u0026thinsp;=\u0026thinsp;0.03]. BMI, height, body weight and relative fat index had little effect, and there was no significant comparison between groups, which were [n\u0026thinsp;=\u0026thinsp;1514, MD=-0,08 kg/m2, 95%CI (-0.47,0.30), P\u0026thinsp;=\u0026thinsp;0.67], respectively. [n\u0026thinsp;=\u0026thinsp;1426, MD\u0026thinsp;=\u0026thinsp;0.18 cm, 95% CI (0.61, 0.97), P\u0026thinsp;=\u0026thinsp;0.66). (n\u0026thinsp;=\u0026thinsp;1426, MD\u0026thinsp;=\u0026thinsp;0.10 kg, 95% CI (0.43, 0.22), P\u0026thinsp;=\u0026thinsp;0.53) and (n\u0026thinsp;=\u0026thinsp;1127, MD\u0026thinsp;=\u0026thinsp;0.88%, 95% CI (26.24, 24.47), P\u0026thinsp;=\u0026thinsp;0.95).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe study suggests that while vitamin D supplementation effectively boosts serum 25(OH)D3 levels in children, it has limited influence on other growth and development parameters such as BMI, height, body weight, and relative fat index.\u003c/p\u003e","manuscriptTitle":"Meta-analysis of the effects of vitamin D on growth, development and body weight of children of different ages","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-23 05:48:36","doi":"10.21203/rs.3.rs-6832894/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6cbcdf6c-1e7e-44ac-9cca-8743f78fbb87","owner":[],"postedDate":"June 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-07T03:09:09+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-23 05:48:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6832894","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6832894","identity":"rs-6832894","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}