Abstract
Background
Acute respiratory infections (ARIs) remain a leading cause of morbidity and mortality in pediatric populations worldwide. Vitamin D has immunomodulatory functions that may influence susceptibility and outcomes of respiratory infections, yet trial results in pediatric populations remain inconsistent.
Methods
A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted in accordance with PRISMA guidelines. MEDLINE, Embase, Web of Science, and Cochrane Library were searched through April 2025. Eligible RCTs enrolled pediatric populations, comparing oral vitamin D supplementation with placebo or no treatment, and reported ARI-related outcomes. Pooled risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated using random- or fixed-effects models.
Results
Seventeen RCTs including 18,372 participants were analyzed. Overall, vitamin D supplementation did not significantly reduce ARI incidence (RR = 0.82, 95% CI: 0.64 to 1.06), hospitalization duration (MD = 0.03 days, 95% CI: -0.72 to 0.78), recovery time (MD = -4.36 h, 95% CI: -11.87 to 3.15), or all-cause mortality (RR = 0.88, 95% CI: 0.60 to 1.28). Subgroup analysis showed preventive benefit with daily low-dose regimens (≤ 1000 IU/day; RR = 0.42, 95% CI: 0.27 to 0.66), but not with higher doses. Supplementation was associated with fewer serious adverse events (RR = 0.83, 95% CI: 0.71 to 0.96).
Conclusion
Vitamin D supplementation cannot be recommended as a universal intervention for childhood ARIs. Preventive efficacy may be achieved with daily low-dose regimens, but supplementation does not improve clinical outcomes once infection occurs. Vitamin D appears safe, and further high-quality pediatric trials are warranted to define optimal dosing strategies.
Trial registration
CRD420251133291.
Keywords: Vitamin d, Acute respiratory infections, Pediatric populations, Meta analysis, Randomized controlled trials
Introduction
Acute respiratory infections (ARIs) remain among the leading causes of morbidity and mortality in pediatric populations worldwide. According to the Global Burden of Disease 2019 study, lower respiratory infections were still a leading cause of under-five mortality in 2019, contributing substantially to the global burden despite improvements achieved in recent decades [1]. Although vaccines and antimicrobial therapies have reduced mortality in some settings, the overall incidence and severity of ARIs remain high, particularly in low- and middle-income countries, underscoring the need for complementary preventive and therapeutic approaches [2].
Beyond its well-established role in skeletal health, vitamin D has immunomodulatory functions relevant to respiratory infection. Its active metabolite enhances innate immune responses, stimulates antimicrobial peptide production, and modulates inflammatory pathways [3]. Observational research in children and adolescents has linked lower circulating 25-hydroxyvitamin D concentrations with increased susceptibility to and severity of respiratory infections, providing biological plausibility for supplementation as a preventive or adjunctive therapeutic approach [4, 5].
Findings from randomized controlled trials (RCTs) in pediatric populations have been inconsistent. For prevention, some trials reported reductions in the incidence of respiratory infections, particularly with daily supplementation or in vitamin D-deficient populations [6], whereas others observed no significant effect [7]. For treatment, RCTs examining vitamin D as an adjunctive therapy in hospitalized children with acute infections have similarly produced divergent results, with some suggesting shorter illness duration and others showing no meaningful clinical benefit [8, 9]. Existing reviews have also underscored the variability in trial outcomes, resulting in ongoing uncertainty about the preventive and therapeutic role of vitamin D in pediatric ARIs.
Given the persistent global burden of these infections and the limited evidence specific to pediatric populations, a systematic review and meta-analysis of RCTs was undertaken to clarify whether vitamin D supplementation prevents the onset of ARIs and improves outcomes among affected children. This updated synthesis aims to address inconsistencies in the literature and provide evidence to guide pediatric clinical practice and public health policy.
Methods
This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [10]. The study protocol was prospectively registered in PROSPERO with registration number: CRD420251133291.
Data sources and search strategy
A comprehensive literature search was conducted in MEDLINE (via PubMed), Embase, Web of Science, the Cochrane Library and SCOPUS from inception to April 2025. The search strategy incorporated both controlled vocabulary (e.g., MeSH and Emtree terms) and free-text keywords. Terms related to vitamin D (including “vitamin D,” “cholecalciferol”), acute respiratory infections (including “acute respiratory infection,” “pneumonia,” “bronchiolitis,” “respiratory tract infection”), and pediatric populations (including “child,” “infant,” “preschool,” “adolescent,” “pediatric”) were used in combination with Boolean operators. No language restrictions were applied. Reference lists of relevant reviews and meta-analyses were hand-searched to identify additional eligible trials.
Eligibility criteria
Study eligibility was established using the PICOS framework. P (Population): Pediatric populations, including neonates, children, and adolescents, regardless of sex, geographic setting, or baseline vitamin D status. I (Intervention): Oral vitamin D supplementation in any form, administered at any dose, frequency, or duration. C (Comparison): Placebo, no treatment, or standard care without vitamin D supplementation. O (Outcome): Trials were required to report at least one relevant outcome, including the incidence of ARIs, duration of hospitalization, time to complete recovery from ARIs, incidence of serious adverse events, or all-cause mortality. S (Study design): Only randomized controlled trials published in peer-reviewed journals were considered.
Studies were excluded if they employed non-randomized or quasi-experimental designs, combined vitamin D with other active interventions without a clearly defined vitamin D-only arm, lacked adequate outcome data, or were available solely as protocols, conference abstracts, or reviews.
Study selection and data extraction
All identified records were imported into EndNote version X9 for deduplication. Two reviewers independently screened the titles and abstracts of all retrieved articles. The full texts of potentially eligible studies were then reviewed in detail to assess compliance with the predefined eligibility criteria. Any disagreements were resolved by discussion, with arbitration from a third reviewer when necessary.
A standardized extraction form was developed to ensure consistency across studies. From each included randomized controlled trial, the following data were collected: study characteristics (first author, publication year, and location), participant demographics (sample size, sex distribution, age range, and mean baseline 25(OH) D level), intervention details (dosage and duration of vitamin D supplementation), comparison group, reported outcomes, and follow-up duration. Data were cross-checked for accuracy, and corresponding authors were contacted in cases of missing or unclear information.
Outcomes
Primary Outcome: Incidence of ARIs: The number of participants who develop one or more ARIs during the study period, as defined by clinical diagnosis (e.g., pneumonia, bronchiolitis, or other ARIs). Secondary Outcomes: Duration of hospitalization: The length of time (in days) that participants are hospitalized due to ARIs; Time to complete recovery from ARIs: The time (in hours) taken for participants to recover from ARIs, defined as the resolution of symptoms as assessed by clinical judgment; Incidence of serious adverse events: The number of participants who experience serious adverse events related to vitamin D supplementation, as reported in the included studies; All-cause mortality: The number of participants who die from any cause during the study period.”
Study quality assessment
The methodological quality of the included studies was evaluated using the Cochrane Risk of Bias tool (version 1.0), as recommended in the Cochrane Handbook for Systematic Reviews of Interventions [11]. Two reviewers independently assessed the risk of bias across seven domains: (1) random sequence generation, (2) allocation concealment, (3) blinding of participants and personnel, (4) blinding of outcome assessment, (5) incomplete outcome data, (6) selective outcome reporting, and (7) other potential sources of bias. Each domain was judged as “low risk,” “high risk,” or “unclear risk” of bias, based on the information provided in the original trial reports. Any discrepancies between the two reviewers were resolved through discussion, and if necessary, a third reviewer was consulted for arbitration. The overall assessments were summarized graphically using RevMan version 5.3.
Data synthesis and analysis
All statistical analyses were conducted using Stata version 16.0 (StataCorp, College Station, TX, USA). For dichotomous outcomes, pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. For continuous outcomes, mean differences (MDs) or standardized mean differences (SMDs) with 95% CIs were used, depending on whether the included trials applied consistent measurement scales. Between-study heterogeneity was quantified using the I² statistic, and I2 values of 25%, 50%, and 75% have been suggested to be indicators of low, moderate, and high heterogeneity, respectively [12]. Pooled estimates were calculated using the random-effect model for all outcome variables due to heterogeneity between the included studies [13]. To explore a potential dose–response relationship, subgroup analyses were prespecified according to the daily equivalent dose of vitamin D supplementation. Guided by prior evidence indicating that preventive benefits, when observed, most consistently occurred with daily regimens in the 400–1000 IU range [14], we applied a two-level categorization of dosing intensity: ≤1000 IU/day versus > 1000 IU/day. Sensitivity analyses were performed for each prespecified outcome by excluding studies that included the neonatal population to evaluate their influence on the overall findings. Publication bias was assessed by visual inspection of funnel plots when at least 10 studies were available for an outcome, supplemented by Egger’s regression test for small-study effects. Statistical significance was defined as a two-sided p value < 0.05.
Results
Study selection and characteristics
The literature search initially identified 2,059 records. After removal of duplicates, 1,331 unique records were screened by title and abstract, leading to the exclusion of 1,221 articles for irrelevance or ineligible study design. Full texts of 110 potentially relevant articles were retrieved and assessed against the eligibility criteria. Of these, 93 were excluded, most commonly because of non-randomized study design (n = 44), unclear diagnosis of acute respiratory infection (n = 27), absence of relevant outcomes (n = 13), or vitamin D administered in combination with other active interventions (n = 9). Seventeen randomized controlled trials were included in the qualitative and quantitative syntheses. The study selection process was summarized in the PRISMA flow diagram (Fig. 1).
Fig. 1.
PRISMA flow diagram of study selection process
The 17 included RCTs comprised a total of 18,372 participants. These studies were conducted across diverse geographic regions including South Asia, the Middle East, Africa, and Europe. The study populations ranged from infants and preschool children hospitalized with severe pneumonia to school-aged children recruited from community or school-based settings. Sample sizes varied widely, from fewer than 50 to over 8,000 participants, and both sexes were represented. The mean or median age differed according to study design, with some trials focusing on infants under one year of age, while others enrolled older children and adolescents. Most interventions evaluated vitamin D₃ supplementation, administered either as daily or weekly regimens, with doses spanning from 200 IU/day equivalents to higher-dose strategies exceeding 100,000 IU intermittently. Control groups consistently received placebo. The duration of supplementation varied widely, from several days in treatment trials of hospitalized children with pneumonia to up to three years in large-scale prevention trials among schoolchildren. Reported outcomes most frequently included incidence of acute respiratory infections, duration of hospitalization, and time to recovery, with several studies also addressing serious adverse events and all-cause mortality. Detailed study characteristics were summarized in Table 1.
Table 1.
General characteristics of included studies
| Study, year | Location | Population (Male: Female) |
Age | Mean baseline 25(OH) D (nmol/L) | Intervention group (IG) | Comparison group (CG) | Outcomes | Follow-up (months) |
|---|---|---|---|---|---|---|---|---|
| Camargo, 2012 [6] | Mongolia |
247 school children (129:118) |
10.1 ± 0.9 years (IG) 9.8 ±1.0 years (CG) |
18.9 ± 9.7 | Vitamin D3 300 IU daily for 7 weeks (n= 143) | Placebo (n = 104) | Incidence of ARIs | 7 weeks |
| Choudhary, 2012 [15] | India |
200 children with severe pneumonia (120:80) |
14.1 ± 12.2 months (IG) 13.8 ± 11.4 months (CG) |
Not determined | Vitamin D3 1,000 IU (age < 1 year) or 2,000 IU (age > 1 year) for 5 days (n = 100) | Placebo (n = 100) |
Duration of hospitalization; Time to complete recovery from ARIs |
5 days |
| Chowdhury, 2021 [16] | Bangladesh |
197 Children with severe pneumonia (124:73) |
8 (5.0, 13.0) months (IG) 10 (5.5, 14.0) months (CG) |
Not determined | Vitamin D3 20,000 IU (age < 6 months), 50,000 IU (age 6–12 months), or 100,000 IU (age 13–59 months) on first day and 10,000 IU for next 4 days (n = 97) | Placebo (n = 100) |
Duration of hospitalization; Time to complete recovery from ARIs; All-cause mortality |
5 days |
| Dubnov-Raz, 2015 [17] | Israel | 54 Adolescent swimmers with vitamin D insufficiency (34:20) |
15.2 ± 1.3 years (IG) 15.1 ± 1.9 years (CG) |
60.4 ± 11.9 | Vitamin D3 2,000 IU daily for 12 weeks (n = 28) | Placebo (n = 27) |
Incidence of ARI; Time to complete recovery from ARIs |
12 weeks |
| Ganmaa, 2020 [18] | Mongolia |
8851 healthy school children (4485:4366) |
9.4 ± 1.6 years (IG) 9.4 ± 1.6 years (CG) |
29.7 ± 10.5 | Vitamin D3 14,000 IU per week for 3 years (n= 4418) | Placebo (n= 4433) |
Incidence of ARIs; Incidence of serious adverse events; All-cause mortality |
3 years |
| Gupta, 2016 [9] | India |
324 Children with pneumonia (226:98) |
16.4 ± 12.9 months (IG) 16.9 ± 13.4 months (CG) |
43.9 ± 33.4 | Vitamin D3 100,000 IU in a single bolus dose (n = 162) | Placebo (n = 162) |
Incidence of ARIs; Duration of hospitalization; Time to complete recovery from ARIs; Incidence of serious adverse events |
6 months |
| Huang, 2022 [19] | Taiwan |
248 Healthy preschool-age children (136:112) |
4.03 ± 0.67 years (IG) 3.76 ± 0.75 years (CG) |
Not determined | Vitamin D 200 IU daily for 1 month (n = 135) | Placebo (n = 113) | Incidence of ARIs | 6 months |
| Kumar, 2011 [20] | India |
2079 Low birthweight infants (970:1109) |
Less than 48 h | Not determined | Vitamin D3 200 IU daily for 6 months (n = 1039) | Placebo (n = 1040) |
Incidence of serious adverse events; All-cause mortality |
6 months |
| Labib, 2021 [21] | Egypt |
191 children with pneumonia (136:55) |
24 (18–48) months (IG) 24 (10–48) months (CG) |
Not determined | Vitamin D3 100,000 IU in a single bolus dose (n = 93) | Placebo (n = 98) |
Duration of hospitalization; All-cause mortality |
1 week |
| Loeb, 2018 [22] | Vietnam |
1,300 Healthy children and adolescents (621:679) |
8.6 ± 3.9 years (IG) 8.4 ± 4.0 years (CG) |
65.5 ± 16.8 | Vitamin D3 14,000 IU per week for 8 months (n= 650) | Placebo (n = 650) | Incidence of ARIs | 8 months |
| Majak, 2011 [23] | Poland |
48 Children with asthma (32:16) |
10.8 ± 3.2 years (IG) 11.1 ± 3.3 years (CG) |
88.9 ± 38.2 | Vitamin D3 500 IU daily for 6 months (n= 24) | Placebo (n = 24) | Incidence of ARIs | 6 months |
| MANASEKI-HOLLAND, 2010 [8] | Afghanistan | 453 Pre-school children with pneumonia (257:196) |
13.18 ± 9.1 months (IG) 13.19 ± 9.2 months (CG) |
Not determined | Vitamin D3 100,000 IU in a single bolus dose (n= 224) | Placebo (n = 229) |
Incidence of ARIs; Time to complete recovery from ARIs |
3 months |
| MANASEKI-HOLLAND, 2012 [7] | Afghanistan | 3,046 Healthy infants (1,591:1,455) | 1–11 months | Not determined | Vitamin D3 100,000 IU quarterly for 18 months (n= 1,524) | Placebo (n = 1,522) | All-cause mortality | 18 months |
| Reyes, 2024 [24] | Chile |
303 Healthy preschool children (168:135) |
25.9 ± 5.5 months (IG1) 27 ± 5.8 months (IG2) 26.2 ± 6 months (CG) |
62.2 ± 15.5 |
Vitamin D3 5,600 IU or 11,200 IU per week for 6 months (n = 204) |
Placebo (n = 99) | Incidence of ARIs | 6 months |
| Somnath, 2017 [25] | India |
154 Children with acute respiratory infection (104:50) |
2 months-5 years | Not determined | Vitamin D3 100,000 IU in a single bolus dose (n = 78) | Placebo (n = 76) |
Duration of hospitalization; All-cause mortality |
3 months |
| URASHIMA, 2010 [26] | Japan | 430 Healthy school children (242:188) |
10.2 ± 2.2 years (IG) 10.4 ± 2.4 years (CG) |
Not determined | Vitamin D3 1,200 IU daily for 4 months (n= 217) | Placebo (n = 213) | Incidence of ARIs | 4 months |
| URASHIMA, 2014 [27] | Japan |
247 High school students (162:85) |
15–18 years | Not determined | Vitamin D3 2000 IU daily for 2 months (n= 148) | Placebo (n = 99) | Incidence of ARIs | 2 months |
ARIs acute respiratory infections, CG Control group, IG Intervention group
Study quality assessment
The methodological quality of the 17 included trials was generally acceptable. Most studies were judged to be at low risk of bias across the key domains of random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, and selective reporting. However, several trials had domains rated as “unclear,” particularly with respect to incomplete outcome data and outcome assessment blinding. For example, three trials had unclear risk of bias for incomplete outcome data, and four trials had unclear risk for selective reporting. One trial also had multiple domains rated as unclear, including allocation concealment and blinding. No trial was judged to be at high risk of bias in any domain. Overall, the body of evidence was considered to be of moderate to high methodological quality, though some uncertainties remain due to incomplete reporting in a minority of studies. Figure 2 summarizes the distribution of risk of bias across all included trials.
Fig. 2.
Risk of bias for included RCTs
Meta-analysis results
Incidence of ARIs
Eleven studies evaluated the effect of vitamin D supplementation on the incidence of ARIs. The pooled analysis showed no statistically significant reduction in ARI incidence (RR = 0.82, 95% CI: 0.64 to 1.06, p = 0.129), with moderate heterogeneity across studies (I² = 61.87%). (Fig. 3) Subgroup analysis based on daily intake showed a significant benefit when the dose was ≤ 1000 IU (RR = 0.42, 95% CI: 0.27 to 0.66, p < 0.001), whereas no protective effect was observed with higher doses (> 1000 IU/day) (RR = 1.02, 95% CI: 0.91 to 1.13, p = 0.788). (Fig. 4)
Fig. 3.
Meta analysis of incidence of ARIs
Fig. 4.
Subgroup analysis of incidence of ARIs based on daily intake
Duration of hospitalization (day)
Five studies reported on the duration of hospitalization. The pooled estimate demonstrated no significant reduction in hospital stay associated with vitamin D supplementation (WMD = 0.03, 95% CI: −0.72 to 0.78, p = 0.940), and there was high heterogeneity among the studies (I² = 88.7%). (Fig. 5)
Fig. 5.
Meta analysis of duration of hospitalization
Time to complete recovery from ARIs (hour)
Five studies assessed the time to complete recovery from ARIs. The meta-analysis found no significant difference between vitamin D and control groups (WMD = −4.36, 95% CI: −11.87 to 3.15, p = 0.255), with moderate heterogeneity (I² = 50.2%). (Fig. 6)
Fig. 6.
Meta analysis of time to complete recovery from ARIs
Incidence of serious adverse events
Three studies reported the incidence of serious adverse events. Pooled results indicated that vitamin D supplementation was associated with a significantly lower risk of serious adverse events (RR = 0.83, 95% CI: 0.71 to 0.96, p = 0.015), and low heterogeneity was observed (I² = 0%). (Fig. 7)
Fig. 7.
Meta analysis of incidence of serious adverse events
All-cause mortality
Six studies reported all-cause mortality. The pooled results showed no significant reduction in mortality with vitamin D supplementation (RR = 0.88, 95% CI: 0.60 to 1.28, p = 0.502), with low heterogeneity (I² = 4.27%). (Fig. 8)
Fig. 8.
Meta analysis of all-cause mortality
To facilitate an intuitive overview of the data, participant allocation and contributions to each outcome were visualized with a Sankey diagram [28]. (Fig. 9)
Fig. 9.
Sankey diagram
Sensitivity analysis
To establish the robustness of prespecified outcomes, sensitivity analyses were performed. Since only the outcomes ‘incidence of serious adverse events’ and ‘all-cause mortality’ included studies that enrolled neonates, sensitivity analyses were conducted for these two outcomes by removing studies that included the neonatal population. The results showed that the overall conclusions did not materially change: incidence of serious adverse events: (RR = 0.81, 95% CI: 0.66 to 0.99, p = 0.040) and all-cause mortality: (RR = 0.73, 95% CI: 0.41 to 1.29, p = 0.279).
Publication bias
Publication bias was assessed only for the incidence of ARIs (11 trials). The funnel plot appeared symmetrical, and Egger’s test indicated no significant small-study effects (p = 0.132), suggesting no evidence of publication bias. (Fig. 10)
Fig. 10.
Funnel plot of the publication bias
Discussion
This systematic review and meta-analysis of 17 randomized controlled trials including 18,372 participants from pediatric populations provides an updated evaluation of the role of vitamin D supplementation in the prevention and treatment of acute respiratory infections. Overall, supplementation did not significantly reduce ARI incidence, hospitalization duration, recovery time, or all-cause mortality. Subgroup analysis, however, revealed that daily doses of ≤ 1000 IU were associated with a significant reduction in ARI incidence, whereas higher doses conferred no benefit. In addition, vitamin D supplementation was linked to a lower risk of serious adverse events, suggesting a favorable safety profile.
Our findings for ARI incidence are broadly consistent with previous meta-analyses that reported null or inconsistent overall effects of vitamin D on respiratory infection outcomes while indicating possible benefit in specific dosing regimens and populations. Martineau et al. and Jolliffe et al., both of which analyzed mixed-age populations, highlighted that protective effects were most evident with daily or weekly supplementation, particularly among individuals with baseline deficiency, whereas intermittent high-dose bolus strategies failed to provide benefit [14, 29]. The present analysis extends this evidence by showing that, in pediatric populations, preventive efficacy was confined to daily low-dose regimens (≤ 1000 IU/day). Several biological mechanisms may explain these findings. Vitamin D enhances innate immunity by inducing antimicrobial peptides such as cathelicidin and β-defensin [30]and modulates adaptive responses by promoting Th2 differentiation and suppressing pro-inflammatory Th1 pathways [31]. These immunomodulatory effects are more likely achieved with sustained physiological supplementation rather than intermittent pharmacological dosing. High-dose bolus regimens may also activate counter-regulatory pathways, including CYP24A1 induction and FGF23 upregulation, which accelerate vitamin D catabolism and may attenuate or abolish its protective effect [32].
By contrast, treatment-related outcomes showed no measurable benefit. Vitamin D supplementation did not shorten hospitalization or accelerate recovery in children with pneumonia, results consistent with earlier pediatric-focused reviews that reported no clear therapeutic effects [33, 34]. These findings suggest that although vitamin D may reduce the risk of developing infection, it is unlikely to substantially modify the clinical course once ARIs are established. Variability in disease severity, baseline vitamin D status, and co-interventions may further explain the lack of effect. Moreover, the absence of therapeutic benefit may reflect the timing of supplementation, as immunomodulatory benefits are more effective in prevention than in altering the trajectory of acute established disease.
Safety outcomes yielded more consistent results. Supplementation was associated with a reduced risk of serious adverse events, and no signal of harm was detected. However, no reduction in all-cause mortality was observed, which is unsurprising given that most trials were not powered to detect rare fatal outcomes. Overall, these findings support vitamin D as a safe intervention in pediatric populations, although expectations regarding mortality benefits should remain conservative.
This study has several notable strengths. It represents the most comprehensive synthesis of randomized controlled trials to date focusing exclusively on pediatric populations across diverse geographic and clinical settings. Rigorous eligibility criteria, a large cumulative sample size, and prespecified subgroup analyses strengthen the reliability of the findings. By incorporating both preventive and therapeutic outcomes, the analysis provides a broad and balanced assessment of the role of vitamin D in pediatric ARIs. Nonetheless, several limitations should be acknowledged. Substantial heterogeneity was observed in some outcomes, particularly hospitalization duration, reducing the precision of pooled estimates. Inconsistent reporting of baseline vitamin D status limited the evaluation of potential effect modification by deficiency. In addition, variability in dosing regimens and intervention durations complicates interpretation and may restrict the generalizability of the findings.
Conclusion
This comprehensive synthesis of pediatric trials indicates that vitamin D supplementation cannot be recommended as a universal intervention for acute respiratory infections in pediatric populations. While daily low-dose regimens may reduce infection risk in populations at risk of deficiency, supplementation does not modify clinical outcomes once infection is established. The consistent safety profile supports targeted use, and future high-quality trials are needed to define optimal dosing strategies and guide clinical and public health practice in high-burden settings.
Abbreviations
- ARIs
Acute respiratory infections
- CG
Control group
- CIs
Confidence intervals
- IG
Intervention group
- MDs
Mean differences
- PRISMA
the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
- RCTs
Randomized controlled trials
- RRs
Risk ratios
- SMDs
Standardized mean differences
Authors’ contributions
LW and KFL contributed to the study conception and design. LW, YBY, and YL performed the literature search and screening. YBY, XY and KFL were responsible for data extraction and validation. XY and YL conducted the statistical analysis and bias assessment. LW and YBY drafted the manuscript. All authors critically reviewed and approved the final version of the manuscript.
Funding
This work was supported by Research Project Program of Hebei Academy of Medical Sciences (No. 20232109).
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.