Zinc Deficiency as a Key Determinant of Pneumonia in Early Childhood: A Case-Control Study

Zinc Deficiency as a Key Determinant of Pneumonia in Early Childhood: A Case-Control Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Zinc Deficiency as a Key Determinant of Pneumonia in Early Childhood: A Case-Control Study Linda Jacob, Carol Sara Cherian This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9568816/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Globally, pneumonia is the leading infectious cause of death among young children. Adequate zinc levels are essential for normal immune function, yet zinc deficiency is common in low- and middle-income countries. This case-control study, conducted in a tertiary hospital in central-southern Kerala, examined whether low serum zinc is associated with pneumonia in children aged 6–59 months. The study included 30 children hospitalised with WHO-defined pneumonia (cases) and 30 age-matched children admitted for non-respiratory illnesses (controls). Serum zinc concentrations were measured using atomic absorption spectrometry, with deficiency defined as < 65 µg/dL. Results Zinc deficiency was found in 86.7% of cases (one-third of whom had severe deficiency, < 50 µg/dL) compared with only 26.7% of controls (all mild deficiency; p < 0.001). Mean serum zinc was substantially lower in the pneumonia group (54.0 µg/dL) than in the control group (76.8 µg/dL; p < 0.01). Logistic regression revealed that each 1 µg/dL reduction in serum zinc increased the odds of pneumonia by 15% (OR = 1.15; 95% CI 1.07–1.24). No significant relationships were observed between zinc status and age, sex, weight-for-age, height-for-age, illness severity, or length of hospital stay (all p > 0.05). Conclusions Paediatric pneumonia was strongly associated with low serum zinc in this study population, reinforcing prior evidence that zinc deficiency impairs respiratory immunity. Given the widespread zinc insufficiency among Indian children, improving zinc intake – through supplementation or dietary measures – could help reduce the pneumonia burden. Childhood pneumonia serum zinc micronutrient deficiency case-control study paediatric nutrition immune function Background Pneumonia is the leading infectious cause of death in children under five years of age worldwide ( 1 ). In 2019, it was responsible for approximately 740,000 deaths in this age group, accounting for 14% of child mortality, with the highest burden observed in South Asia and sub-Saharan Africa ( 1 ). The risk of fatal pneumonia is exacerbated by malnutrition, poor living conditions, and low vaccination coverage ( 1 , 2 ). In India, childhood pneumonia remains a significant public health challenge; despite improvements in national control programs, the country still contributes substantially to the global pneumonia mortality burden. Micronutrient status is a critical determinant of immune competence. Zinc, an essential trace element, is vital for maintaining epithelial barrier integrity and supporting various immune pathways ( 3 , 4 ). Zinc deficiency impairs macrophage and T-cell function, reduces the production of antimicrobial peptides, and disrupts cytokine balance( 3 , 4 ). Globally, zinc deficiency affects an estimated 17% of the population, contributing significantly to infection risk; some estimates suggest it may increase pneumonia risk by approximately 20% ( 5 ). Clinical trials and systematic reviews indicate that zinc supplementation can reduce the incidence and duration of respiratory infections in children ( 3 , 4 ). For instance, pooled analyses have shown that zinc supplementation can lower pneumonia incidence by roughly 20% ( 3 ). Despite this context, there are limited Indian studies evaluating serum zinc levels specifically in children with pneumonia. Nutritional surveys reveal suboptimal zinc status among many Indian children; for example, the National Nutrition Survey reported that around 17% of Indian preschoolers had deficient serum zinc levels ( 6 ). This form of "hidden hunger" can occur even in children without overt signs of malnutrition. Given the overlapping burdens of pneumonia and zinc deficiency in India, this study tested the hypothesis that hospitalized children with pneumonia would have lower serum zinc levels than matched controls. The primary aim was to assess the association between zinc status and pneumonia, with a secondary aim to explore whether zinc deficiency correlated with anthropometric measures or disease severity. Methods Study design and participants : A prospective case-control study was conducted at a tertiary care hospital in central southern part of Kerala. Cases were children who met WHO criteria for pneumonia, defined as cough or difficulty breathing accompanied by age-specific tachypnea or chest indrawing ( 2 ). Controls were age-matched children admitted during the same period for non-respiratory acute conditions (e.g., minor injuries, elective surgery) with no history of pneumonia in the preceding month. Exclusion criteria for both groups were: chronic cardiac or pulmonary disease, primary immunodeficiency, severe malnutrition (weight-for-age or height-for-age Z-score < -3), anemia requiring transfusion, recent major surgery, hospital-acquired or aspiration pneumonia, or refusal of consent. Institutional ethical approval was obtained, and written parental consent was secured. Data collection For each participant, data on age, sex, clinical parameters, and anthropometry (weight, height) were recorded. Nutritional status was assessed using WHO Z-scores for weight-for-age and height-for-age. Pneumonia severity was classified according to WHO guidelines. Blood samples were drawn upon admission; serum was separated within 30 minutes, stored at -20°C, and later analyzed for zinc concentration using atomic absorption spectrometry. Zinc deficiency was defined as serum zinc < 65 µg/dL, in accordance with laboratory reference standards and prior studies ( 7 ). Hemoglobin and other routine laboratory investigations were obtained as part of standard clinical care. Statistical analysis Continuous data are presented as mean ± SD or median and categorical data as counts (%). Means were compared using Student's t-test (or Mann-Whitney U test for non-normal distributions), and proportions were compared using chi-square or Fisher's exact test. Logistic regression was employed to estimate odds ratios (OR) for pneumonia per unit change in zinc, adjusting for age and sex. A p-value < 0.05 was considered statistically significant. All analyses were performed using SPSS version 26. Results A total of 30 children with pneumonia (cases) and 30 age- and sex-matched controls were enrolled. The prevalence of malnutrition, as reflected by mean weight-for-age and height-for-age, was comparable between the two groups. Among cases, 20 (67%) had pneumonia with chest indrawing, and 10 (33%) presented with severe pneumonia; however, none required intensive care beyond oxygen support. Serum zinc levels Mean serum zinc (Table 1 ) was significantly lower in cases compared to controls (54.0 ± 11.5 µg/dL vs. 76.8 ± 13.6 µg/dL; p < 0.01). This finding aligns with previous reports indicating that children with lower respiratory tract infections often have depleted zinc levels ( 8 ). Using the predefined cut-off, 26 of 30 cases (86.7%) were zinc-deficient. Among these, 10 (33.3%) had severe deficiency (< 50 µg/dL) and 16 (53.3%) had mild deficiency. In contrast, only 8 of 30 controls (26.7%) exhibited mild zinc deficiency, with no cases of severe deficiency (p < 0.001). Table 1 Comparison of mean serum zinc levels between cases and controls Frequency Mean Zinc levels (mcg/dl) Standard Deviation (SD) Mean difference (CI) t- value p- value CASES 30 54.00 11.57 22.76 (16.23–29.29) 6.97 < 0.01 CONTROLS 30 76.76 13.61 Association with pneumonia risk (Table 2 ): Logistic regression demonstrated a strong association between lower zinc levels and pneumonia status. Each 1 µg/dL decrease in serum zinc was associated with a 15% increase in the odds of pneumonia (OR 1.15; 95% CI 1.07–1.24; p < 0.001). Even after adjusting for covariates, low zinc remained an independent risk factor for pneumonia in this cohort. Table 2 Association of zinc levels and occurrence of pneumonia Variable Crude OR (Odds Ratio) 95% CI (Crude) p-value serum zinc 1.15 (1.07–1.24) < 0.01 No significant relationship was found between serum zinc and anthropometric indices; mean weight-for-age and height-for-age did not differ between zinc-deficient and zinc-replete children (in either cases or controls). Similarly, zinc status was not significantly correlated with measures of disease severity, length of hospital stay, or presence of anemia (all p > 0.05). This suggests that zinc deficiency often remained "hidden" in children who did not show overt signs of malnutrition. Discussion This case-control study found that hospitalized children with pneumonia had significantly lower serum zinc levels compared to matched controls without respiratory illness. The prevalence of zinc deficiency was substantially higher among pneumonia cases. These results are consistent with observational evidence that inadequate zinc impairs immune defenses against respiratory pathogens( 8 ). and with previous studies reporting reduced zinc levels in pediatric pneumonia cases. For instance, Natroshvili et al. (2025) reported lower zinc levels in children with severe community-acquired pneumonia compared to those with milder cases,( 3 ). and La et al. (2024) found that Vietnamese children with pneumonia and low zinc required more respiratory support and longer treatment( 9 ). Our study extends this literature by quantifying the zinc-pneumonia association in an Indian setting. The adjusted odds ratio (OR 1.15 per µg/dL decrease in zinc) indicates a notable dose-response relationship, where even modest declines in zinc levels appear to elevate pneumonia risk. We observed that zinc deficiency frequently occurred independently of stunting or general malnutrition, supporting the concept of "hidden hunger" for micronutrients ( 6 ). Nationally, approximately 17% of Indian preschool children have low zinc levels; ( 6 ) however, the prevalence in our pneumonia cases was fivefold higher. This suggests that pneumonic illness may both result from and contribute to zinc depletion: infection increases zinc utilization and losses, while pre-existing deficiency compromises resistance. From a mechanistic perspective, zinc is known to enhance barrier function and pathogen clearance in the lungs ( 4 ). It helps maintain airway epithelial integrity and supports innate immune responses, including those of macrophages and neutrophils, which target respiratory microbes. Deficiency weakens these defenses, potentially leading to unchecked infection and inflammation. Indeed, zinc supplementation trials have demonstrated a reduced incidence of pneumonia and faster recovery times ( 3 , 4 ). Our findings underscore the potential value of zinc in pneumonia control strategies. Ensuring adequate zinc intake through diet, breastfeeding, and supplementation is recommended by WHO as part of integrated pneumonia prevention( 1 , 4 ). The data presented here reinforce that recommendation. Notably, we did not find a correlation between zinc levels and pneumonia severity or nutritional status. While some studies report an association between zinc deficiency and more severe pneumonia,( 3 ) others, like ours, find a weaker link. The modest sample size and limited range of severity in our cohort may have reduced the power to detect such associations. Nevertheless, the absence of obvious clinical predictors for zinc deficiency (such as differences in weight-for-age / height-for-age) highlights the importance of biochemical screening. Children can be zinc-deficient despite appearing nutritionally normal; this "micronutrient invisibility" suggests that routine nutritional assessments should consider micronutrient status beyond just weight or height. Limitations This study has several limitations. The case-control design can demonstrate association but cannot establish causation. Although we excluded several known confounders, unmeasured factors (such as detailed dietary history or other concurrent micronutrient deficiencies) could have influenced the results. The sample size was relatively small and derived from a single center, which may limit the generalizability of the findings. Additionally, zinc levels were measured only at a single time point; acute infection itself can alter zinc distribution as part of the acute-phase response. We attempted to mitigate this by collecting samples early in the hospital stay. Future larger studies, preferably with prospective cohort designs, are needed to confirm these findings and to better clarify the causal direction. Conclusions The findings provide strong evidence that zinc deficiency is an independent risk factor for pneumonia in young children. Children hospitalized with pneumonia had markedly lower serum zinc levels than controls, even when their nutritional status appeared otherwise normal. These results suggest that improving zinc nutrition could be an effective component of pediatric pneumonia prevention strategies, particularly in high-burden countries. We recommend that clinicians consider assessing zinc status in at-risk children, and that public health policies continue to emphasize zinc-rich diets, breastfeeding, and supplementation as integral parts of child health programs. Abbreviations Abbreviation Full form WHO World Health Organization SPSS Statistical Package for the Social Sciences OR Odds ratio CI Confidence interval SD Standard deviation p Probability value (statistical significance) Declarations Ethics approval and consent to participate The study was approved by the Institutional Review Board of [name removed for blinding] and written informed consent was obtained from parents/guardians. Consent for publication Not applicable (no individual person’s data are presented). Availability of data and materials The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding No external funding was received for this study. Acknowledgements We thank the patients and families for their participation, and the laboratory staff for assistance with zinc analyses. Author Contribution LJ and CSC contributed substantially to the conception and design of the study. LJ performed data acquisition, including patient enrolment, clinical data collection, and sample handling. LJ also supervised the laboratory analyses (serum zinc measurement by atomic absorption spectrometry) and conducted the statistical analysis using SPSS. Both authors contributed to the interpretation of data. LJ drafted the initial manuscript, and CSC critically revised it for important intellectual content. Both authors reviewed and approved the final version of the manuscript. All authors agree to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. References World Health Organization (2026) Pneumonia in children. https://www.who.int/news-room/fact-sheets/detail/pneumonia . Accessed 22 Apr 2026 World Health Organization (2014) Revised WHO classification and treatment of pneumonia in children at health facilities: evidence summaries. World Health Organization, Geneva Natroshvili M, Chkhaidze M (2025) Impact of Zinc Deficiency on the Severity of Pneumonia in Pediatric Patients: A Cross-Sectional Study. Cureus 17(12):e98383. 10.7759/cureus.98383 Dinardo G, Indolfi C, Klain A, Grella C, Tosca MA, Miraglia del Giudice M et al (2026) The Role of Zinc in Pediatric Respiratory Infections: Evidence from Clinical Trials and Real-World Studies. Nutrients 18(4):557. 10.3390/nu18040557 World Health Organization (2025) Zinc Supplementation in Children With Respiratory Infections. https://www.who.int/tools/elena/commentary/zinc-respiratory-infection . Accessed 22 Apr 2026 Pullakhandam R, Agrawal PK, Peter R, Ghosh S, Reddy GB, Kulkarni B et al (2021) Prevalence of low serum zinc concentrations in Indian children and adolescents: findings from the Comprehensive National Nutrition Survey 2016-18. Am J Clin Nutr 114(2):638–648. 10.1093/ajcn/nqab066 Hotz C, Peerson JM, Brown KH (2003) Suggested lower cutoffs of serum zinc concentrations for assessing zinc status: reanalysis of the second National Health and Nutrition Examination Survey data (1976–1980). Am J Clin Nutr 78(4):756–764. 10.1093/ajcn/78.4.756 Sazawal S, Black RE, Jalla S, Mazumdar S, Sinha A, Bhan MK (1998) Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial. Pediatrics 102(1 Pt 1):1–5. 10.1542/peds.102.1.1 La Q, Lư D, Le S (2024) Relationship between serum zinc levels and the burden of treatment in children with pneumonia. Int J Contemp Pediatr 11:1177–1182. 10.18203/2349-3291.ijcp20242328 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 10 May, 2026 Reviewers agreed at journal 10 May, 2026 Reviewers agreed at journal 06 May, 2026 Reviewers invited by journal 03 May, 2026 Editor assigned by journal 03 May, 2026 Submission checks completed at journal 03 May, 2026 First submitted to journal 29 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9568816","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":635671664,"identity":"a2e9eadb-ded7-4bd3-a15f-dc99532b5655","order_by":0,"name":"Linda Jacob","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYBACPmYGBgkGHiBLgrHx4YcKIIOZuQGvFjaEFuZmY4kzIC2MBLSAFINZEuxtErxtIBYhLey8B2/8kLGT55dubJCQnFcbzd8O1PKjYhseh/ElW/bwJBvOnHOwwaBw2/HcGYcZGxh7ztzGo4XHTIKHhznB4EZiQ4LktmO5DUAtzIxt+LVI/uGpB2s5wDvnWO58YrRI8/AcBmlpbOBtqMndQIQWY2sZnuMgvzQzSxw7kLsRqOUgPr/w858xvPm2pxoYYu3Pf36oqcudd/7wwQc/KnBrAQPGHjjzMJg8gF89CPyAs+oIKx4Fo2AUjIIRBwAI9lT/TeYCeQAAAABJRU5ErkJggg==","orcid":"","institution":"Pushpagiri Institute of Medical Sciences \u0026 Research Centre","correspondingAuthor":true,"prefix":"","firstName":"Linda","middleName":"","lastName":"Jacob","suffix":""},{"id":635671665,"identity":"a2981a55-b15e-4e1f-bef5-a8e9d65d9df2","order_by":1,"name":"Carol Sara Cherian","email":"","orcid":"","institution":"Pushpagiri Institute of Medical Sciences \u0026 Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Carol","middleName":"Sara","lastName":"Cherian","suffix":""}],"badges":[],"createdAt":"2026-04-29 17:39:49","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9568816/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9568816/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109067816,"identity":"9793beda-c769-49ac-80cd-94259abc6475","added_by":"auto","created_at":"2026-05-12 10:01:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":161806,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9568816/v1/71debb8b-dfe8-455b-b8b6-acb5c8e086a4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eZinc Deficiency as a Key Determinant of Pneumonia in Early Childhood: A Case-Control Study\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003ePneumonia is the leading infectious cause of death in children under five years of age worldwide (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). In 2019, it was responsible for approximately 740,000 deaths in this age group, accounting for 14% of child mortality, with the highest burden observed in South Asia and sub-Saharan Africa (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The risk of fatal pneumonia is exacerbated by malnutrition, poor living conditions, and low vaccination coverage (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). In India, childhood pneumonia remains a significant public health challenge; despite improvements in national control programs, the country still contributes substantially to the global pneumonia mortality burden.\u003c/p\u003e \u003cp\u003eMicronutrient status is a critical determinant of immune competence. Zinc, an essential trace element, is vital for maintaining epithelial barrier integrity and supporting various immune pathways (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Zinc deficiency impairs macrophage and T-cell function, reduces the production of antimicrobial peptides, and disrupts cytokine balance(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Globally, zinc deficiency affects an estimated 17% of the population, contributing significantly to infection risk; some estimates suggest it may increase pneumonia risk by approximately 20% (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Clinical trials and systematic reviews indicate that zinc supplementation can reduce the incidence and duration of respiratory infections in children (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). For instance, pooled analyses have shown that zinc supplementation can lower pneumonia incidence by roughly 20% (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite this context, there are limited Indian studies evaluating serum zinc levels specifically in children with pneumonia. Nutritional surveys reveal suboptimal zinc status among many Indian children; for example, the National Nutrition Survey reported that around 17% of Indian preschoolers had deficient serum zinc levels (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). This form of \"hidden hunger\" can occur even in children without overt signs of malnutrition. Given the overlapping burdens of pneumonia and zinc deficiency in India, this study tested the hypothesis that hospitalized children with pneumonia would have lower serum zinc levels than matched controls. The primary aim was to assess the association between zinc status and pneumonia, with a secondary aim to explore whether zinc deficiency correlated with anthropometric measures or disease severity.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cb\u003eStudy design and participants\u003c/b\u003e: A prospective case-control study was conducted at a tertiary care hospital in central southern part of Kerala. Cases were children who met WHO criteria for pneumonia, defined as cough or difficulty breathing accompanied by age-specific tachypnea or chest indrawing (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Controls were age-matched children admitted during the same period for non-respiratory acute conditions (e.g., minor injuries, elective surgery) with no history of pneumonia in the preceding month. Exclusion criteria for both groups were: chronic cardiac or pulmonary disease, primary immunodeficiency, severe malnutrition (weight-for-age or height-for-age Z-score \u0026lt; -3), anemia requiring transfusion, recent major surgery, hospital-acquired or aspiration pneumonia, or refusal of consent. Institutional ethical approval was obtained, and written parental consent was secured.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eData collection\u003c/strong\u003e \u003cp\u003eFor each participant, data on age, sex, clinical parameters, and anthropometry (weight, height) were recorded. Nutritional status was assessed using WHO Z-scores for weight-for-age and height-for-age. Pneumonia severity was classified according to WHO guidelines. Blood samples were drawn upon admission; serum was separated within 30 minutes, stored at -20\u0026deg;C, and later analyzed for zinc concentration using atomic absorption spectrometry. Zinc deficiency was defined as serum zinc\u0026thinsp;\u0026lt;\u0026thinsp;65 \u0026micro;g/dL, in accordance with laboratory reference standards and prior studies (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Hemoglobin and other routine laboratory investigations were obtained as part of standard clinical care.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eStatistical analysis\u003c/strong\u003e \u003cp\u003eContinuous data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or median and categorical data as counts (%). Means were compared using Student's t-test (or Mann-Whitney U test for non-normal distributions), and proportions were compared using chi-square or Fisher's exact test. Logistic regression was employed to estimate odds ratios (OR) for pneumonia per unit change in zinc, adjusting for age and sex. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. All analyses were performed using SPSS version 26.\u003c/p\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 30 children with pneumonia (cases) and 30 age- and sex-matched controls were enrolled. The prevalence of malnutrition, as reflected by mean weight-for-age and height-for-age, was comparable between the two groups. Among cases, 20 (67%) had pneumonia with chest indrawing, and 10 (33%) presented with severe pneumonia; however, none required intensive care beyond oxygen support.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eSerum zinc levels\u003c/strong\u003e \u003cp\u003eMean serum zinc (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) was significantly lower in cases compared to controls (54.0\u0026thinsp;\u0026plusmn;\u0026thinsp;11.5 \u0026micro;g/dL vs. 76.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6 \u0026micro;g/dL; p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). This finding aligns with previous reports indicating that children with lower respiratory tract infections often have depleted zinc levels (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Using the predefined cut-off, 26 of 30 cases (86.7%) were zinc-deficient. Among these, 10 (33.3%) had severe deficiency (\u0026lt;\u0026thinsp;50 \u0026micro;g/dL) and 16 (53.3%) had mild deficiency. In contrast, only 8 of 30 controls (26.7%) exhibited mild zinc deficiency, with no cases of severe deficiency (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\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\u003eComparison of mean serum zinc levels between cases and controls\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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 \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean Zinc levels\u003c/p\u003e \u003cp\u003e(mcg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStandard Deviation (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean difference (CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003et-\u003c/p\u003e \u003cp\u003evalue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep-\u003c/p\u003e \u003cp\u003evalue\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCASES\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e54.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e22.76\u003c/p\u003e \u003cp\u003e(16.23\u0026ndash;29.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e6.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCONTROLS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e76.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13.61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eAssociation with pneumonia risk\u003c/b\u003e (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e): Logistic regression demonstrated a strong association between lower zinc levels and pneumonia status. Each 1 \u0026micro;g/dL decrease in serum zinc was associated with a 15% increase in the odds of pneumonia (OR 1.15; 95% CI 1.07\u0026ndash;1.24; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Even after adjusting for covariates, low zinc remained an independent risk factor for pneumonia in this cohort.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation of zinc levels and occurrence of pneumonia\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCrude OR (Odds Ratio)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI (Crude)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eserum zinc\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(1.07\u0026ndash;1.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNo significant relationship was found between serum zinc and anthropometric indices; mean weight-for-age and height-for-age did not differ between zinc-deficient and zinc-replete children (in either cases or controls). Similarly, zinc status was not significantly correlated with measures of disease severity, length of hospital stay, or presence of anemia (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). This suggests that zinc deficiency often remained \"hidden\" in children who did not show overt signs of malnutrition.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case-control study found that hospitalized children with pneumonia had significantly lower serum zinc levels compared to matched controls without respiratory illness. The prevalence of zinc deficiency was substantially higher among pneumonia cases. These results are consistent with observational evidence that inadequate zinc impairs immune defenses against respiratory pathogens(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). and with previous studies reporting reduced zinc levels in pediatric pneumonia cases. For instance, Natroshvili et al. (2025) reported lower zinc levels in children with severe community-acquired pneumonia compared to those with milder cases,(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). and La et al. (2024) found that Vietnamese children with pneumonia and low zinc required more respiratory support and longer treatment(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur study extends this literature by quantifying the zinc-pneumonia association in an Indian setting. The adjusted odds ratio (OR 1.15 per \u0026micro;g/dL decrease in zinc) indicates a notable dose-response relationship, where even modest declines in zinc levels appear to elevate pneumonia risk. We observed that zinc deficiency frequently occurred independently of stunting or general malnutrition, supporting the concept of \"hidden hunger\" for micronutrients (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Nationally, approximately 17% of Indian preschool children have low zinc levels; (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) however, the prevalence in our pneumonia cases was fivefold higher. This suggests that pneumonic illness may both result from and contribute to zinc depletion: infection increases zinc utilization and losses, while pre-existing deficiency compromises resistance.\u003c/p\u003e \u003cp\u003eFrom a mechanistic perspective, zinc is known to enhance barrier function and pathogen clearance in the lungs (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). It helps maintain airway epithelial integrity and supports innate immune responses, including those of macrophages and neutrophils, which target respiratory microbes. Deficiency weakens these defenses, potentially leading to unchecked infection and inflammation. Indeed, zinc supplementation trials have demonstrated a reduced incidence of pneumonia and faster recovery times (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Our findings underscore the potential value of zinc in pneumonia control strategies. Ensuring adequate zinc intake through diet, breastfeeding, and supplementation is recommended by WHO as part of integrated pneumonia prevention(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The data presented here reinforce that recommendation.\u003c/p\u003e \u003cp\u003eNotably, we did not find a correlation between zinc levels and pneumonia severity or nutritional status. While some studies report an association between zinc deficiency and more severe pneumonia,(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) others, like ours, find a weaker link. The modest sample size and limited range of severity in our cohort may have reduced the power to detect such associations. Nevertheless, the absence of obvious clinical predictors for zinc deficiency (such as differences in weight-for-age / height-for-age) highlights the importance of biochemical screening. Children can be zinc-deficient despite appearing nutritionally normal; this \"micronutrient invisibility\" suggests that routine nutritional assessments should consider micronutrient status beyond just weight or height.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eLimitations\u003c/strong\u003e \u003cp\u003eThis study has several limitations. The case-control design can demonstrate association but cannot establish causation. Although we excluded several known confounders, unmeasured factors (such as detailed dietary history or other concurrent micronutrient deficiencies) could have influenced the results. The sample size was relatively small and derived from a single center, which may limit the generalizability of the findings. Additionally, zinc levels were measured only at a single time point; acute infection itself can alter zinc distribution as part of the acute-phase response. We attempted to mitigate this by collecting samples early in the hospital stay. Future larger studies, preferably with prospective cohort designs, are needed to confirm these findings and to better clarify the causal direction.\u003c/p\u003e \u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe findings provide strong evidence that zinc deficiency is an independent risk factor for pneumonia in young children. Children hospitalized with pneumonia had markedly lower serum zinc levels than controls, even when their nutritional status appeared otherwise normal. These results suggest that improving zinc nutrition could be an effective component of pediatric pneumonia prevention strategies, particularly in high-burden countries. We recommend that clinicians consider assessing zinc status in at-risk children, and that public health policies continue to emphasize zinc-rich diets, breastfeeding, and supplementation as integral parts of child health programs.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"545\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAbbreviation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFull form\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eWHO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eWorld Health Organization\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSPSS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eStatistical Package for the Social Sciences\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eOdds ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eConfidence interval\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eStandard deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eProbability value (statistical significance)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Institutional Review Board of [name removed for blinding] and written informed consent was obtained from parents/guardians.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable (no individual person\u0026rsquo;s data are presented).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo external funding was received for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the patients and families for their participation, and the laboratory staff for assistance with zinc analyses.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eLJ and CSC contributed substantially to the conception and design of the study. LJ performed data acquisition, including patient enrolment, clinical data collection, and sample handling. LJ also supervised the laboratory analyses (serum zinc measurement by atomic absorption spectrometry) and conducted the statistical analysis using SPSS. Both authors contributed to the interpretation of data. LJ drafted the initial manuscript, and CSC critically revised it for important intellectual content. Both authors reviewed and approved the final version of the manuscript. All authors agree to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWorld Health Organization (2026) Pneumonia in children. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.who.int/news-room/fact-sheets/detail/pneumonia\u003c/span\u003e\u003cspan address=\"https://www.who.int/news-room/fact-sheets/detail/pneumonia\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Accessed 22 Apr 2026\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization (2014) Revised WHO classification and treatment of pneumonia in children at health facilities: evidence summaries. World Health Organization, Geneva\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNatroshvili M, Chkhaidze M (2025) Impact of Zinc Deficiency on the Severity of Pneumonia in Pediatric Patients: A Cross-Sectional Study. Cureus 17(12):e98383. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7759/cureus.98383\u003c/span\u003e\u003cspan address=\"10.7759/cureus.98383\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDinardo G, Indolfi C, Klain A, Grella C, Tosca MA, Miraglia del Giudice M et al (2026) The Role of Zinc in Pediatric Respiratory Infections: Evidence from Clinical Trials and Real-World Studies. 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Accessed 22 Apr 2026\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePullakhandam R, Agrawal PK, Peter R, Ghosh S, Reddy GB, Kulkarni B et al (2021) Prevalence of low serum zinc concentrations in Indian children and adolescents: findings from the Comprehensive National Nutrition Survey 2016-18. Am J Clin Nutr 114(2):638\u0026ndash;648. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/ajcn/nqab066\u003c/span\u003e\u003cspan address=\"10.1093/ajcn/nqab066\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHotz C, Peerson JM, Brown KH (2003) Suggested lower cutoffs of serum zinc concentrations for assessing zinc status: reanalysis of the second National Health and Nutrition Examination Survey data (1976\u0026ndash;1980). Am J Clin Nutr 78(4):756\u0026ndash;764. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/ajcn/78.4.756\u003c/span\u003e\u003cspan address=\"10.1093/ajcn/78.4.756\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSazawal S, Black RE, Jalla S, Mazumdar S, Sinha A, Bhan MK (1998) Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial. Pediatrics 102(1 Pt 1):1\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1542/peds.102.1.1\u003c/span\u003e\u003cspan address=\"10.1542/peds.102.1.1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLa Q, Lư D, Le S (2024) Relationship between serum zinc levels and the burden of treatment in children with pneumonia. Int J Contemp Pediatr 11:1177\u0026ndash;1182. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.18203/2349-3291.ijcp20242328\u003c/span\u003e\u003cspan address=\"10.18203/2349-3291.ijcp20242328\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"egyptian-pediatric-association-gazette","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"epag","sideBox":"Learn more about [Egyptian Pediatric Association Gazette](https://epag.springeropen.com)","snPcode":"43054","submissionUrl":"https://submission.springernature.com/new-submission/43054/3?","title":"Egyptian Pediatric Association Gazette","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Childhood pneumonia, serum zinc, micronutrient deficiency, case-control study, paediatric nutrition, immune function","lastPublishedDoi":"10.21203/rs.3.rs-9568816/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9568816/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eGlobally, pneumonia is the leading infectious cause of death among young children. Adequate zinc levels are essential for normal immune function, yet zinc deficiency is common in low- and middle-income countries. This case-control study, conducted in a tertiary hospital in central-southern Kerala, examined whether low serum zinc is associated with pneumonia in children aged 6\u0026ndash;59 months. The study included 30 children hospitalised with WHO-defined pneumonia (cases) and 30 age-matched children admitted for non-respiratory illnesses (controls). Serum zinc concentrations were measured using atomic absorption spectrometry, with deficiency defined as \u0026lt;\u0026thinsp;65 \u0026micro;g/dL.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eZinc deficiency was found in 86.7% of cases (one-third of whom had severe deficiency, \u0026lt;\u0026thinsp;50 \u0026micro;g/dL) compared with only 26.7% of controls (all mild deficiency; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Mean serum zinc was substantially lower in the pneumonia group (54.0 \u0026micro;g/dL) than in the control group (76.8 \u0026micro;g/dL; p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Logistic regression revealed that each 1 \u0026micro;g/dL reduction in serum zinc increased the odds of pneumonia by 15% (OR\u0026thinsp;=\u0026thinsp;1.15; 95% CI 1.07\u0026ndash;1.24). No significant relationships were observed between zinc status and age, sex, weight-for-age, height-for-age, illness severity, or length of hospital stay (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003ePaediatric pneumonia was strongly associated with low serum zinc in this study population, reinforcing prior evidence that zinc deficiency impairs respiratory immunity. Given the widespread zinc insufficiency among Indian children, improving zinc intake \u0026ndash; through supplementation or dietary measures \u0026ndash; could help reduce the pneumonia burden.\u003c/p\u003e","manuscriptTitle":"Zinc Deficiency as a Key Determinant of Pneumonia in Early Childhood: A Case-Control Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-11 17:32:24","doi":"10.21203/rs.3.rs-9568816/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-10T17:57:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"231247747126412742467153218519006829512","date":"2026-05-10T14:06:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"329056794964439559855714747418438842684","date":"2026-05-06T04:12:46+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-05-04T03:38:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-05-04T01:55:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-05-04T01:54:57+00:00","index":"","fulltext":""},{"type":"submitted","content":"Egyptian Pediatric Association Gazette","date":"2026-04-29T17:28:07+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"egyptian-pediatric-association-gazette","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"epag","sideBox":"Learn more about [Egyptian Pediatric Association Gazette](https://epag.springeropen.com)","snPcode":"43054","submissionUrl":"https://submission.springernature.com/new-submission/43054/3?","title":"Egyptian Pediatric Association Gazette","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"fdd529c4-37f9-499d-96d5-199b2bb33e9a","owner":[],"postedDate":"May 11th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-10T17:57:05+00:00","index":61,"fulltext":""},{"type":"reviewerAgreed","content":"231247747126412742467153218519006829512","date":"2026-05-10T14:06:45+00:00","index":60,"fulltext":""},{"type":"reviewerAgreed","content":"329056794964439559855714747418438842684","date":"2026-05-06T04:12:46+00:00","index":56,"fulltext":""},{"type":"reviewersInvited","content":"35","date":"2026-05-04T03:38:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-05-04T01:55:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-05-04T01:54:57+00:00","index":"","fulltext":""},{"type":"submitted","content":"Egyptian Pediatric Association Gazette","date":"2026-04-29T17:28:07+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-11T17:32:24+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-11 17:32:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9568816","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9568816","identity":"rs-9568816","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}