Childhood growth and development are influenced by a combination of genetic, nutritional, and environmental factors. Among these, chronic infections represent a significant yet underappreciated determinant of growth impairments, particularly in resource-constrained settings. Conditions such as tuberculosis, HIV, and helminthiasis not only increase morbidity and mortality rates but also have long-lasting effects on physical and cognitive development. The global prevalence of stunting, wasting, and underweight in children is alarmingly high, with chronic infections contributing to over 20% of these cases.

The pathophysiology underlying growth impairment in chronic infections is multifaceted. Persistent inflammation induced by infections triggers elevated levels of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which interfere with the growth hormone (GH)–insulin-like growth factor 1 (IGF-1) axis. Nutritional deficits caused by malabsorption, anorexia, and increased metabolic demands further exacerbate these issues. Additionally, chronic infections can disrupt the hypothalamic-pituitary-adrenal (HPA) axis, leading to elevated cortisol levels, which suppress bone growth and muscle development.

Despite significant advancements in medical and nutritional sciences, chronic infections remain a critical challenge to achieving optimal growth outcomes in children. Understanding the complex interactions between infections, immune responses, and growth parameters is essential for devising effective interventions. This study aims to comprehensively evaluate the impact of chronic infections on pediatric growth, focusing on clinical outcomes, biochemical markers, and pathophysiological mechanisms. It also explores potential avenues for intervention and highlights future directions to address this pressing public health issue.

Methodology

This prospective cohort study was conducted over five years, from 2022 to 2024, at tertiary healthcare centers across three regions of India. The study population included 1,200 children aged 0–14 years, selected using a stratified random sampling technique. Eligible participants included children diagnosed with chronic infections such as tuberculosis, HIV, or helminthiasis, confirmed through clinical evaluation, laboratory tests, and imaging studies. Exclusion criteria included acute infections, congenital disorders, or pre-existing endocrine or metabolic conditions that could independently affect growth outcomes.

Baseline data collection involved detailed demographic, socioeconomic, and clinical histories, along with anthropometric measurements, including height, weight, and body mass index (BMI). Growth velocity was assessed using serial height measurements every six months. Laboratory investigations included complete blood counts, inflammatory markers (IL-6, TNF-α), serum albumin levels, and hormonal profiles (growth hormone, insulin-like growth factor 1 [IGF-1], and cortisol). Nutritional status was evaluated through dietary intake surveys and serum micronutrient analysis (iron, zinc, and vitamin D levels). Stool examinations were performed to identify parasitic infections, while chest radiographs, sputum microscopy, and molecular tests (GeneXpert) were used to confirm tuberculosis. HIV status was determined through ELISA and PCR testing.

Participants were categorized into three groups: those with tuberculosis (n=400), HIV (n=400), and helminthiasis (n=400). A control group of 200 age- and sex-matched healthy children was included for comparison. Growth outcomes, including stunting, wasting, and underweight, were assessed using World Health Organization (WHO) growth standards. Statistical analyses were conducted using SPSS (version 25.0). Descriptive statistics were used to summarize baseline characteristics, while the chi-square test, t-test, and analysis of variance (ANOVA) were applied to assess differences between groups. Correlation and regression analyses were used to explore relationships between inflammatory markers, hormonal imbalances, and growth parameters. A p-value of <0.05 was considered statistically significant.

Ethical approval was obtained from the institutional ethics committee, and informed consent was secured from parents or guardians. Children diagnosed with chronic infections received standard treatment as per national guidelines, with additional nutritional supplementation provided where required. Regular follow-ups were conducted to monitor growth and treatment outcomes, ensuring adherence to protocols and minimizing attrition.

This robust methodology allowed for a comprehensive evaluation of the relationship between chronic infections and pediatric growth disorders, providing valuable insights into the pathophysiological mechanisms and potential interventions.

Results

The study population included 1,200 children, of whom 65% were from low-income families. Chronic infections were associated with high rates of stunting (45%), wasting (20%), and underweight (35%). Tuberculosis and helminthiasis were the most commonly identified infections in the cohort.

Prevalence of Growth Disorders

Table 1 shows the prevalence of growth disorders stratified by infection type. Stunting was most common in children with tuberculosis (50%), while wasting was more prevalent in helminthiasis (22%).

The Graph displays the prevalence of growth disorders (Stunting, Wasting, and Underweight) across different infection types (Tuberculosis, Helminthiasis, and HIV). The bars represent the percentage prevalence for each disorder within the respective infection group. ​

Growth Velocity

Children with chronic infections exhibited a 30% reduction in annual growth velocity compared to healthy controls, as shown in Table 2.

The bar graph compares the average annual growth velocity between the Chronic Infections Group and the Healthy Control Group. The graph clearly shows the 30% reduction in growth velocity in the Chronic Infections Group, with error bars representing the standard deviation for each group. ​​

Laboratory Findings

Elevated levels of inflammatory markers (IL-6, TNF-α) and suppressed IGF-1 were observed in all infection groups. Table 3 summarizes the laboratory findings.

The graph displays the laboratory findings across the Tuberculosis, Helminthiasis, and HIV groups, along with the reference range for each parameter. The bars represent the values for each infection group, and the dashed line indicates the reference range for each parameter. ​​

Discussion

This study provides compelling evidence that chronic infections are a major contributor to pediatric growth disorders, with profound implications for long-term health and development. The high prevalence of stunting, wasting, and underweight observed in this cohort aligns with previous studies, underscoring the pervasive impact of infections like tuberculosis, HIV, and helminthiasis on growth outcomes. Stunting, the most common growth disorder in our study, reflects the cumulative effects of chronic inflammation, malnutrition, and endocrine disruption over time.

Elevated levels of IL-6 and TNF-α observed in infected children highlight the central role of inflammation in growth impairment. These cytokines inhibit the action of growth hormone and reduce IGF-1 levels, which are critical for linear growth. The suppression of IGF-1, observed across all infection groups, indicates a systemic disruption of the GH–IGF-1 axis, compounded by the stress-induced elevation of cortisol levels. Chronic infections also impair nutrient absorption, leading to deficiencies in essential vitamins and minerals required for growth, further perpetuating the cycle of malnutrition and infection.

One of the significant findings of this study was the reduced annual growth velocity in children with chronic infections, which was 30% lower than that of healthy controls. This reduction underscores the cumulative impact of systemic inflammation and hormonal imbalances over time. It also suggests that interventions need to be initiated early to minimize the long-term effects of these infections on growth.

The findings also shed light on the socioeconomic dimensions of chronic infections and growth disorders. Children from low-income families were disproportionately affected, reflecting the intersection of poverty, poor sanitation, limited healthcare access, and inadequate nutrition. Addressing these disparities requires a multifaceted approach, including community-based interventions, improved healthcare infrastructure, and public health campaigns to prevent and manage chronic infections.

From a clinical perspective, the study emphasizes the importance of early detection and comprehensive management of growth disorders in children with chronic infections. Biomarkers such as IL-6, TNF-α, and IGF-1 can serve as valuable tools for early identification of at-risk children. Nutritional rehabilitation, anti-inflammatory therapies, and hormonal support should be integrated into care plans to optimize growth outcomes. Public health measures, such as deworming programs, vaccination campaigns, and improvements in sanitation, are essential to reduce the burden of chronic infections in vulnerable populations.

Future research should focus on the reversibility of growth impairments following successful treatment of infections. Longitudinal studies are needed to assess the long-term benefits of integrated interventions and to identify critical windows of opportunity for therapeutic interventions. Advances in molecular biology and immunology offer promising avenues for developing targeted therapies to mitigate the effects of inflammation and endocrine dysregulation on growth.

Future Directions

Future research should focus on developing biomarkers for early detection of growth complications in children with chronic infections. Multidisciplinary care models that integrate nutrition, infection control, and hormonal therapies are essential to optimize outcomes. Public health measures, such as improving sanitation, vaccination programs, and nutritional supplementation, should be prioritized to prevent chronic infections. Longitudinal studies are needed to assess the reversibility of growth impairments following successful treatment of infections.

In conclusion, chronic infections represent a significant barrier to achieving optimal growth and development in children. By addressing the underlying mechanisms of growth impairment and implementing evidence-based interventions, we can improve the health and developmental outcomes of millions of children worldwide.

1. Black RE, Victora CG, Walker SP, et al. Maternal and child undernutrition and overweight in low-income and middle-income countries. 2013;382(9890):427-451. doi:10.1016/S0140-6736(13)60937-X
2. Prendergast AJ, Humphrey JH. The stunting syndrome in developing countries. Paediatr Int Child Health. 2014;34(4):250-265. doi:10.1179/2046905514Y.0000000158
3. World Health Organization (WHO). WHO child growth standards: methods and development. Geneva: WHO Press; 2006.
4. Dewey KG, Begum K. Long-term consequences of stunting in early life. Matern Child Nutr. 2011;7(Suppl 3):5-18. doi:10.1111/j.1740-8709.2011.00349.x
5. Scrimshaw NS, Taylor CE, Gordon JE. Interactions of nutrition and infection. Monogr Ser World Health Organ. 1968;(57):3-329.
6. Taneja S, Bhandari N. Protein-energy malnutrition in India: the plight of our underprivileged children. Indian J Pediatr. 2002;69(7):627-631. doi:10.1007/BF02722675
7. Semba RD, Bloem MW. The anemia of vitamin A deficiency: epidemiology and pathogenesis. Eur J Clin Nutr. 2002;56(4):271-281. doi:10.1038/sj.ejcn.1601310
8. Schürmann N, Jenne CN. Nutrition and infectious diseases: pathophysiological insights from the human immune system. Curr Opin Clin Nutr Metab Care. 2020;23(2):123-129. doi:10.1097/MCO.0000000000000636
9. Van de Perre P. Vertical transmission of HIV-1: routes of infection and prevention strategies. Rev Med Virol. 1999;9(1):1-5. doi:10.1002/(SICI)1099-1654(199901/02)9:1<1::AID-RMV247>3.0.CO;2-3
10. White NJ. Anaemia and malaria. Malar J. 2018;17(1):371. doi:10.1186/s12936-018-2509-9
11. Beisel WR. Nutrition in pediatric infectious diseases. Pediatr Infect Dis J. 1985;4(2):117-122.
12. Keusch GT, Farthing MJG. Nutrition and infection. Annu Rev Nutr. 1986;6:131-154.
13. Gera T, Sachdev HP. Impact of prophylactic supplementation with zinc and iron on growth in children: a systematic review of randomized controlled trials. Public Health Nutr. 1999;2(1):1-13.
14. Rytter MJH, Kolte L, Briend A, et al. The immune system in children with malnutrition—a systematic review. PLoS One. 2014;9(8):e105017. doi:10.1371/journal.pone.0105017
15. DeBoer MD, Lima AA, Oría RB, et al. Early childhood growth failure and malnutrition are associated with metabolic syndrome in later life. J Pediatr Gastroenterol Nutr. 2012;55(5):564-570. doi:10.1097/MPG.0b013e31825ca437
16. Muller O, Krawinkel M. Malnutrition and health in developing countries. 2005;173(3):279-286. doi:10.1503/cmaj.050342
17. de Onis M, Blössner M, Borghi E. Prevalence and trends of stunting among pre-school children, 1990–2020. Public Health Nutr. 2012;15(1):142-148. doi:10.1017/S1368980011001315
18. Golden MH. The development of concepts of malnutrition. J Nutr. 2002;132(7):2117S-2122S.
19. Lozoff B, Beard J, Connor J, et al. Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev. 2006;64(5 Pt 2):S34-S43.
20. GBD 2019 Risk Factors Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis. 2020;396(10258):1204-1222. doi:10.1016/S0140-6736(20)30752-2
21. Thurnham DI. Nutrition of infection and immune function. Br J Nutr. 1997;77(Suppl 1):S1-S112.
22. Kiess W, Popovic V, Armamento-Villareal R, et al. Growth hormone and IGF-1: basic and clinical research in pediatrics. Pediatr Res. 1998;44(6):1-9.
23. Bhutta ZA, Berkley JA, Bandsma RH, et al. Severe childhood malnutrition. Nat Rev Dis Primers. 2017;3:17067. doi:10.1038/nrdp.2017.67
24. Levels and trends in child malnutrition: key findings of the 2021 edition of the joint child malnutrition estimates. New York: UNICEF; 2021.
25. World Health Organization (WHO). The double burden of malnutrition: policy brief. Geneva: WHO Press; 2017.
26. Lawn JE, Cousens S, Zupan J. 4 million neonatal deaths: when? Where? Why? 2005;365(9462):891-900.
27. Walson JL, Berkley JA. The impact of malnutrition on childhood infections. Curr Opin Infect Dis. 2018;31(3):231-236.
28. Grantham-McGregor S, Cheung YB, Cueto S, et al. Developmental potential in the first 5 years for children in developing countries. 2007;369(9555):60-70.
29. Guerrant RL, DeBoer MD, Moore SR, et al. The impoverished gut—a triple burden of diarrhoea, stunting, and chronic disease. Nat Rev Gastroenterol Hepatol. 2013;10(4):220-229.
30. Kumar S, Stecher G, Tamura K. MEGA7: molecular evolutionary genetics analysis version 7.0. Mol Biol Evol. 2016;33(7):1870-1874.
31. Checkley W, Buckley G, Gilman RH, et al. Multi-country analysis of the effects of diarrhoea on childhood stunting. Int J Epidemiol. 2008;37(4):816-830.
32. Haddad L, Cameron L, Barnett I. The double burden of malnutrition in developing countries. 2015;386(10056):2445-2446.
33. Fasina FO, Craig AT. Achieving nutritional adequacy for children in low-income settings. J Glob Health. 2022;12:04050.
34. Victora CG, de Onis M, Hallal PC, et al. Worldwide timing of growth faltering: revisiting implications for interventions. 2010;125(3):e473-e480.