Volume 95, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Inflammation has been associated with cardiovascular disease and other health outcomes in children and adults, yet few longitudinal data are available on prevalence and predictors of inflammation in infants. We aimed to identify the prevalence of inflammation in a cohort of Bolivian infants and estimate its association with acute (recent illnesses) and chronic (overweight, stunting) morbidities and potential pathogen exposure (represented by water, sanitation, and hygiene [WASH] resources). We measured plasma concentrations of two acute phase proteins (C-reactive protein [CRP], marking acute inflammation, and alpha(1)-acid-glycoprotein [AGP], marking chronic inflammation) at three time points (target 2, 6–8, and 12–18 months). Of 451 singleton infants enrolled in the parent study, 272 had the first blood draw and complete data. Anthropometry and sociodemographic and recent illness data (2-week recall of cough, diarrhea, and fever) were collected at each visit. Inflammation was defined as CRP > 5 mg/L or AGP > 1 g/L. The prevalence of inflammation increased from early infancy (3% at first blood draw) to later infancy (15–22% at later blood draws). Recent cough, recent fever, and age in months were significantly associated with relative increases in CRP (7–44%) and AGP (5–23%), whereas recent diarrhea was only significantly associated with an increase in CRP (48%). Neither anthropometry nor WASH was significantly associated with inflammation. Results confirm the role of recent acute illness in inflammation in infants, and indicate that adiposity and WASH are not as important to inflammation in this age category.


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  1. Pepys MB, Hirschfield GM, , 2003. C-reactive protein: a critical update. J Clin Invest 111: 18051812.[Crossref] [Google Scholar]
  2. Pai JK, Pischon T, Ma J, Manson JE, Hankinson SE, Joshipura K, Curhan GC, Rifai N, Cannuscio CC, Stampfer MJ, Rimm EB, , 2004. Inflammatory markers and the risk of coronary heart disease in men and women. N Engl J Med 351: 25992610.[Crossref] [Google Scholar]
  3. Koenig W, , 2013. High-sensitivity C-reactive protein and atherosclerotic disease: from improved risk prediction to risk-guided therapy. Int J Cardiol 168: 51265134.[Crossref] [Google Scholar]
  4. Reus GZ, Fries GR, Stertz L, Badawy M, Passos IC, Barichello T, Kapczinski F, Quevedo J, , 2015. The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders. Neuroscience 300: 141154.[Crossref] [Google Scholar]
  5. Furtado M, Katzman MA, , 2015. Examining the role of neuroinflammation in major depression. Psychiatry Res 229: 2736.[Crossref] [Google Scholar]
  6. Kosek M, Haque R, Lima A, Babji S, Shrestha S, Qureshi S, Amidou S, Mduma E, Lee G, Yori PP, Guerrant RL, Bhutta Z, Mason C, Kang G, Kabir M, Amour C, Bessong P, Turab A, Seidman J, Olortegui MP, Quetz J, Lang D, Gratz J, Miller M, Gottlieb M, MAL-ED Network; , 2013. Fecal markers of intestinal inflammation and permeability associated with the subsequent acquisition of linear growth deficits in infants. Am J Trop Med Hyg 88: 390396.[Crossref] [Google Scholar]
  7. Garcia-Anguita A, Kakourou A, Tsilidis KK, , 2015. Biomarkers of inflammation and immune function and risk of colorectal cancer. Curr Colorectal Cancer Rep 11: 250258.[Crossref] [Google Scholar]
  8. Rivas-Fuentes S, Salgado-Aguayo A, Pertuz Belloso S, Gorocica Rosete P, Alvarado-Vasquez N, Aquino-Jarquin G, , 2015. Role of chemokines in non-small cell lung cancer: angiogenesis and inflammation. J Cancer 6: 938952.[Crossref] [Google Scholar]
  9. Thurnham D, McCabe G, World Health Organization, 2012. Influence of infection and inflammation on biomarkers of nutritional status with an emphasis on vitamin A and iron. , ed. Report: Priorities in the Assessment of Vitamin A and Iron Status in Populations, Panama City, Panama, 15–17 September 2010. Geneva, Switzerland: World Health Organization. [Google Scholar]
  10. Rytter MJ, Kolte L, Briend A, Friis H, Christensen VB, , 2014. The immune system in children with malnutrition: a systematic review. PLoS One 9: e105017.[Crossref] [Google Scholar]
  11. Fagundes CP, Glaser R, Kiecolt-Glaser JK, , 2013. Stressful early life experiences and immune dysregulation across the lifespan. Brain Behav Immun 27: 812.[Crossref] [Google Scholar]
  12. Raiten DJ, Sakr Ashour FA, Ross AC, Meydani SN, Dawson HD, Stephensen CB, Brabin BJ, Suchdev PS, van Ommen B, INSPIRE Consultative Group; , 2015. Inflammation and nutritional science for programs/policies and interpretation of research evidence (INSPIRE). J Nutr 145: 1039S1108S.[Crossref] [Google Scholar]
  13. Berg AH, Scherer PE, , 2005. Adipose tissue, inflammation, and cardiovascular disease. Circ Res 96: 939949.[Crossref] [Google Scholar]
  14. Choi J, Joseph L, Pilote L, , 2013. Obesity and C-reactive protein in various populations: a systematic review and meta-analysis. Obes Rev 14: 232244.[Crossref] [Google Scholar]
  15. Warnberg J, Marcos A, , 2008. Low-grade inflammation and the metabolic syndrome in children and adolescents. Curr Opin Lipidol 19: 1115.[Crossref] [Google Scholar]
  16. Hadley C, Decaro JA, , 2014. Testing hypothesized predictors of immune activation in Tanzanian infants and children: community, household, caretaker, and child effects. Am J Hum Biol 26: 523529.[Crossref] [Google Scholar]
  17. Dowd JB, Zajacova A, Aiello AE, , 2010. Predictors of inflammation in U.S. children aged 3–16 years. Am J Prev Med 39: 314320.[Crossref] [Google Scholar]
  18. McDade TW, Leonard WR, Burhop J, Reyes-Garcia V, Vadez V, Huanca T, Godoy RA, , 2005. Predictors of C-reactive protein in Tsimane' 2 to 15 year-olds in lowland Bolivia. Am J Phys Anthropol 128: 906913.[Crossref] [Google Scholar]
  19. McDade TW, Rutherford JN, Adair L, Kuzawa C, , 2009. Population differences in associations between C-reactive protein concentration and adiposity: comparison of young adults in the Philippines and the United States. Am J Clin Nutr 89: 12371245.[Crossref] [Google Scholar]
  20. Thompson AL, Houck KM, Adair L, Gordon-Larsen P, Du S, Zhang B, Popkin B, , 2014. Pathogenic and obesogenic factors associated with inflammation in Chinese children, adolescents and adults. Am J Hum Biol 26: 1828.[Crossref] [Google Scholar]
  21. Kelishadi R, Mirghaffari N, Poursafa P, Gidding SS, , 2009. Lifestyle and environmental factors associated with inflammation, oxidative stress and insulin resistance in children. Atherosclerosis 203: 311319.[Crossref] [Google Scholar]
  22. Shima M, , 2007. Air pollution and serum C-reactive protein concentration in children. J Epidemiol 17: 169176.[Crossref] [Google Scholar]
  23. Fujita M, Brindle E, Lo YJ, Castro P, Cameroamortegui F, , 2014. Nutrient intakes associated with elevated serum C-reactive protein concentrations in normal to underweight breastfeeding women in northern Kenya. Am J Hum Biol 26: 796802.[Crossref] [Google Scholar]
  24. Nazmi A, Oliveira IO, Victora CG, , 2008. Correlates of C-reactive protein levels in young adults: a population-based cohort study of 3827 subjects in Brazil. Braz J Med Biol Res 41: 357367.[Crossref] [Google Scholar]
  25. Oldroyd JC, Heald A, Bansal N, Vyas A, Siddals K, Gibson M, Clayton P, Cruickshank JK, , 2009. Inflammatory markers and growth in south Asian and European origin infants in Britain: the Manchester Children's Growth and Vascular Health Study. Atherosclerosis 207: 227231.[Crossref] [Google Scholar]
  26. Blackwell C, Moscovis S, Hall S, Burns C, Scott RJ, , 2015. Exploring the risk factors for sudden infant deaths and their role in inflammatory responses to infection. Front Immunol 6: 44. [Google Scholar]
  27. Prescott SL, , 2013. Early-life environmental determinants of allergic diseases and the wider pandemic of inflammatory noncommunicable diseases. J Allergy Clin Immunol 131: 2330.[Crossref] [Google Scholar]
  28. Measure DHS Program Instituto Nacional de Estadística, 2009. Encuesta Nacional de Demografiìa y Salud 2008. , eds. La Paz, Bolivia: Ministerio de Salud y Deportes, Instituto Nacional de Estadística. [Google Scholar]
  29. Cuenca AG, Wynn JL, Moldawer LL, Levy O, , 2013. Role of innate immunity in neonatal infection. Am J Perinatol 30: 105112.[Crossref] [Google Scholar]
  30. Erhardt JG, Estes JE, Pfeiffer CM, Biesalski HK, Craft NE, , 2004. Combined measurement of ferritin, soluble transferrin receptor, retinol binding protein, and C-reactive protein by an inexpensive, sensitive, and simple sandwich enzyme-linked immunosorbent assay technique. J Nutr 134: 31273132. [Google Scholar]
  31. World Health Organization (WHO), 2010. WHO Growth Charts. Available at: http://www.cdc.gov/growthcharts/who_charts.htm#. Accessed May 29, 2014. [Google Scholar]
  32. Thurnham DI, Mburu AS, Mwaniki DL, Muniu EM, Alumasa F, de Wagt A, , 2008. Using plasma acute-phase protein concentrations to interpret nutritional biomarkers in apparently healthy HIV-1-seropositive Kenyan adults. Br J Nutr 100: 174182. [Google Scholar]
  33. World Health Organization (WHO) , 2008. Training Course on Child Growth Assessment. Geneva, Switzerland: WHO. [Google Scholar]
  34. Vyas S, Kumaranayake L, , 2006. Constructing socio-economic status indices: how to use principal components analysis. Health Policy Plan 21: 459468.[Crossref] [Google Scholar]
  35. Kleinbaum DG, Klein M, Pryor ER, , 2002. Logistic Regression: A Self-Learning Text. New York, NY: Springer. [Google Scholar]
  36. R Core Team, 2015. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing. [Google Scholar]
  37. Bates D, Maechler M, Bolker B, Walker S, , 2015. Fitting linear mixed-effects models using lme4. J Stat Softw 67: 148.[Crossref] [Google Scholar]
  38. Johnson PC, , 2014. Extension of Nakagawa and Schielzeth's R GLMM 2 to random slopes models. Methods Ecol Evol 5: 944946.[Crossref] [Google Scholar]
  39. Nakagawa S, Schielzeth H, , 2013. A general and simple method for obtaining R 2 from generalized linear mixed-effects models. Methods Ecol Evol 4: 133142.[Crossref] [Google Scholar]
  40. Carey VJ, , 2015. gee: Generalized Estimation Equation Solver. [Google Scholar]
  41. Bertran N, Camps J, Fernandez-Ballart J, Arija V, Ferre N, Tous M, Simo D, Murphy MM, Vilella E, Joven J, , 2005. Diet and lifestyle are associated with serum C-reactive protein concentrations in a population-based study. J Lab Clin Med 145: 4146.[Crossref] [Google Scholar]
  42. Aeberli I, Molinari L, Spinas G, Lehmann R, l'Allemand D, Zimmermann MB, , 2006. Dietary intakes of fat and antioxidant vitamins are predictors of subclinical inflammation in overweight Swiss children. Am J Clin Nutr 84: 748755. [Google Scholar]
  43. Dayal D, Jain H, Attri SV, Bharti B, Bhalla AK, , 2014. Relationship of high sensitivity C-reactive protein levels to anthropometric and other metabolic parameters in Indian children with simple overweight and obesity. J Clin Diagn Res 8: PC05PC08. [Google Scholar]
  44. Lambert M, Delvin EE, Paradis G, O'Loughlin J, Hanley JA, Levy E, , 2004. C-reactive protein and features of the metabolic syndrome in a population-based sample of children and adolescents. Clin Chem 50: 17621768.[Crossref] [Google Scholar]
  45. Lopez-Alcaraz F, Del Toro-Equihua M, Orta-Duarte M, Flores-Ruelas Y, Sanchez-Ramirez CA, , 2014. Higher levels of C-reactive protein associated with higher adiposity in Mexican schoolchildren. Nutr Hosp 29: 531536. [Google Scholar]
  46. Singer K, Eng DS, Lumeng CN, Gebremariam A, Lee MJ, , 2014. The relationship between body fat mass percentiles and inflammation in children. Obesity (Silver Spring) 22: 13321336.[Crossref] [Google Scholar]
  47. Skinner AC, Steiner MJ, Henderson FW, Perrin EM, , 2010. Multiple markers of inflammation and weight status: cross-sectional analyses throughout childhood. Pediatrics 125: e801e809.[Crossref] [Google Scholar]
  48. Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB, , 2001. Low-grade systemic inflammation in overweight children. Pediatrics 107: E13.[Crossref] [Google Scholar]
  49. Cook DG, Mendall MA, Whincup PH, Carey IM, Ballam L, Morris JE, Miller GJ, Strachan DP, , 2000. C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors. Atherosclerosis 149: 139150.[Crossref] [Google Scholar]
  50. Lopez-Jaramillo P, Herrera E, Garcia RG, Camacho PA, Castillo VR, , 2008. Inter-relationships between body mass index, C-reactive protein and blood pressure in a Hispanic pediatric population. Am J Hypertens 21: 527532.[Crossref] [Google Scholar]
  51. Nappo A, Iacoviello L, Fraterman A, Gonzalez-Gil EM, Hadjigeorgiou C, Marild S, Molnar D, Moreno LA, Peplies J, Sioen I, Veidebaum T, Siani A, Russo P, , 2013. High-sensitivity C-reactive protein is a predictive factor of adiposity in children: results of the identification and prevention of dietary- and lifestyle-induced health effects in children and infants (IDEFICS) study. J Am Heart Assoc 2: e000101.[Crossref] [Google Scholar]
  52. Parrett AL, Valentine RJ, Arngrimsson SA, Castelli DM, Evans EM, , 2010. Adiposity, activity, fitness, and C-reactive protein in children. Med Sci Sports Exerc 42: 19811986.[Crossref] [Google Scholar]
  53. Blackwell AD, Snodgrass JJ, Madimenos FC, Sugiyama LS, , 2010. Life history, immune function, and intestinal helminths: trade-offs among immunoglobulin E, C-reactive protein, and growth in an Amazonian population. Am J Hum Biol 22: 836848.[Crossref] [Google Scholar]
  54. Wander K, Brindle E, O'Connor KA, , 2012. Sensitivity and specificity of C-reactive protein and alpha(1)-acid glycoprotein for episodes of acute infection among children in Kilimanjaro, Tanzania. Am J Hum Biol 24: 565568.[Crossref] [Google Scholar]
  55. Garcia OP, Ronquillo D, del Carmen Caamano M, Martinez G, Camacho M, Lopez V, Rosado JL, , 2013. Zinc, iron and vitamins A, C and E are associated with obesity, inflammation, lipid profile and insulin resistance in Mexican school-aged children. Nutrients 5: 50125030.[Crossref] [Google Scholar]
  56. Myers GL, Rifai N, Tracy RP, Roberts WL, Alexander RW, Biasucci LM, Catravas JD, Cole TG, Cooper GR, Khan BV, Kimberly MM, Stein EA, Taubert KA, Warnick GR, Waymack PP, CDC; AHA; , 2004. CDC/AHA workshop on markers of inflammation and cardiovascular disease: application to clinical and public health practice: report from the laboratory science discussion group. Circulation 110: e545e549.[Crossref] [Google Scholar]
  57. Smith SC, Jr Anderson JL, Cannon RO, 3rd Fadl YY, Koenig W, Libby P, Lipshultz SE, Mensah GA, Ridker PM, Rosenson R, CDC; AHA; , 2004. CDC/AHA workshop on markers of inflammation and cardiovascular disease: application to clinical and public health practice: report from the clinical practice discussion group. Circulation 110: e550e553.[Crossref] [Google Scholar]

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  • Received : 14 Apr 2016
  • Accepted : 06 Jul 2016
  • Published online : 05 Oct 2016

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