Victora CG, de Onis M, Hallal PC, Blössner M, Shrimpton R, 2010. Worldwide timing of growth faltering: revisiting implications for interventions. Pediatrics 125: e473–e480.
Hoddinott J, Behrman JR, Maluccio JA, Melgar P, Quisumbing AR, Ramirez-Zea M, Stein AD, Yount KM, Martorell R, 2013. Adult consequences of growth failure in early childhood. Am J Clin Nutr 98: 1170–1178.
Victora CG, 2009. Nutrition in early life: a global priority. Lancet 374: 1123–1125.
Dewey KG, Adu-Afarwuah S, 2008. Systematic review of the efficacy and effectiveness of complementary feeding interventions in developing countries. Matern Child Nutr 4 (Suppl 1): 24–85.
Mata LJ, Kronmal RA, Garcia B, Butler W, Urrutia JJ, Murillo S, 1976. Breast-feeding, weaning and the diarrheal syndrome in a Guatemalan Indian village. Ciba Found Symp 42: 311–338.
Black RE, Brown KH, Becker S, 1984. Effects of diarrhea associated with specific enteropathogens on the growth of children in rural Bangladesh. Pediatrics 73: 799–805.
Guerrant RL, Kirchhoff LV, Shields DS, Nations MK, Leslie J, de Sousa MA, Araujo JG, Correia LL, Sauer KT, McClelland KE, Trowbridge FL, Hughes JM, 1983. Prospective study of diarrheal illnesses in northeastern Brazil: patterns of disease, nutritional impact, etiologies, and risk factors. J Infect Dis 148: 986–997.
Lima AA, Moore SR, Barboza MS, Soares AM, Schleupner MA, Newman RD, Sears CL, Nataro JP, Fedorko DP, Wuhib T, Schorling JB, Guerrant RL, 2000. Persistent diarrhea signals a critical period of increased diarrhea burdens and nutritional shortfalls: a prospective cohort study among children in northeastern Brazil. J Infect Dis 181: 1643–1651.
Moore SR, Lima AA, Conaway MR, Schorling JB, Soares AM, Guerrant RL, 2001. Early childhood diarrhea and helminthiases associate with long-term linear growth faltering. Int J Epidemiol 30: 1457–1464.
Checkley W, Buckley G, Gilman RH, Assis A, Guerrant RL, Morris SS, Molbak K, Valentiner-Branth P, Lanata CF, Black RE; Childhood Malnutrition and Infection Network, 2008. Multi-country analysis of the effects of diarrhea on childhood stunting. Int J Epidemiol 37: 816–830.
Henry FJ, Alam N, Aziz KM, Rahaman MM, 1987. Dysentery, not watery diarrhea, is associated with stunting in Bangladeshi children. Hum Nutr Clin Nutr 41: 243–249.
Briend A, Hasan KZ, Aziz KM, Hoque BA, 1989. Are diarrhea control programmes likely to reduce childhood malnutrition? Observations from rural Bangladesh. Lancet 2: 319–322.
Moy RJ, de C Marshall TF, Choto RG, McNeish AS, Booth IW, 1994. Diarrhea and growth faltering in rural Zimbabwe. Eur J Clin Nutr 48: 810–821.
Brown KH, 2003. Diarrhea and malnutrition. J Nutr 133: 328S–332S.
Stephensen CB, 1999. Burden of infection on growth failure. J Nutr 129: 534–538.
Yakar S, Rosen CJ, Beamer WG, Ackert-Bicknell CL, Wu Y, Liu JL, Ooi GT, Setser J, Frystyk J, Boisclair YR, LeRoith D, 2002. Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest 110: 771–781.
Katsanos KH, Tsatsoulis A, Christodoulou D, Challa A, Katsaraki A, Tsianos EV, 2001. Reduced serum insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 levels in adults with inflammatory bowel disease. Growth Horm IGF Res 11: 364–367.
Walters TD, Griffiths AM, 2009. Mechanisms of growth impairment in pediatric Crohn's disease. Nat Rev Gastroenterol Hepatol 6: 513–523.
Prendergast AJ, Rukobo S, Chasekwa B, Mutasa K, Ntozini R, Mbuya MN, Jones AD, Stoltzfus RJ, Humphrey JH, 2014. Stunting is characterized by chronic inflammation in Zimbabwean infants. PLoS ONE.
Prentice AM, Moore SE, Fulford AJ, 2013. Growth faltering in low-income countries. World Rev Nutr Diet 106: 90–99.
Humphrey JH, Iliff PJ, Marinda ET, Mutasa K, Moulton LH, Chidawanyika H, Ward BJ, Nathoo KJ, Malaba LC, Zijenah LS, Zvandasara P, Ntozini R, Mzengeza F, Mahomva AI, Ruff AJ, Mbizvo MT, Zunguza CD, ZVITAMBO Study Group, 2006. Effects of a single large dose of vitamin A, given during the postpartum period to HIV-positive women and their infants, on child HIV infection, HIV-free survival, and mortality. J Infect Dis 193: 860–871.
Gabay C, Kushner I, 1999. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340: 448–454.
Lieberman JM, Sacchettini J, Marks C, Marks WH, 1997. Human intestinal fatty acid binding protein: report of an assay with studies in normal volunteers and intestinal ischemia. Surgery 121: 335–342.
Gibson RS, 1990. Principles of Nutritional Assessment. New York, NY: Oxford University Press.
Olney DK, Kariger PK, Stoltzfus RJ, Khalfan SS, Ali NS, Tielsch JM, Sazawal S, Black R, Allen LH, Pollitt E, 2009. Development of nutritionally at-risk young children is predicted by malaria, anemia, and stunting in Pemba, Zanzibar. J Nutr 139: 763–772.
MacKinnon DP, Lockwood CM, Hoffman JM, West SG, Sheets V, 2002. A comparison of methods to test mediation and other intervening variable effects. Psychol Methods 7: 83–104.
Baron RM, Kenny DA, 1986. The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol 51: 1173–1182.
Gabay C, Kushner I, 1999. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340: 448–454.
De Benedetti F, Alonzi T, Moretta A, Lazzaro D, Costa P, Poli V, Martini A, Ciliberto G, Fattori E, 1997. Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I. A model for stunted growth in children with chronic inflammation. J Clin Invest 99: 643–650.
Kotloff KL, Blackwelder WC, Nasrin D, Nataro JP, Farag TH, van Eijk A, Adegbola RA, Alonso PL, Breiman RF, Faruque AS, Saha D, Sow SO, Sur D, Zaidi AK, Biswas K, Panchalingam S, Clemens JD, Cohen D, Glass RI, Mintz ED, Sommerfelt H, Levine MM, 2013. Burden and aetiology of diarrheal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382: 209–222.
Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO, 2008. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell 7: 681–687.
Cossack ZT, 1991. Decline in somatomedin-C (insulin-like growth factor-1) with experimentally induced zinc deficiency in human subjects. Clin Nutr 10: 284–291.
Bhutta ZA, Bang P, Karlsson E, Hagenäs L, Nizami SQ, Söder O, 1999. Insulin-like growth factor I response during nutritional rehabilitation of persistent diarrhea. Arch Dis Child 80: 438–442.
Pucilowska JB, Davenport ML, Kabir I, Clemmons DR, Thissen JP, Butler T, Underwood LE, 1993. The effect of dietary protein supplementation on insulin-like growth factors (IGFs) and IGF-binding proteins in children with shigellosis. J Clin Endocrinol Metab 77: 1516–1521.
Kabir I, Butler T, Underwood LE, Rahman MM, 1992. Effects of a protein-rich diet during convalescence from shigellosis on catch-up growth, serum proteins, and insulin-like growth factor-I. Pediatr Res 32: 689–692.
Hintz RL, Suskind R, Amatayakul K, Thanangkul O, Olson R, 1978. Plasma somatomedin and growth hormone values in children with protein-calorie malnutrition. J Pediatr 92: 153–156.
Donahue SP, Phillips LS, 1989. Response of IGF-1 to nutritional support in malnourished hospital patients: a possible indicator of short-term changes in nutritional status. Am J Clin Nutr 50: 962–969.
Soliman AT, Hassan AE, Aref MK, Hintz RL, Rosenfeld RG, Rogol AD, 1986. Serum insulin-like growth factors I and II concentrations and growth hormone and insulin responses to arginine infusion in children with protein-energy malnutrition before and after nutritional rehabilitation. Pediatr Res 20: 1122–1130.
Baricevic I, Nedic O, Nikolic JA, Bojic B, Jojic N, 2004. Circulating insulin-like growth factors in patients infected with Helicobacter pylori. Clin Biochem 37: 997–1001.
Arnold BF, Galiani S, Ram PK, Hubbard AE, Briceno B, Gertler PJ, Colford JM, 2013. Optimal recall period for caregiver-reported illness in risk factor and intervention studies: a multicountry study. Am J Epidemiol 177: 361–370.
Martorell R, Habicht J, Yarbrough C, Lechtig A, Klein R, Western K, 1975. Acute morbidity and physical growth in rural Guatemalan children. Am J Dis Child 129: 1206–1301.
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Frequent infections contribute to childhood stunting in developing countries but the causal pathways are uncertain. We tested the hypothesis that intercurrent illnesses suppress the growth hormone axis through reductions in insulin-like growth factor 1 (IGF-1). In a birth cohort of 202 HIV-unexposed Zimbabwean infants, we analyzed data on 7-day illness recall and measured plasma interleukin-6, C-reactive protein, alpha-1-acid glycoprotein, and IGF-1 by enzyme-linked immunosorbent assay, at age 6 weeks, and then 3, 6, 12, and 18 months. Children with recent acute illness had lower IGF-1 concentrations than healthy children and IGF-1 correlated inversely (P < 0.05) with inflammatory biomarkers at most time points between 3 and 18 months. Using path analysis, we showed that cough and fever had a predominantly indirect effect on suppressing IGF-1, through the acute-phase response, whereas diarrhea had a predominantly direct effect on IGF-1. Acute illness may therefore impact the growth hormone axis through both direct and indirect pathways.
Financial support: This study was funded by the Wellcome Trust (093768/Z/10/Z).
Authors' addresses: Andrew D. Jones, Human Nutrition Program, Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI, E-mail: jonesand@umich.edu. Sandra Rukobo, Bernard Chasekwa, Kuda Mutasa, Robert Ntozini, Mduduzi N. N. Mbuya, and Jean H. Humphrey, Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe, E-mails: srukobo@zvitambo.co.zw, bchasekwa@zvitambo.co.zw, kmutasa@zvitambo.co.zw, rntozini@zvitambo.co.zw, mmbuya@zvitambo.co.zw, and jhumphrey@zvitambo.co.zw. Rebecca J. Stoltzfus, Division of Nutritional Sciences, Cornell University, Ithaca, NY, E-mail: rjs62@cornell.edu. Andrew J. Prendergast, Centre for Paediatrics, Blizard Institute, Queen Mary University of London, London, UK, E-mail: a.prendergast@qmul.ac.uk.
Victora CG, de Onis M, Hallal PC, Blössner M, Shrimpton R, 2010. Worldwide timing of growth faltering: revisiting implications for interventions. Pediatrics 125: e473–e480.
Hoddinott J, Behrman JR, Maluccio JA, Melgar P, Quisumbing AR, Ramirez-Zea M, Stein AD, Yount KM, Martorell R, 2013. Adult consequences of growth failure in early childhood. Am J Clin Nutr 98: 1170–1178.
Victora CG, 2009. Nutrition in early life: a global priority. Lancet 374: 1123–1125.
Dewey KG, Adu-Afarwuah S, 2008. Systematic review of the efficacy and effectiveness of complementary feeding interventions in developing countries. Matern Child Nutr 4 (Suppl 1): 24–85.
Mata LJ, Kronmal RA, Garcia B, Butler W, Urrutia JJ, Murillo S, 1976. Breast-feeding, weaning and the diarrheal syndrome in a Guatemalan Indian village. Ciba Found Symp 42: 311–338.
Black RE, Brown KH, Becker S, 1984. Effects of diarrhea associated with specific enteropathogens on the growth of children in rural Bangladesh. Pediatrics 73: 799–805.
Guerrant RL, Kirchhoff LV, Shields DS, Nations MK, Leslie J, de Sousa MA, Araujo JG, Correia LL, Sauer KT, McClelland KE, Trowbridge FL, Hughes JM, 1983. Prospective study of diarrheal illnesses in northeastern Brazil: patterns of disease, nutritional impact, etiologies, and risk factors. J Infect Dis 148: 986–997.
Lima AA, Moore SR, Barboza MS, Soares AM, Schleupner MA, Newman RD, Sears CL, Nataro JP, Fedorko DP, Wuhib T, Schorling JB, Guerrant RL, 2000. Persistent diarrhea signals a critical period of increased diarrhea burdens and nutritional shortfalls: a prospective cohort study among children in northeastern Brazil. J Infect Dis 181: 1643–1651.
Moore SR, Lima AA, Conaway MR, Schorling JB, Soares AM, Guerrant RL, 2001. Early childhood diarrhea and helminthiases associate with long-term linear growth faltering. Int J Epidemiol 30: 1457–1464.
Checkley W, Buckley G, Gilman RH, Assis A, Guerrant RL, Morris SS, Molbak K, Valentiner-Branth P, Lanata CF, Black RE; Childhood Malnutrition and Infection Network, 2008. Multi-country analysis of the effects of diarrhea on childhood stunting. Int J Epidemiol 37: 816–830.
Henry FJ, Alam N, Aziz KM, Rahaman MM, 1987. Dysentery, not watery diarrhea, is associated with stunting in Bangladeshi children. Hum Nutr Clin Nutr 41: 243–249.
Briend A, Hasan KZ, Aziz KM, Hoque BA, 1989. Are diarrhea control programmes likely to reduce childhood malnutrition? Observations from rural Bangladesh. Lancet 2: 319–322.
Moy RJ, de C Marshall TF, Choto RG, McNeish AS, Booth IW, 1994. Diarrhea and growth faltering in rural Zimbabwe. Eur J Clin Nutr 48: 810–821.
Brown KH, 2003. Diarrhea and malnutrition. J Nutr 133: 328S–332S.
Stephensen CB, 1999. Burden of infection on growth failure. J Nutr 129: 534–538.
Yakar S, Rosen CJ, Beamer WG, Ackert-Bicknell CL, Wu Y, Liu JL, Ooi GT, Setser J, Frystyk J, Boisclair YR, LeRoith D, 2002. Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest 110: 771–781.
Katsanos KH, Tsatsoulis A, Christodoulou D, Challa A, Katsaraki A, Tsianos EV, 2001. Reduced serum insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 levels in adults with inflammatory bowel disease. Growth Horm IGF Res 11: 364–367.
Walters TD, Griffiths AM, 2009. Mechanisms of growth impairment in pediatric Crohn's disease. Nat Rev Gastroenterol Hepatol 6: 513–523.
Prendergast AJ, Rukobo S, Chasekwa B, Mutasa K, Ntozini R, Mbuya MN, Jones AD, Stoltzfus RJ, Humphrey JH, 2014. Stunting is characterized by chronic inflammation in Zimbabwean infants. PLoS ONE.
Prentice AM, Moore SE, Fulford AJ, 2013. Growth faltering in low-income countries. World Rev Nutr Diet 106: 90–99.
Humphrey JH, Iliff PJ, Marinda ET, Mutasa K, Moulton LH, Chidawanyika H, Ward BJ, Nathoo KJ, Malaba LC, Zijenah LS, Zvandasara P, Ntozini R, Mzengeza F, Mahomva AI, Ruff AJ, Mbizvo MT, Zunguza CD, ZVITAMBO Study Group, 2006. Effects of a single large dose of vitamin A, given during the postpartum period to HIV-positive women and their infants, on child HIV infection, HIV-free survival, and mortality. J Infect Dis 193: 860–871.
Gabay C, Kushner I, 1999. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340: 448–454.
Lieberman JM, Sacchettini J, Marks C, Marks WH, 1997. Human intestinal fatty acid binding protein: report of an assay with studies in normal volunteers and intestinal ischemia. Surgery 121: 335–342.
Gibson RS, 1990. Principles of Nutritional Assessment. New York, NY: Oxford University Press.
Olney DK, Kariger PK, Stoltzfus RJ, Khalfan SS, Ali NS, Tielsch JM, Sazawal S, Black R, Allen LH, Pollitt E, 2009. Development of nutritionally at-risk young children is predicted by malaria, anemia, and stunting in Pemba, Zanzibar. J Nutr 139: 763–772.
MacKinnon DP, Lockwood CM, Hoffman JM, West SG, Sheets V, 2002. A comparison of methods to test mediation and other intervening variable effects. Psychol Methods 7: 83–104.
Baron RM, Kenny DA, 1986. The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol 51: 1173–1182.
Gabay C, Kushner I, 1999. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340: 448–454.
De Benedetti F, Alonzi T, Moretta A, Lazzaro D, Costa P, Poli V, Martini A, Ciliberto G, Fattori E, 1997. Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I. A model for stunted growth in children with chronic inflammation. J Clin Invest 99: 643–650.
Kotloff KL, Blackwelder WC, Nasrin D, Nataro JP, Farag TH, van Eijk A, Adegbola RA, Alonso PL, Breiman RF, Faruque AS, Saha D, Sow SO, Sur D, Zaidi AK, Biswas K, Panchalingam S, Clemens JD, Cohen D, Glass RI, Mintz ED, Sommerfelt H, Levine MM, 2013. Burden and aetiology of diarrheal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382: 209–222.
Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO, 2008. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell 7: 681–687.
Cossack ZT, 1991. Decline in somatomedin-C (insulin-like growth factor-1) with experimentally induced zinc deficiency in human subjects. Clin Nutr 10: 284–291.
Bhutta ZA, Bang P, Karlsson E, Hagenäs L, Nizami SQ, Söder O, 1999. Insulin-like growth factor I response during nutritional rehabilitation of persistent diarrhea. Arch Dis Child 80: 438–442.
Pucilowska JB, Davenport ML, Kabir I, Clemmons DR, Thissen JP, Butler T, Underwood LE, 1993. The effect of dietary protein supplementation on insulin-like growth factors (IGFs) and IGF-binding proteins in children with shigellosis. J Clin Endocrinol Metab 77: 1516–1521.
Kabir I, Butler T, Underwood LE, Rahman MM, 1992. Effects of a protein-rich diet during convalescence from shigellosis on catch-up growth, serum proteins, and insulin-like growth factor-I. Pediatr Res 32: 689–692.
Hintz RL, Suskind R, Amatayakul K, Thanangkul O, Olson R, 1978. Plasma somatomedin and growth hormone values in children with protein-calorie malnutrition. J Pediatr 92: 153–156.
Donahue SP, Phillips LS, 1989. Response of IGF-1 to nutritional support in malnourished hospital patients: a possible indicator of short-term changes in nutritional status. Am J Clin Nutr 50: 962–969.
Soliman AT, Hassan AE, Aref MK, Hintz RL, Rosenfeld RG, Rogol AD, 1986. Serum insulin-like growth factors I and II concentrations and growth hormone and insulin responses to arginine infusion in children with protein-energy malnutrition before and after nutritional rehabilitation. Pediatr Res 20: 1122–1130.
Baricevic I, Nedic O, Nikolic JA, Bojic B, Jojic N, 2004. Circulating insulin-like growth factors in patients infected with Helicobacter pylori. Clin Biochem 37: 997–1001.
Arnold BF, Galiani S, Ram PK, Hubbard AE, Briceno B, Gertler PJ, Colford JM, 2013. Optimal recall period for caregiver-reported illness in risk factor and intervention studies: a multicountry study. Am J Epidemiol 177: 361–370.
Martorell R, Habicht J, Yarbrough C, Lechtig A, Klein R, Western K, 1975. Acute morbidity and physical growth in rural Guatemalan children. Am J Dis Child 129: 1206–1301.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 1200 | 997 | 41 |
Full Text Views | 390 | 16 | 2 |
PDF Downloads | 134 | 16 | 0 |