Stunting is characterized by chronic inflammation in Zimbabwean infants

• Published in: PloS one Vol. 9; no. 2; p. e86928
• Main Authors: Prendergast, Andrew J, Rukobo, Sandra, Chasekwa, Bernard, Mutasa, Kuda, Ntozini, Robert, Mbuya, Mduduzi N N, Jones, Andrew, Moulton, Lawrence H, Stoltzfus, Rebecca J, Humphrey, Jean H
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.02.2014; Public Library of Science (PLoS)
• Subjects: Age; Analysis; Anthropometry; Babies; Biology; Biomarkers; Biomarkers - blood; Biomarkers - metabolism; Birth; C-Reactive Protein - metabolism; Case-Control Studies; Celiac disease; Child, Preschool; Childbirth & labor; Children; Children & youth; Childrens health; Developing countries; Fatty acid-binding protein; Female; Growth Disorders - epidemiology; Growth hormone; Health risk assessment; Heat affected zone; HIV; HIV Infections - blood; HIV Infections - diagnosis; Human Growth Hormone - metabolism; Human immunodeficiency virus; Humans; Hygiene; Infants; Inflammation; Inflammation - epidemiology; Inflammation - physiopathology; Insulin-Like Growth Factor Binding Protein 3 - blood; Insulin-like growth factor I; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factor-binding protein 3; Interleukin 6; Interleukin-6 - blood; Intestine; LDCs; Male; Medical research; Medicine; Models, Statistical; Multivariate Analysis; Nutrition; Obesity; Odds Ratio; Permeability; Public health; Quality; Regression analysis; Regression models; Sanitation; Somatotropin; Studies; Zimbabwe - epidemiology; Zimbabwe; United States > US; Maryland; Baltimore Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0086928

Stunting affects one-third of children in developing countries, but the causes remain unclear. We hypothesized that enteropathy leads to low-grade inflammation, which suppresses the growth hormone-IGF axis and mediates stunting. We conducted a case-control study of 202 HIV-unexposed Zimbabwean infants who were stunted (height-for-age Z-score (HAZ) <-2; cases) or non-stunted (HAZ >-0.5; controls) at 18 months. We measured biomarkers of intestinal damage (I-FABP), inflammation (CRP, AGP, IL-6) and growth hormone-IGF axis (IGF-1, IGFBP3) in infant plasma at 6 weeks and 3, 6, 12 and 18 months, and in paired maternal-infant plasma at birth. Adjusted mean differences between biomarkers were estimated using regression models. Multivariate odds ratios of stunting were estimated by logistic regression. At birth, cases were shorter (median (IQR) HAZ -1.00 (-1.53, -0.08) vs 0.03 (-0.57, 0.62,); P<0.001) than controls and their mothers had lower levels of IGF-1 (adjusted mean difference (95%CI) -21.4 (-39.8, -3.1) ng/mL). From 6 weeks to 12 months of age, levels of CRP and AGP were consistently higher and IGF-1 and IGFBP3 lower in cases versus controls; IGF-1 correlated inversely with inflammatory markers at all time-points. I-FABP increased between 3-12 months, indicating extensive intestinal damage during infancy, which was similar in cases and controls. In multivariate analysis, higher log10 levels of CRP (aOR 3.06 (95%CI 1.34, 6.99); P = 0.008) and AGP (aOR 7.87 (95%CI 0.74, 83.74); P = 0.087) during infancy were associated with stunting. There were no associations between levels of I-FABP, IL-6, sCD14 or EndoCAb and stunting. Stunting began in utero and was associated with low maternal IGF-1 levels at birth. Inflammatory markers were higher in cases than controls from 6 weeks of age and were associated with lower levels of IGF-1 throughout infancy. Higher levels of CRP and AGP during infancy were associated with stunting. These findings suggest that an extensive enteropathy occurs during infancy and that low-grade chronic inflammation may impair infant growth.