Stunting is characterized by chronic inflammation in Zimbabwean infants.

<h4>Background</h4>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.<h4>Methods</h4>We conducted...

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Main Authors: Andrew J Prendergast, Sandra Rukobo, Bernard Chasekwa, Kuda Mutasa, Robert Ntozini, Mduduzi N N Mbuya, Andrew Jones, Lawrence H Moulton, Rebecca J Stoltzfus, Jean H Humphrey
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0086928&type=printable
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author Andrew J Prendergast
Sandra Rukobo
Bernard Chasekwa
Kuda Mutasa
Robert Ntozini
Mduduzi N N Mbuya
Andrew Jones
Lawrence H Moulton
Rebecca J Stoltzfus
Jean H Humphrey
author_facet Andrew J Prendergast
Sandra Rukobo
Bernard Chasekwa
Kuda Mutasa
Robert Ntozini
Mduduzi N N Mbuya
Andrew Jones
Lawrence H Moulton
Rebecca J Stoltzfus
Jean H Humphrey
author_sort Andrew J Prendergast
collection DOAJ
description <h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
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spelling doaj-art-22ab9145ff854a37a828d8dccb3afcd62025-08-20T03:10:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8692810.1371/journal.pone.0086928Stunting is characterized by chronic inflammation in Zimbabwean infants.Andrew J PrendergastSandra RukoboBernard ChasekwaKuda MutasaRobert NtoziniMduduzi N N MbuyaAndrew JonesLawrence H MoultonRebecca J StoltzfusJean H Humphrey<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0086928&type=printable
spellingShingle Andrew J Prendergast
Sandra Rukobo
Bernard Chasekwa
Kuda Mutasa
Robert Ntozini
Mduduzi N N Mbuya
Andrew Jones
Lawrence H Moulton
Rebecca J Stoltzfus
Jean H Humphrey
Stunting is characterized by chronic inflammation in Zimbabwean infants.
PLoS ONE
title Stunting is characterized by chronic inflammation in Zimbabwean infants.
title_full Stunting is characterized by chronic inflammation in Zimbabwean infants.
title_fullStr Stunting is characterized by chronic inflammation in Zimbabwean infants.
title_full_unstemmed Stunting is characterized by chronic inflammation in Zimbabwean infants.
title_short Stunting is characterized by chronic inflammation in Zimbabwean infants.
title_sort stunting is characterized by chronic inflammation in zimbabwean infants
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0086928&type=printable
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