Limits...
Stunting is characterized by chronic inflammation in Zimbabwean infants.

Prendergast AJ, Rukobo S, Chasekwa B, Mutasa K, Ntozini R, Mbuya MN, Jones A, Moulton LH, Stoltzfus RJ, Humphrey JH - PLoS ONE (2014)

Bottom Line: I-FABP increased between 3-12 months, indicating extensive intestinal damage during infancy, which was similar in cases and controls.Inflammatory markers were higher in cases than controls from 6 weeks of age and were associated with lower levels of IGF-1 throughout infancy.These findings suggest that an extensive enteropathy occurs during infancy and that low-grade chronic inflammation may impair infant growth.

View Article: PubMed Central - PubMed

Affiliation: Centre for Paediatrics, Blizard Institute, Queen Mary University of London, London, United Kingdom ; Zvitambo Institute for Maternal Child Health Research, Harare, Zimbabwe ; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.

ABSTRACT

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Show MeSH

Related in: MedlinePlus

Changes in biomarkers over the first 18 months of life.Levels of A: Insulin-like growth factor 1 (IGF-1), B: IGF-binding protein 3 (IGFBP3), C: Intestinal fatty acid binding protein (I-FABP), D: Soluble CD14 (sCD14), E: IgG endotoxin core antibodies (EndoCAb), F: Interleukin-6 (IL-6), G: C-reactive protein (CRP) and H: Alpha-1 acid glycoprotein (AGP), in non-stunted (blue line) and stunted (red line) infants between birth and 18 months of age. Data shown are means with standard errors, except for IL-6, which shows medians with interquartile range (solid error bars for non-stunted infants and dashed bars for stunted infants). Mean levels, standard deviations, unadjusted and adjusted differences between cases and controls are shown in Table S1.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3928146&req=5

pone-0086928-g003: Changes in biomarkers over the first 18 months of life.Levels of A: Insulin-like growth factor 1 (IGF-1), B: IGF-binding protein 3 (IGFBP3), C: Intestinal fatty acid binding protein (I-FABP), D: Soluble CD14 (sCD14), E: IgG endotoxin core antibodies (EndoCAb), F: Interleukin-6 (IL-6), G: C-reactive protein (CRP) and H: Alpha-1 acid glycoprotein (AGP), in non-stunted (blue line) and stunted (red line) infants between birth and 18 months of age. Data shown are means with standard errors, except for IL-6, which shows medians with interquartile range (solid error bars for non-stunted infants and dashed bars for stunted infants). Mean levels, standard deviations, unadjusted and adjusted differences between cases and controls are shown in Table S1.

Mentions: To test our hypothesis that stunting arises due to suppression of the growth hormone-IGF axis during infancy, we measured IGF-1 levels at each time-point between birth and 18 mo. IGF-1 levels at birth were similar in cases and controls, but from 6 weeks of age IGF-1 was significantly lower in cases than controls (adjusted mean difference (95%CI) −10.5 (−15.7, −5.3) ng/mL; Table S1). IGF-1 kinetics showed a similar pattern between groups (Fig. 3A), with an initial increase between birth and 3 mo followed by a progressive decline to 18 mo of age, when concentrations became similar in cases and controls (adjusted mean difference (95%CI) 2.0 (−2.4, 6.5) ng/mL; Table S1).


Stunting is characterized by chronic inflammation in Zimbabwean infants.

Prendergast AJ, Rukobo S, Chasekwa B, Mutasa K, Ntozini R, Mbuya MN, Jones A, Moulton LH, Stoltzfus RJ, Humphrey JH - PLoS ONE (2014)

Changes in biomarkers over the first 18 months of life.Levels of A: Insulin-like growth factor 1 (IGF-1), B: IGF-binding protein 3 (IGFBP3), C: Intestinal fatty acid binding protein (I-FABP), D: Soluble CD14 (sCD14), E: IgG endotoxin core antibodies (EndoCAb), F: Interleukin-6 (IL-6), G: C-reactive protein (CRP) and H: Alpha-1 acid glycoprotein (AGP), in non-stunted (blue line) and stunted (red line) infants between birth and 18 months of age. Data shown are means with standard errors, except for IL-6, which shows medians with interquartile range (solid error bars for non-stunted infants and dashed bars for stunted infants). Mean levels, standard deviations, unadjusted and adjusted differences between cases and controls are shown in Table S1.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928146&req=5

pone-0086928-g003: Changes in biomarkers over the first 18 months of life.Levels of A: Insulin-like growth factor 1 (IGF-1), B: IGF-binding protein 3 (IGFBP3), C: Intestinal fatty acid binding protein (I-FABP), D: Soluble CD14 (sCD14), E: IgG endotoxin core antibodies (EndoCAb), F: Interleukin-6 (IL-6), G: C-reactive protein (CRP) and H: Alpha-1 acid glycoprotein (AGP), in non-stunted (blue line) and stunted (red line) infants between birth and 18 months of age. Data shown are means with standard errors, except for IL-6, which shows medians with interquartile range (solid error bars for non-stunted infants and dashed bars for stunted infants). Mean levels, standard deviations, unadjusted and adjusted differences between cases and controls are shown in Table S1.
Mentions: To test our hypothesis that stunting arises due to suppression of the growth hormone-IGF axis during infancy, we measured IGF-1 levels at each time-point between birth and 18 mo. IGF-1 levels at birth were similar in cases and controls, but from 6 weeks of age IGF-1 was significantly lower in cases than controls (adjusted mean difference (95%CI) −10.5 (−15.7, −5.3) ng/mL; Table S1). IGF-1 kinetics showed a similar pattern between groups (Fig. 3A), with an initial increase between birth and 3 mo followed by a progressive decline to 18 mo of age, when concentrations became similar in cases and controls (adjusted mean difference (95%CI) 2.0 (−2.4, 6.5) ng/mL; Table S1).

Bottom Line: I-FABP increased between 3-12 months, indicating extensive intestinal damage during infancy, which was similar in cases and controls.Inflammatory markers were higher in cases than controls from 6 weeks of age and were associated with lower levels of IGF-1 throughout infancy.These findings suggest that an extensive enteropathy occurs during infancy and that low-grade chronic inflammation may impair infant growth.

View Article: PubMed Central - PubMed

Affiliation: Centre for Paediatrics, Blizard Institute, Queen Mary University of London, London, United Kingdom ; Zvitambo Institute for Maternal Child Health Research, Harare, Zimbabwe ; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.

ABSTRACT

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Show MeSH
Related in: MedlinePlus