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Published on: June 24, 2020
Stunting is characterized by chronic inflammation in Zimbabwean infants
Andrew J Prendergast1, Sandra Rukobo2, Bernard Chasekwa2
1Centre 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.
Insights
Child stunting in developing countries is linked to inflammation and impaired growth. Early life inflammation, indicated by CRP and AGP, is associated with stunting, suggesting a chronic inflammatory process affecting infant growth.
Area of Science:
- Pediatric Nutrition and Growth
- Developmental Pediatrics
- Global Child Health
Background:
- Stunting affects one-third of children in developing nations, with unclear causes.
- A hypothesis suggests enteropathy leads to low-grade inflammation, suppressing the growth hormone-IGF axis and causing stunting.
Purpose of the Study:
- To investigate the relationship between enteropathy, inflammation, the growth hormone-IGF axis, and stunting in Zimbabwean infants.
- To identify early life biomarkers associated with stunting.
Main Methods:
- A case-control study of 202 infants (stunted vs. non-stunted) at 18 months.
- Plasma biomarkers of intestinal damage (I-FABP), inflammation (CRP, AGP, IL-6), and growth hormone-IGF axis (IGF-1, IGFBP3) were measured from birth to 18 months.
- Regression models were used to analyze biomarker differences and logistic regression for stunting risk.
Main Results:
- Stunted infants had lower maternal IGF-1 at birth and consistently higher inflammatory markers (CRP, AGP) and lower IGF-1/IGFBP3 from 6 weeks to 12 months.
- Infant IGF-1 correlated inversely with inflammatory markers.
- Higher CRP and AGP levels during infancy were associated with stunting, while I-FABP levels were similar between groups.
Conclusions:
- Stunting originates in utero, associated with maternal IGF-1 levels.
- Low-grade chronic inflammation, indicated by elevated CRP and AGP from early infancy, is linked to stunting.
- Enteropathy during infancy may contribute to chronic inflammation, impairing growth.
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.
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