Acute illness is associated with suppression of the growth hormone axis in Zimbabwean infants

Abstract

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.

Figure 1.

Path diagram showing hypothesized direct and indirect effects of recent acute illness on the growth hormone axis with mediation by inflammation. Path coefficients are shown to illustrate the relationships between the variables in the path model. The coefficients are for the relationships between recent fever, alpha-1-acid glycoprotein (AGP) and insulin-like growth factor 1 (IGF-1) at 3 mo (Table 2).

Figure 2.

Relationships between report of child recent acute illness and inflammatory markers. Mean estimates at each time point are shown together with error bars representing standard errors (SE). The top, middle, and lower panels show data for report of diarrhea, cough, and fever, respectively. P values are for differences in biomarker concentrations at each time point between children with reported recent illness versus no reported recent illness: ***P < 0.001, **P < 0.01, *P < 0.05.

Figure 3.

Relationships between report of recent acute illness and plasma insulin-like growth factor 1. Mean estimates at each time point are shown together with error bars representing standard errors (SE). The left, middle, and right panels show data for report of diarrhea, cough, and fever, respectively. P values are for differences in biomarker concentrations at each time point between children with reported recent illness versus no reported recent illness: ***P < 0.001, **P < 0.01, *P < 0.05.