Systemic inflammation, growth factors, and linear growth in the setting of infection and malnutrition

TLDR

Deficits in weight gain and linear growth are common among children in malnutrition‑ and infection‑prone settings, yet the interplay between infection, inflammation, and growth deficits remains unclear. The study evaluated relationships between systemic inflammation, growth factors, and anthropometry in 147 underweight and normal‑weight children aged 6–24 months in northern Brazil’s MAL‑ED case‑control cohort. Nonparametric tests and linear regression were used to assess associations among infection symptoms, high‑sensitivity C‑reactive protein, the GH–IGF‑1 axis, and anthropometric measures. Children with recent infections showed elevated hsCRP and GH resistance, while IGF‑1 and IGFBP‑3 levels were positively linked to height and weight z‑scores independent of hsCRP, underscoring complex interactions among infection, inflammation, the GH axis, and linear growth.

Abstract

Deficits in weight gain and linear growth are seen frequently among children in areas where malnutrition and recurrent infections are common. Although both inflammation and malnutrition can result in growth hormone (GH) resistance, the interrelationships of infection, inflammation, and growth deficits in developing areas remain unclear. The aim of this study was to evaluate relationships between low levels of systemic inflammation, growth factors, and anthropometry in a case-control cohort of underweight and normal weight children in northern Brazil.We evaluated data from 147 children ages 6 to 24 mo evaluated in the MAL-ED (Interactions of Malnutrition and Enteric Disease) case-control study following recruitment from a nutrition clinic for impoverished families in Fortaleza, Brazil. We used nonparametric tests and linear regression to evaluate relationships between current symptoms of infections (assessed by questionnaire), systemic inflammation (assessed by high-sensitivity C-reactive protein [hsCRP]), the GH insulin-like growth factor-1 (IGF-1) axis, and measures of anthropometry. All models were adjusted for age and sex.Children with recent symptoms of diarrhea, cough, and fever (compared with those without symptoms) had higher hsCRP levels; those with recent diarrhea and fever also had lower IGF-1 and higher GH levels. Stool myeloperoxidase was positively associated with serum hsCRP. hsCRP was in turn positively associated with GH and negatively associated with IGF-1 and IGF-binding protein-3 (IGFBP-3), suggesting a state of GH resistance. After adjustment for hsCRP, IGF-1 and IGFBP-3 were positively and GH was negatively associated with Z scores for height and weight.Infection and inflammation were linked to evidence of GH resistance, whereas levels of GH, IGF-1, and IGFBP-3 were associated with growth indices independent of hsCRP. These data implicate complex interrelationships between infection, nutritional status, GH axis, and linear growth in children from a developing area.