title: Systemic inflammation, growth factors, and linear growth in the setting of infection and malnutrition.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pediatric Endocrinology, Department of Pediatrics, University of Virginia, Charlottesville, VA. Electronic address: deboer@virginia.edu.
authors.forename: Mark D
authors.initials: MD
authors.lastname: DeBoer
authors.affiliation: Developmental Pediatrics, Department of Pediatrics, University of Virginia, Charlottesville, VA.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Scharf
authors.affiliation: Institute of Biomedicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Alvaro M
authors.initials: AM
authors.lastname: Leite
authors.affiliation: Institute of Biomedicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Férrer
authors.affiliation: Institute of Biomedicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Havt
authors.affiliation: Center for Global Health, University of Virginia, Charlottesville, VA.
authors.forename: Relana
authors.initials: R
authors.lastname: Pinkerton
authors.affiliation: Institute of Biomedicine, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Aldo A
authors.initials: AA
authors.lastname: Lima
authors.affiliation: Center for Global Health, University of Virginia, Charlottesville, VA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Guerrant
mesh_terms: D015415:Biomarkers / Q000097:blood; D001827:Body Height; D001938:Brazil / Q000453:epidemiology; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006130:Growth Disorders / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D007223:Infant; D007227:Infant Nutritional Physiological Phenomena; D007239:Infections / Q000150:complications* / Q000276:immunology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D008297:Male; D044342:Malnutrition / Q000097:blood / Q000150:complications* / Q000276:immunology / Q000503:physiopathology; D009752:Nutritional Status; D011203:Poverty; D015995:Prevalence; D013851:Thinness / Q000453:epidemiology / Q000209:etiology; D019282:Wasting Syndrome / Q000453:epidemiology / Q000209:etiology*
chemical_list: D015415:Biomarkers; C035170:IGF2 protein, human; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D007335:Insulin-Like Growth Factor II; D002097:C-Reactive Protein
keywords: Diarrhea; Growth; IGF-1; Nutrition; Stunting