title: Correlates of thymus size and changes during treatment of children with severe acute malnutrition: a cohort study.
abstract: The impairment of immune functions associated with malnutrition may be one reason for the high mortality in children with severe acute malnutrition (SAM), and thymus atrophy has been proposed as a marker of this immunodeficiency. The aim of this study was to identify nutritional and clinical correlates of thymus size in children with SAM, and predictors of change in thymus size with nutritional rehabilitation.
  
  
  
  In an observational study among children aged 6-59 months admitted with SAM in Uganda, we measured thymus area by ultrasound on hospital admission to treatment with F75 and F100, on hospital discharge and after 8 weeks of nutritional rehabilitation with ready-to-use therapeutic food, as well as in well-nourished healthy children. We investigated anthropometric, clinical, biochemical and treatment-related correlates of area and growth of the thymus.
  
  
  
  Eighty-five children with SAM with a median age of 16.5 months were included. On admission 27% of the children had a thymus undetectable by ultrasound. Median thymus area was 1.3 cm2in malnourished children, and 3.5 cm2in healthy children (p < 0.001). Most anthropometric z-scores, hemoglobin and plasma phosphate correlated positively with thymus area. Thymus area correlated negatively with caretaker-reported severity of illness, plasma α-1 acid glycoprotein, and C-reactive protein >5 mg/L. At follow-up after 8 weeks, median thymus area had increased to 2.5 cm2(p < 0.001). Increase in thymus area during treatment was associated with simultaneous increase in mid-upper-arm circumference, with 0.29 cm2higher increase in thymus area per cm larger increment in MUAC (p = 0.03). Children whose F-75 had partially been replaced by rice porridge during their hospital admission had less increase in thymus area after 8 weeks.
  
  
  
  Malnutrition and inflammation are associated with thymus atrophy, and thymus area seems positively associated with plasma phosphate. Substituting therapeutic formula with unfortified rice porridge with the aim of alleviating diarrhea may impair regain of thymus size with nutritional rehabilitation. This calls for research into possible effects of phosphate status on thymus size and other immunological markers.
  
  
  
  The study is based on data from the FeedSAM study, ISRCTN55092738 .
authors.affiliation: Department of Nutrition, Exercise and Sports, University of Copenhagen, Rolighedsvej 30, 1958, Frederiksberg C, Denmark. marenrytter@hotmail.com.
authors.forename: Maren Johanne Heilskov
authors.initials: MJ
authors.lastname: Rytter
authors.affiliation: Mwanamugimu Nutrition Unit, Mulago Hospital, Kampala, Uganda.
authors.forename: Hanifa
authors.initials: H
authors.lastname: Namusoke
authors.affiliation: Department of Nutrition, Exercise and Sports, University of Copenhagen, Rolighedsvej 30, 1958, Frederiksberg C, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Ritz
authors.affiliation: Department of Nutrition, Exercise and Sports, University of Copenhagen, Rolighedsvej 30, 1958, Frederiksberg C, Denmark.
authors.forename: Kim F
authors.initials: KF
authors.lastname: Michaelsen
authors.affiliation: Department of Nutrition, Exercise and Sports, University of Copenhagen, Rolighedsvej 30, 1958, Frederiksberg C, Denmark.|Tampere Centre for Child Health Research, University of Tampere, Tampere, Finland.
authors.forename: André
authors.initials: A
authors.lastname: Briend
authors.affiliation: Department of Nutrition, Exercise and Sports, University of Copenhagen, Rolighedsvej 30, 1958, Frederiksberg C, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Friis
authors.affiliation: Department of Pediatrics, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark.
authors.forename: Dorthe
authors.initials: D
authors.lastname: Jeppesen
mesh_terms: D001284:Atrophy; D016022:Case-Control Studies; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization; D006801:Humans; D007223:Infant; D008297:Male; D044623:Nutrition Therapy / Q000379:methods*; D009929:Organ Size; D000067011:Severe Acute Malnutrition / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology* / Q000534:rehabilitation; D013950:Thymus Gland / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology*; D016896:Treatment Outcome; D014454:Uganda; D014463:Ultrasonography
keywords: Electrolytes; Immune function; Inflammation; Phosphate; Re-feeding; Thymus; Undernutrition