title: Serum retinol concentrations demonstrate high specificity after correcting for inflammation but questionable sensitivity compared with liver stores calculated from isotope dilution in determining vitamin A deficiency in Thai and Zambian children.
abstract: BACKGROUND
  The WHO estimates that 190 million preschool children have vitamin A deficiency (VAD). Serum retinol (SR) concentration is a common indicator of vitamin A (VA) status, but SR is homeostatically controlled and suppressed during inflammation, which may lead to misdiagnosis.
  
  
  OBJECTIVE
  The sensitivity and specificity of SR compared with VA total liver reserves (TLRs) were evaluated for VAD in children from Thailand (n = 37) and Zambia (n = 128). SR was adjusted for inflammation in the Zambian children.
  
  
  METHODS
  Each child was classified as VA-deficient or not based on cutoffs of <0.1 μmol VA/g liver with the use of retinol isotope dilution and <0.7 μmol/L for SR concentrations. Four categories of infection status in the Zambian children were based on elevated C-reactive protein (CRP) and α1-acid glycoprotein (AGP). Sensitivity and specificity were calculated with the use of unadjusted and inflammation marker-adjusted SR cutoffs.
  
  
  RESULTS
  VAD was 65% and 0% according to TLRs and SR, respectively, in Thai children and 0% and 17%, respectively, in Zambian children. No true positive VAD cases occurred; thus, sensitivity was 0% and indeterminable, respectively; specificity was 100% and 82.8%, respectively. CRP was elevated in 26.6% of Zambian children, whereas 97.7% had elevated AGP, categorizing them as having no infection (2.3%) or in early (26.6%) or late (58.6%) convalescence. With the use of marker-adjusted SR cutoffs of 0.6 μmol/L for late convalescence and 0.5 μmol/L for early convalescence, the adjusted prevalence of SR deficiency was 2.3%, increasing specificity to 97.3%.
  
  
  CONCLUSIONS
  No cases of VAD were identified by both TLRs and SR (true positives) in Thai or Zambian children. Specificity of SR to evaluate VAD was high, but additional research is needed to investigate sensitivity. Adjusting SR cutoffs for inflammation improved specificity by reducing false positives. SR as a VAD indicator may depend on infection rates, which should be taken into consideration. These studies were registered at clinicaltrials.gov as NCT01061307 (for Thailand) and NCT01814891 (for Zambia).
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI;
authors.forename: Devika J
authors.initials: DJ
authors.lastname: Suri
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI;
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Tanumihardjo
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI;
authors.forename: Bryan M
authors.initials: BM
authors.lastname: Gannon
authors.affiliation: Department of Food Science and Nutrition, Faculty of Science and Technology, Prince of Songkla University, Pattani, Thailand;
authors.forename: Siwaporn
authors.initials: S
authors.lastname: Pinkaew
authors.affiliation: National Food and Nutrition Commission of Zambia, Lusaka, Zambia; and.
authors.forename: Chisela
authors.initials: C
authors.lastname: Kaliwile
authors.affiliation: Tropical Diseases Research Centre, Ndola, Zambia.
authors.forename: Justin
authors.initials: J
authors.lastname: Chileshe
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI; sherry@nutrisci.wisc.edu.
authors.forename: Sherry A
authors.initials: SA
authors.lastname: Tanumihardjo
mesh_terms: D000465:Algorithms; D002097:C-Reactive Protein / Q000032:analysis; D002247:Carbon Isotopes; D002648:Child; D002664:Child Nutritional Physiological Phenomena; D002675:Child, Preschool; D004224:Diterpenes; D005260:Female; D006801:Humans; D007201:Indicator Dilution Techniques; D018836:Inflammation Mediators / Q000097:blood*; D008099:Liver / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009752:Nutritional Status; D009961:Orosomucoid / Q000032:analysis; D015995:Prevalence; D000084562:Retinyl Esters; D012423:Rural Health; D012680:Sensitivity and Specificity; D013785:Thailand / Q000453:epidemiology; D014801:Vitamin A / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism; D014802:Vitamin A Deficiency / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology; D015024:Zambia / Q000453:epidemiology
chemical_list: D002247:Carbon Isotopes; D004224:Diterpenes; D018836:Inflammation Mediators; D009961:Orosomucoid; D000084562:Retinyl Esters; D014801:Vitamin A; C009166:retinol acetate; D002097:C-Reactive Protein
keywords: Thailand; Zambia; school-age children; stable isotope dilution; vitamin A deficiency