Baseline Hemoglobin, Hepcidin, Ferritin, and Total Body Iron Stores are Equally Strong Diagnostic Predictors of a Hemoglobin Response to 12 Weeks of Daily Iron Supplementation in Cambodian Women
Open Access
- 12 May 2021
- journal article
- research article
- Published by Elsevier in The Journal of Nutrition
- Vol. 151 (8) , 2255-2263
Abstract
The WHO recommends daily iron supplementation for all women in areas where the population-level anemia prevalence is ≥40%, despite the fact that hemoglobin (Hb) concentration is generally considered to be a poor prognostic indicator of iron status. In this secondary analysis, we investigated the predictive power of ten baseline hematological biomarkers towards a 12-week Hb response to iron supplementation. Data were obtained from a randomized controlled trial of daily iron supplementation in 407 nonpregnant Cambodian women (18–45 years) who received 60 mg elemental iron as ferrous sulfate for 12 weeks. Ten baseline biomarkers were included: Hb, measured with both a hematology analyzer and a HemoCue; inflammation-adjusted ferritin; soluble transferrin receptor; reticulocyte Hb; hepcidin; mean corpuscular volume; inflammation-adjusted total body iron stores (TBIS); total iron binding capacity; and transferrin saturation. Receiver operating characteristic (ROC) curves from fitted logistic regression models were used to make discrimination comparisons and variable selection methods were used to construct a multibiomarker prognostic model. Only 25% (n = 95/383) of women who completed the trial experienced a 12-week Hb response ≥10 g/L. The strongest univariate predictors of a Hb response were Hb as measured with a hematology analyzer, inflammation-adjusted ferritin, hepcidin, and inflammation-adjusted TBIS (AUCROC = 0.81, 0.83, 0.82, and 0.82, respectively), and the optimal cutoffs to identify women who were likely to experience a Hb response were 117 g/L, 17.3 μg/L, 1.98 nmol/L, and 1.95 mg/kg, respectively. Hb as measured with a hematology analyzer, inflammation-adjusted ferritin, and hepcidin had the best combined predictive ability (AUCROC=0.86). Hb measured with the HemoCue had poor discrimination ability (AUCROC = 0.65). Baseline Hb as measured with a hematology analyzer was as strong a predictor of Hb response to iron supplementation as inflammation-adjusted ferritin, hepcidin, and inflammation-adjusted TBIS. This is positive given that the WHO currently uses the population-level anemia prevalence to guide recommendations for untargeted iron supplementation.Keywords
Funding Information
- Micronutrient Initiative, Sight and Life Foundation
- Canadian Institutes of Health Research
- Michael Smith Health Research BC
This publication has 39 references indexed in Scilit:
- Anemia of Chronic DiseaseSeminars in Hematology, 2013
- Genetic Hemoglobin Disorders, Infection, and Deficiencies of Iron and Vitamin A Determine Anemia in Young Cambodian ChildrenThe Journal of Nutrition, 2012
- Serum hepcidin as a diagnostic test of iron deficiency in premenopausal female blood donorsHaematologica, 2011
- Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesisNature Communications, 2010
- Receiver Operating Characteristic Curve in Diagnostic Test AssessmentJournal of Thoracic Oncology, 2010
- Leukocyte DNA damage in children with iron deficiency anemia: effect of iron supplementationEuropean Journal of Pediatrics, 2010
- Baseline Iron Indices as Predictors of Hemoglobin Improvement in Anemic Vietnamese Women Receiving Weekly Iron-Folic Acid Supplementation and DewormingThe American Journal of Tropical Medicine and Hygiene, 2009
- On risks and benefits of iron supplementation recommendations for iron intake revisitedJournal of Trace Elements in Medicine and Biology, 2007
- Monitoring of hematological, inflammatory and oxidative reactions to acute oral iron exposure in human volunteers: Preliminary screening for selection of potentially-responsive biomarkersToxicology, 2005
- IRON DEFICIENCY IN WOMEN OF FERTILE AGE IN A SWEDISH COMMUNITYActa Medica Scandinavica, 1969