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

• Published in: The Journal of nutrition Vol. 151; no. 8; pp. 2255 - 2263
• Main Authors: Pei, Lulu X, Kroeun, Hou, Vercauteren, Suzanne M, Barr, Susan I, Green, Tim J, Albert, Arianne Y, Karakochuk, Crystal D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2021; American Institute of Nutrition; Oxford University Press
• Subjects: Anemia; Anemia, Iron-Deficiency; Asian People; Biomarkers; Cambodia; Clinical trials; Community and International Nutrition; Dietary Supplements; Female; Ferritin; Ferritins; Ferrous sulfate; Hematology; HemoCue; Hemoglobin; Hemoglobins - metabolism; Hepcidin; Hepcidins; Humans; Inflammation; Iron; Iron sulfates; Medical diagnosis; Nutrition; predictor; Randomized Controlled Trials as Topic; Regression analysis; Regression models; Reticulocytes; Secondary analysis; Studies; supplementation; Supplements; total body iron stores; Transferrin; Transferrins; Women; Womens health; CRP; MCV; ferritin; hepcidin; Cambodia; ROC; total body iron stores; supplementation; AGP; hemoglobin; AUCROC; TIBC; UIBC; VIF; sTfR; HemoCue; iron; predictor; Hb; AIC; women; TBIS
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/nxab108

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.