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Iron deficiency (ID) affects 9%–16% of US women with well-documented morbidity in academic performance, mood, and concentration. Current ID screening depends on the detection of low hemoglobin (ie, anemia, <12.0 g/dL). However, anemia is a late-stage indicator of ID. The study hypothesis was that using higher hemoglobin thresholds would optimize ID screening. The objective was to assess the sensitivity and specificity of hemoglobin to detect ID among nonpregnant, reproductive-age women of 12–49 years and to determine if psychometric characteristics varied by age and race. This cross-sectional study used National Health and Nutrition Examination Survey 2003–2010 data. ID was defined as body iron, calculated using ferritin and transferrin receptors. Logistic regression and receiver operating characteristic (ROC) curves were used to model the predictive probability of ID by hemoglobin values. ID prevalence by body iron was 11.5% (n = 6602). Using <12.0 g/dL, hemoglobin had a sensitivity of 42.9% (95% confidence interval [CI] = 39.4%, 46.4%) and specificity of 95.5% (95% CI = 95.0%, 96.0%) for ID. The ROC curve was optimized at the hemoglobin threshold of <12.8 g/dL with the sensitivity and specificity of 71.3% (95% CI = 68.0%, 74.5%) and 79.3% (95% CI = 78.2%, 80.3%), respectively. The probability of ID at this threshold was 13.5% (95% CI = 11.3%, 15.9%). Hemoglobin better predicted ID among older (22–49 years) vs younger (12–21 years) women (c-index 0.87 vs 0.77,P< 0.001). Among nonpregnant, reproductive-age women, current hemoglobin thresholds are insufficient to exclude ID. A threshold of <12.8 g/dL improves the detection of ID.