Physiologically based serum ferritin thresholds for iron deficiency among women and children from Africa, Asia, Europe, and central America: a multinational comparative study

Background: Diagnosis of iron deficiency commonly relies on measurement of serum ferritin concentrations. WHO guidelines identify serum ferritin thresholds for iron deficiency among healthy individuals of less than 15 μg/L for women and less than 12 μg/L for children under 5 years, based on expert opinion. We report thresholds for iron deficiency for apparently healthy non-pregnant women and young children based on physiological indicators. Methods: We performed secondary analyses of cross-sectional data from women (aged 15–49 years) and children (aged 6–59 months) from 12 countries in Africa, Asia, Europe, and central America from available surveys (2007–19). Using haemoglobin and soluble transferrin receptor concentrations as individual-level indicators of iron deficiency, we identified country-specific serum ferritin thresholds. We conducted multivariate meta-analysis using individual participant data to assess multinational heterogeneity and intercountry consistency. Findings: Data were collected from July, 2007 to March, 2019. 18 251 individuals (13 864 women and 4387 children) were included in the final analysis. The thresholds of pooled serum ferritin levels corresponding to the starting point of decline in circulating haemoglobin concentrations were 24·8 μg/L (95% CI 24·4–25·2) for women and 22·1 μg/L (20·8–23·4) for children based on the national survey data from 12 countries. The thresholds were consistent among countries (p_{heterogeneity}: women=0·73, children=0·43) but median serum ferritin concentrations and lower 5% reference ranges differed. In all countries, the prevalence of iron deficiency was higher using physiologically based thresholds than that using WHO current guidelines for women (36·0% [95% CI 25·3–46·8] vs 20·1% [11·5–28·7], p<0·0001) and for children (34·2% [24·3–44·1] vs 16·6% [11·2–22·0], p<0·0001). Interpretation: These results provide evidence that the prevalence of iron deficiency as indicated by physiological measures is substantially higher than those based on current WHO guidelines. The consistency of physiologically based serum ferritin thresholds in apparently healthy women and young children offers a potential means to achieve evidence-informed coordination in thresholds for iron deficiency across populations. The use of physiologically based serum ferritin thresholds could help in detecting the clinical and functional outcomes of iron deficiency. Funding: None.