Assessing the discriminatory ability of hemoglobin concentration to predict iron stores in Cambodian women: A systematic review and individual participant data meta-analysis

Hemoglobin concentration is commonly used as a screening tool to guide iron interventions, as it can be measured more quickly and easily using point-of-care devices than other, more direct measures of iron status (e.g., ferritin). However, anemia is not always caused by iron deficiency. Therefore, we aimed to assess the discriminatory ability of hemoglobin concentration to predict iron stores in Cambodian women of reproductive age, a population where iron deficiency prevalence is low and genetic hemoglobinopathies are common. We conducted a systematic review and individual participant data (IPD) meta-analysis that included 26 studies reporting on 11 databases (including n =3,497 women with available and eligible IPD that included hemoglobin, ferritin, and at least one inflammation biomarker measured in the same individual at the same timepoint). Receiver operating characteristic (ROC) curve analyses were conducted to measure the area under the curve (AUC) and the 95% confidence interval (CI), representing the discriminatory ability of hemoglobin concentration to distinguish between individuals with or without iron deficiency (inflammation-adjusted ferritin <15 μg/L for non-pregnant women; unadjusted ferritin <30 μg/L for pregnant women). Random-effects models were used to estimate pooled effect sizes and 95% CIs. The pooled AUC value [95% CI] for non-pregnant women (9 studies; n =3,377) displayed ‘fair’ discriminatory ability (0.77 [0.74, 0.79]) with high certainty evidence; and for pregnant women (2 studies; n =120) displayed ‘poor’ discriminatory ability (0.57 [0.47, 0.68]) with low certainty evidence. We conclude that hemoglobin is a ‘fair’ predictor of iron status in non-pregnant Cambodian women; thus, it should be used with caution in guiding interventions such as blanket iron supplementation programs. More research is needed to understand if hemoglobin is an acceptable screening biomarker in pregnancy to guide interventions or justify higher doses of supplemental iron during pregnancy. The protocol was registered in PROSPERO (CRD42024578023). Statement of significance Global guidelines currently propose to use hemoglobin screening to guide iron interventions, even though the etiology of anemia is multi-causal, with iron deficiency being only one, albeit important, factor. In this IPD meta-analysis of 26 studies (reflecting 11 datasets with n =3,497 women), we found hemoglobin to be only a ‘fair’ predictor of iron status in non-pregnant women of reproductive age in Cambodia, and thus it should be used with caution in guiding iron interventions, such as blanket iron supplementation programs. More research is needed to understand if hemoglobin is an acceptable screening biomarker in pregnancy to guide interventions or justify the need for additional supplemental iron during pregnancy.