Serum ferritin as an indicator of iron status: what do we need to know?

Abstract

Determination of iron status in pregnancy and in young children is essential for both clinical and public health practice. Clinical diagnosis of iron deficiency (ID) through sampling of bone marrow to identify the absence of body iron stores is impractical in most cases. Serum ferritin (SF) concentrations are the most commonly deployed indicator for determining ID, and low SF concentrations reflect a state of iron depletion. However, there is considerable variation in SF cutoffs recommended by different expert groups to diagnose ID. Moreover, the cutoffs used in different clinical laboratories are heterogeneous. There are few studies of diagnostic test accuracy to establish the sensitivity and specificity of SF compared with key gold standards (such as absent bone marrow iron stores, increased intestinal iron absorption, and hemoglobin response to SF) among noninflamed, outpatient populations. The limited data available suggest the commonly recommended SF cutoff of ,15 mg/L is a specific but not sensitive cutoff, although evidence is limited. Data from women during pregnancy or from young children are especially uncommon. Most data are from studies conducted .30 y ago, do not reflect ethnic or geographic diversity, and were performed in an era for which laboratory methods no longer reflect present practice. Future studies to define the appropriate SF cutoffs are urgently needed and would also provide an opportunity to compare this indicator with other established and emerging iron indexes. In addition, future work would benefit from a focus on elucidating cutoffs and indexes relevant to iron adequacy.Am J Clin Nutr 2017;106 (Suppl):1634S-9S.

Integrating themes, evidence gaps, and research needs identified by workshop on iron screening and supplementation in iron-replete pregnant women and young children

“…Thus, longitudinal studies in today's gynecologic population might yield different cutoffs. For SF concentration, the same cutoffs, admittedly variable in range from ,10 to ,15 mg/L, are used for both nonpregnant women of reproductive age and pregnant women (25,26) and, therefore, fail to consider hemodilution with plasma volume expansion. In addition, ranges of "normal" vary among clinical laboratories (26,27).…”

“…For SF concentration, the same cutoffs, admittedly variable in range from ,10 to ,15 mg/L, are used for both nonpregnant women of reproductive age and pregnant women (25,26) and, therefore, fail to consider hemodilution with plasma volume expansion. In addition, ranges of "normal" vary among clinical laboratories (26,27). Total body iron stores (TBI), currently used in NHANES, is the log ratio of SF to soluble transferrin receptor (sTfR) concentrations and is likely independent of plasma volume expansion, although this has not been determined.…”

“…This gap reflects the lack of evaluation of the full spectrum of iron status with any currently used indicator relative to a nonhematologic health outcome (26). Yet, such health outcome-evaluated indicators would allow for meaningful cutoffs with clinical relevance for assessing the full continuum of iron status.…”

“…However, the evidence was limited because of inconsistent findings and small effect sizes within normal ranges for those reporting improved outcomes with maternal iron supplementation. Presentations and discussion at the workshop echoed this lack of evidence linking iron status to health outcomes either in terms of indicators of iron status (26) or studies examining changes in iron status (13,14,21,23,33,34). Both the USPSTF (1) and the discussion at the workshop noted evidence that supplementation or fortification improved hematologic indicators.…”

“…Although pregnant women with IDA give birth to neonates at a higher risk of low iron stores, this is an intermediate, not a health, outcome. This evidence gap is not to say that one can conclude that leaving ID or IDA untreated is supported by the evidence (13,26,33). Rather, it says that the evidence does not demonstrate the benefit, in part because many studies examine only intermediate outcomes and hematologic indicators.…”