ID progresses through 3 phases: iron depletion, iron restricted-erythropoiesis, and finally, frank IDA. Severe anemia resulting from long-standing ID may require emergency medical care. However, even mild ID without anemia warrants identification and appropriate treatment given the potential neurocognitive effect. While no single laboratory test can definitively diagnose ID or IDA, many laboratory tests are available and can confirm the diagnosis when assessed in combination and within the context of a child's clinical presentation and history (see Table 18.2). From a full complete blood cell count with indices (CBC), a microcytic anemia demonstrated by a low Hb and mean corpuscular volume (MCV), in combination with an elevated red cell distribution width (RDW), is most consistent with IDA. In the absence of anemia, the reticulocyte hemoglobin equivalent (CHr or Ret-He) obtained with many automated hematology analyzers is the earliest peripheral blood marker to become abnormal in ID by identifying iron-deficient reticulocytes. CHr or Ret-He has shown good sensitivity and specificity for screening children and adults for IDA in systematic reviews.66 Serum ferritin is the most commonly used iron measure to determine overall body iron stores.
Ideally, initial screening should be performed with a full CBC with CHr or Ret-He, if available, and serum ferritin. If an isolated point-of-care Hb is utilized to identify anemia, a full CBC with CHr or Ret-He and/or serum ferritin should then be obtained to confirm the presence of a microcytic anemia and low stores, which confirms the diagnosis of IDA. Serum ferritin is an acute phase reactant and may be elevated in patients with anemia associated with inflammation or in obesity (see Table 18.3). However, in an otherwise well child, the ferritin can be considered reliable, and a low serum ferritin is always consistent with ID. In patients with an acute or chronic inflammation, concomitantly assessing C-reactive protein level may determine whether inflammation is contributing to the anemia. Other specific measures of iron status include: transferrin saturation (calculated value of serum iron over total iron binding capacity), serum or soluble transferrin receptor 1 (sTfR1) concentration, zinc protoporhyrin-to-heme ratio, and plasma hepcidin (see Table 18.3).
The historical recommendations for iron screening in children are a Hb of 11.0 g/dL and serum ferritin of 10 to 12 mcg/L as threshold values.31 However, in children, physiologically based serum ferritin thresholds appear to be higher, 17.9 mcg/L to 20 mcg/L.67,68,69 An Hb level of 11.0 g/dL was associated with extremely low serum ferritin (2.4-4.6 mcg/L) in these children.67,68 A minimum serum ferritin threshold of 15 mcg/L is recommended but higher thresholds may be appropriate. Recent work shows that capillary Hb values measured by point-of-care instrument readings in toddlers were suboptimal (numerically higher) in assessing anemia compared to venous blood collected simultaneously and assayed by standard instrumentation.70 Capillary samples and point-of-care machines are not well studied in older children. Specific newer data about how to screen for ID in older children are limited, but utilizing other measures of erythrocyte iron (zinc protoporphyrin/heme ratio and CHr or Ret-He) may be more effective than Hb and traditional erythrocyte indices in this population.71,72,73,74 However, development of age-based reference intervals for these newer biomarkers is needed.75