Assessment of iron status

The assessment of iron status cannot rely solely on the concentration of Hb or a hematocrit (Hct) value, as there is usually a large overlap in pregnancy between subjects that have iron deficiency and those that do not [18, 19]. The various categories of iron status, adequate, low or depleted iron stores, iron deficient erythropoiesis, and iron deficiency anemia, are all characterized by a range of values of a number of biomarkers that are sensitive to iron storage, iron transport, or tissue iron deficiency (Table 16.2).

Table 16.2

Cutoff Values to Define Iron Status during Pregnancy

Table 16.2

Cutoff Values to Define Iron Status during Pregnancy

Iron replete

Iron depleted

Iron-deficient erythropoiesis

Iron-deficient

Serum ferritin

>30 mcg/l

<30 mcg/l

<15 mcg/l

<15 mcg/l

Soluble TfRa

<2-4 mg/dl

<2-4 mg/dl

4-5 mg/dl

>6 mg/dl

Hemoglobinb

>110 g/l (1st)

>110 g/l (1st)

>110 g/l (1st)

<110 g/l (1st)

>105 g/l (2nd)

>105 g/l (2nd)

>105 g/l (2nd)

<105 g/l (2nd)

>110 g/l (3rd)

>110 g/l (3rd)

>110 g/l (3rd)

<110 g/l (3rd)

Transferrin saturation

>20-25%

>20-25%

<15%

<15%

Serum Fe

>115 mcg/dl

115 mcg/dl

<60 mcg/dl

< 40 mcg/dl

aSoluble transferrin receptor levels depend on the clinical assay method utilized. These values correspond to values developed from the Ramco ELISA kit.

bHb and hematocrit cut-off levels will vary by trimester; these values were derived from the IOM report [1].

aSoluble transferrin receptor levels depend on the clinical assay method utilized. These values correspond to values developed from the Ramco ELISA kit.

bHb and hematocrit cut-off levels will vary by trimester; these values were derived from the IOM report [1].

A ferritin of <30 mcg/l indicates low iron stores, while a level <12-15 mcg/l is used to indicate depleted stores. The soluble form of the transferrin receptor, TfR, is sensitive to inadequate delivery of iron to cells and thus becomes a sensitive biomarker of iron inadequacy once the serum ferritin is <15 mcg/l. TfR is heavily expressed on the surface of developing red cells and is thus quite responsive to iron deficiency erythropoiesis. There is a strong inverse correlation between ferritin and sTfR such that combinations of these two markers can be used to generate composite indicators that are sensitive to changes in iron status across a wide range [19].

One of the important characteristics of the TfR measurement is that this biomarker is not sensitive to infection and inflammation and in contrast to serum ferritin, a strongly reactive acute phase protein. While these indicators have been validated in a number of settings, their utilization in studies in pregnancy has been quite limited with many clinical trials of supplementation relying only on Hb response to intervention [20]. Some have attempted to come up with proxy prediction rules for iron deficiency, based only on the measurement of Hb and red cell distribution width (RDW) [21], but the need to validate all of the measures within a particular clinical environment makes this approach problematic. Zinc protoporphyrin measurements are a useful indicator of iron status, but these are frequently not available as part of the routine clinical laboratory workup. The utility of these biomarkers to diagnose iron status in pregnancy clearly varies with the expected changes in iron status given the high iron requirements in pregnancy. For example, ferritin becomes insensitive as an indicator in many women by the second trimester because iron stores are already low. At this time, the sTfR or the composite indicator, body Fe, would be useful for indicating further changes in iron status before there is evidence of overt anemia [22].

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