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Question:

A 6-month-old boy is brought to the clinic for a wellness visit.  The mother states he has been doing well since his last visit and has had no recent illnesses.  The patient was born at term and has no chronic medical conditions.  He takes no medications aside from vitamin D supplementation.  The patient had been exclusively breastfed.  The mother recently began introducing pureed fruits and vegetables.  The patient continues to breastfeed but does not consume iron-fortified cereal.  Vital signs are normal.  The anterior fontanelle is open and flat.  The oropharynx is clear.  The neck is supple, and cardiopulmonary examination is unremarkable.  The abdomen is soft with no organomegaly.  It is explained to the mother that the patient is at risk for developing iron deficiency anemia.  If no dietary changes are made, which of the following laboratory values is most likely to decrease first in this patient?

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Explanation:

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Beginning around age 6 months, term infants are at risk for developing iron deficiency.  They are typically born with enough iron required for the first few months of life.  As iron is lost steadily by shedding epithelium (eg, skin, intestinal tract), it must be replenished through dietary intake; newborns also require additional iron to support rapid body growth.  Breastmilk contains only a low concentration of iron.  Therefore, breastfed infants who do not receive additional iron-rich foods are at risk for developing iron deficiency.

Iron deficiency progresses through the following stages:

  1. Decreased iron storage:  When there is a net negative iron balance, iron is first removed from the storage pool (eg, hepatocytes, reticuloendothelial system); iron is stored intracellularly within ferritin complexes.  Ferritin is also found in the blood, and serum levels generally fluctuate in proportion to iron stores.  Therefore, the body's depletion of storage iron can be detected through a low serum ferritin level.

  2. Iron-limited erythropoiesis:  As iron stores become depleted, serum iron levels decrease, followed by a compensatory rise in transferrin and a resultant decrease in transferrin saturation (Choice E).  During this phase, there is iron-limited erythropoiesis, in which newly made erythrocytes (ie, reticulocytes) are iron deficient and reticulocyte production may begin to be limited.  Because mature erythrocytes have a slow turnover (ie, 120 days), most cells sampled during this stage still have normal morphology, and the total hemoglobin value may still be normal.

  3. Iron deficiency anemia:  If iron deficiency continues, the last phase is frank iron deficiency anemia, which is reflected by a low hemoglobin level with microcytosis (low mean corpuscular volume [MCV]) and hypochromia (low mean corpuscular hemoglobin concentration [MCHC]) in most erythrocytes (Choices B and C).  Reticulocyte production decreases, resulting in an inappropriately low number of reticulocytes (Choice D).

Therefore, a patient in the earliest stages of iron deficiency anemia would likely have only decreased ferritin with an otherwise normal transferrin saturation, MCV, MCHC, and reticulocyte count.

Educational objective:
Infants who do not receive adequate iron supplementation are at risk for developing iron deficiency, which progresses in stages as total body iron is depleted.  The earliest stage involves loss of iron in storage (decreased serum ferritin), followed by iron-limited erythropoiesis with decreased serum iron and transferrin saturation.  Frank iron deficiency anemia, involving the classic findings of low hemoglobin, microcytic/hypochromic erythrocytes, and a low reticulocyte count, is a late finding.