Epidemiology

Iron deficiency is the most common nutrient deficiency worldwide and accounts for 50% of the world’s anemia burden. It is the only nutrient deficiency that is found in both industrialized and nonindustrialized countries. There is a bimodal peak of occurrence in pediatrics with increased rates seen in infancy and menstruating adolescent women. It is estimated in the United States that up to 7% of toddlers, 9% of adolescents, and 16% of women of childbearing age is iron deficient.

Pathophysiology

Iron is a ubiquitous metal that is found in most cells within the human body. It is a critical ingredient for effective red cell production but also plays a role in other biochemical pathways including myoglobin formation, energy metabolism, neurotransmitter production, collagen formation, and immune system function. Approximately 1 to 2 mg of iron enters and leaves the body daily. Gastrointestinal (GI) absorption of iron occurs primarily in the proximal duodenum and is a tightly controlled process that is responsive to iron status, erythropoietin demand, hypoxia, and inflammation. The main regulator of iron absorption is hepcidin, which serves as a negative regulator of iron absorption and macrophage iron release.

Within the body, iron is distributed in 3 pools including transport, functional, and storage iron. Absorbed iron is bound to transferrin for transport in the plasma and accounts for only 0.1% of total body iron. Functional iron accounts for 75% of the total body iron and is predominantly used for hemoglobin production (70%) with the remaining in muscle and other tissues. Excess iron is stored in tissues (primarily liver, bone marrow, and spleen) as ferritin. The amount of daily iron absorption is low relative to ongoing demands necessitating iron recycling of senescent red cells by macrophages. Although iron absorption is tightly regulated, there is no mechanism to regulate iron loss.

At birth, infants have high total body iron stores (75 mg/kg of iron). These iron stores support rapid neonatal growth but are only adequate until about 6 months of age. At this point, iron-enriched cereals should be included in the first foods introduced into an infant’s diet. In preterm infants, the total body iron stores are decreased compared with full-term infants although the proportion to body weight is similar. Preterm infants should receive iron supplementation because they undergo more rapid postnatal growth than full-term infants and exhaust their iron stores by 2 to 3 months of age. This high iron requirement will decrease toward the end of the second year of life as the rate of growth decreases. Iron requirements again rise with the rapid growth seen in adolescents, and this is further compounded by adolescent women who have ongoing iron losses through menstruation.

Iron deficiency is always secondary to an underlying source and results from an interplay between increasing iron requirements with growth, inadequate iron intake, excessive iron losses, or poor absorption. Table 1 provides a list of potential causes of iron deficiency. Further discussion is warranted on the most common causes of iron deficiency in pediatric patients, including cow’s milk ingestion in toddlers, menstruating adolescents, and celiac disease (CD).

For many toddlers, the transition from drinking breast milk or formula to solid food can be a challenge. This is further compounded by the continued use of a bottle after the age of 12 months. With the transition to cow’s milk many toddlers drink excessive amounts (>24 ounces per day) preferentially over solid food. Cow’s milk contributes to the development of iron deficiency through multiple mechanisms. It is a poor source of iron and its excessive use displaces iron-rich foods. Components in cow’s milk, casein and calcium, in high amounts directly interfere with iron absorption. Excess cow’s milk can also lead to GI inflammation, which can result in occult GI blood loss.

For menstruating women, dysfunctional uterine bleeding or menorrhagia can result in significant iron loss over time. The definition of menorrhagia is a blood loss of greater than 80 mL in one menstrual cycle. Unfortunately this is not a practical definition and leaves clinicians with little guidance as to how to make this diagnosis. Just asking an adolescent if her period is “heavy” is fraught with pitfalls. A more thorough clinical history is needed. Table 2 provides clinical pearls for diagnosing menorrhagia.

CD is a chronic immune-mediated enteropathy secondary to a sensitivity to gluten proteins. The prevalence of CD is estimated to be 1% in the United States and European countries. The classic symptoms of pediatric CD include failure to thrive, malnutrition, and diarrhea. Recently new clinical patterns of CD presentation in pediatric patients are emerging, thus requiring a higher index of suspicion on the clinician’s part. There has been a shift toward CD being diagnosed at a later age, most do not present with classic symptoms, there is little to mild GI symptoms, associated non-GI symptoms are common, and 10% are overweight. High-risk groups for CD include patients with a first-degree family member with CD, specific genetic disorders (Turner, Williams, and Down syndromes), type 1 diabetes mellitus, other autoimmune disorders, iron deficiency anemia (especially recurrent), and persistently elevated aminotransferase levels. In pediatric patients with iron deficiency it has been reported that 4.4% to 15.5% will have CD.

Clinical Manifestations

The consequences of iron deficiency are systemic and include neurocognitive effects, epithelial changes, and the systemic consequences of anemia. Studies have repeatedly demonstrated that children with iron deficiency have an associated impaired motor and mental functioning. Effects on epithelial cells include angular stomatitis and glossitis. Rarely patients can develop Plummer-Vinson syndrome with the formation of an esophageal web. Long-standing iron deficiency can lead to koilonychias, which is “spooning” of the nails. Some iron-deficient patients may develop pica, which is the compulsion to consume nonfood items like ice, dirt, or clay. The associated signs of anemia depend on the severity of the anemia as previously discussed.

Diagnostic Evaluation

Table 3 describes the common tests of iron. As a person becomes iron deficient, there are progressive changes that occur initially in iron stores and ultimately to the production of RBCs ( Table 4 ). Depending on the time in which laboratory testing is obtained there will be variable laboratory findings. Using a CBC as a screen for iron deficiency only detects the more severe forms as it is a late clinical finding. Although iron deficiency anemia is classically described as a microcytic anemia, there is a brief time when it is a normocytic anemia. The reticulocyte count is low relative to the degree of anemia. Mild to moderate thrombocytosis (range of 500–700,000/mcL) occurs frequently. Table 5 lists common laboratory findings in iron deficiency anemia and how to differentiate from AI and thalassemia trait.

Table 5

Laboratory differences between iron deficiency anemia, AI, and thalassemia trait

Clinical Test	Iron Deficiency Anemia	Anemia of Inflammation	Thalassemia Trait
Serum ferritin	Low	Normal to high	Normal
Serum iron	Low	Low	Normal
TIBC	High	Low	Normal
Transferrin saturation	Low	Low	Normal
MCV	Low	Low to normal	Low
RDW	High	High	Normal

Only gold members can continue reading. Log In or Register to continue

Share this:

• X
• Facebook

Related

Related posts:

1. Acquired Aplastic Anemia in Children
2. Abnormalities of the Erythrocyte Membrane
3. Pediatric Thrombophilia
4. Pediatric Therapeutic Apheresis

Stay updated, free articles. Join our Telegram channel

Join