DESCRIPTION

A reduction in hemoglobin production due to an insufficient supply of iron that results in a microcytic, hypochromic anemia

EPIDEMIOLOGY

• Iron deficiency (ID) is the most common nutritional deficiency of children.
• Leading cause of anemia among infants and children in the United States
• Most commonly seen in children ages 12 months to 3 years and in adolescent girls
• Prevalence is variable depending on socioeconomic status, availability of iron-fortified formulas, and prevalence and duration of breastfeeding.
• Prevalence of ID anemia (IDA) in the United States is generally between 1% and 5% of children.

ETIOLOGY

• Causes of inadequate iron supply include dietary deficiency and malabsorption.
  • Dietary deficiency in infants and young children results from introduction of cow’s milk prior to age 12 months, exclusive breastfeeding beyond age 6 months without iron supplementation, and excessive cow’s milk intake (>24 oz/24 h).
  • Malabsorption results from surgical resection of intestine or celiac disease.
  • Certain foods impair iron absorption (tannins in tea and coffee, phytates).
  • Limited consumption of iron-rich foods
• Causes of increased demand include rapid growth and blood loss.
  • Periods of rapid growth include infancy (especially low-birth-weight and premature infants) and adolescence.
  • GI blood loss is most common and includes cow’s milk enteropathy (seen in infants), inflammatory bowel disease (IBD), and bleeding from Meckel diverticulum.
• Other etiologies of blood loss include perinatal loss, menorrhagia, pulmonary hemosiderosis, and hematuria.
• Several studies have shown an association of obesity and iron-restricted erythropoiesis; exact pathophysiologic mechanism for this association is unknown.
• Features of IDA and anemia of inflammation may co-occur.

RISK FACTORS

• A lower iron endowment at birth from prematurity, maternal IDA, or perinatal hemorrhage can result in IDA in infancy.
• Low socioeconomic status
• Decreased absorption of iron in malabsorptive diseases
• Increased losses in disorders associated with GI bleeding or increased menstrual blood loss
• Certain ethnic groups such as African Americans and Hispanics have higher rates of ID. Also, certain ethnic groups (e.g., Southeast Asian) may be at increased risk due to dietary practices. These groups also have a higher incidence of hemoglobinopathies, which can complicate the clinical picture.
• Dietary factors can lead to a decreased intake of iron; for instance, in infants, a lack of iron supplementation for exclusively breastfed infants after 4 months of age, introduction of unfortified cow’s milk before 12 months of age, delayed intake of iron-rich food; in toddlers, excessive cow’s milk consumption; and in adolescents, a poor intake of iron-rich food.

GENERAL PREVENTION

• The American Academy of Pediatrics (AAP) recommends universal screening for IDA and risk factors for ID between the ages of 9 and 12 months. If hemoglobin is <11 g/dL or risk factors for ID are identified, further testing to establish the diagnosis of ID is indicated. Additional screening for patients at risk between the ages of 12 to 15 months and 2 to 5 years is recommended.
• Centers for Disease Control and Prevention (CDC) recommends laboratory screening of all menstruating persons every 5 years and more frequently if risk factors are identified.
• Enteral iron supplementation
  • 1 mg/kg/24 h for infants who are exclusively breastfed beyond 4 months
  • 2 mg/kg/24 h by 1 month of life for low-birth-weight and premature infants who are breastfed because of poor iron stores and increased growth rate
  • Iron-fortified formula for the first 12 months of life for infants who are not breastfed; no additional supplementation needed
  • Encourage iron-enriched cereal when infants are started on solid food.
• Screen hemoglobin level at periodic intervals.

PATHOPHYSIOLOGY

• Iron is required for oxygen transport by hemoglobin.
• IDA and ID without anemia during infancy and childhood can have long-lasting detrimental effects on neurodevelopment.
• Iron absorption and distribution is regulated by hepcidin, a peptide hormone secreted primarily by the liver.
• Iron is absorbed primarily in the duodenum.
• ID develops because of an inadequate supply or increased demand for iron or a combination of these.
• Sequential stages of ID:
  • Depletion of iron stores: reflected by low serum ferritin and low bone marrow stores
  • Iron-deficient erythropoiesis: abnormal hemoglobin synthesis with wide distribution in red blood cell (RBC) size and mild anemia
  • IDA: Microcytosis is evident.