Iron

There has been a significant decrease in iron-deficiency anemia in the past 30 years as a direct result of universal screening guidelines as well as iron fortification of formulas and cereals. It is important for pediatricians to monitor their patients’ iron intake because primary prevention is necessary to prevent irreversible mental, motor, and behavioral effects.

The greatest risk factor for the development of iron-deficiency anemia is the early introduction of cow’s milk (before age 1 year) because of its low iron content and poor bioavailability. Nursing mothers should maintain an adequate source of their own dietary or supplemental iron. Breast milk has low iron content, but it is highly bioavailable. After 6 months of age, breastfed infants require iron-rich foods such as egg yolk, leafy green vegetables, proteins, or iron-fortified cereals. After the introduction of cow’s milk at age 1 year it is important to limit intake to no more than 16 to 24 oz/d to prevent iron deficiency.

All infants can be screened for iron-deficiency anemia between 9 and 12 months of age by assessing dietary iron intake and with laboratory data. Although a hemoglobin value determines anemia, a CBC with RBC indices helps to delineate iron-deficiency from other anemias. One may choose to use an empiric treatment of iron-fortified vitamins when mild iron-deficiency anemia is suspected. Determining serum iron levels and total iron binding capacity will support the use of elemental iron treatment.

Iodine

Iodine is an essential component of thyroid hormone that is crucial for growth and development. Iodine is absorbed through the intestines in the form of iodide and is then taken up by the thyroid gland for incorporation into thyroxin (T4) and triiodothyronine (T3). Before the iodization of salt in 1920, iodine deficiency was endemic in the United States, and it is still the most common preventable cause of mental retardation worldwide. A deficiency of iodine is the most common cause of goiter, an enlargement of the thyroid gland, which, if large enough, may produce symptoms such as hoarseness or dysphagia as a result of local compression. Iodine deficiency and subsequent thyroid hormone deficiency can manifest with symptoms of hypothyroidism, such as weight gain, fatigue, and constipation. The most severe consequence of iodine deficiency is congenital hypothyroidism (mental retardation, deaf-mutism, gait abnormalities, and short stature), which can be prevented by adequate iodine intake both during pregnancy and early infancy (Figure 16-1).

Figure 16-1 Congenital hypothyroidism.

Zinc

Zinc, an essential cofactor necessary for growth and development, is often available in adequate levels for full-term infants fed formula or who are breastfed by mothers who themselves have adequate zinc levels. Zinc deficiency is usually caused by intestinal loss from diarrhea or malabsorptive states but can also be caused by renal disease, malignancy, and skin conditions such as acrodermatitis enteropathica. The clinical diagnosis is supported by findings that include growth failure, dermatitis (an erythematous, scaly rash found on the face and perineal region), and impaired wound healing. Laboratory measurements of zinc are often unreliable because of fluctuations seen in various disease states.

Vitamin A

Vitamin A includes retinols, β-carotenes, and carotenoids. Retinols are the most bioactive form and are found in animal proteins. β-carotenes are derived from plants, such as spinach and other leafy greens. More than half of the vitamin A in the body is stored in the liver in a form bound to retinol-binding protein (RBP); the remaining vitamin A can be found in the kidneys, lungs, and adipose tissue and circulating in the blood. Vitamin A deficiency, although uncommon in the United States, may be caused by increased requirements; decreased intake (associated with poverty); or decreased intestinal absorption, including any process that decreases fat absorption such as bowel disease or cholestasis. Clinical findings associated with vitamin A deficiency most often involve the eyes and the skin. Ophthalmologic consequences include retinal pathology leading to blindness, Bitot spots caused by excessive keratin deposition in the superficial conjunctiva, xerophthalmia, and keratomalacia. Dermatologic manifestations include dry skin; pruritus; dry hair; dry, cracked fingernails; and follicular hyperkeratosis. Deficiency is also associated with anemia, impaired osteoclast activity, and immune dysfunction.

Vitamin B

The vitamin B complex includes eight water-soluble vitamins with distinct roles in cellular metabolism. Deficiency often arises from poor nutritional intake because there are minimal stores of vitamin B in the body. Nutritional sources of vitamin B include most animal products such as beef, poultry, fish, and eggs. It is important to note that vitamin B₁₂ is not available through consumption of plants, and this should be considered when caring for patients on vegetarian and vegan diets.

The role of the vitamin B complex is varied but primarily affects the skin and muscle systems. Deficiency of vitamin B₁ (thiamine) causes beriberi, the symptoms of which include weight loss, extremity pain and weakness, emotional disturbances, and cardiac abnormalities (Figure 16-2). Korsakoff’s syndrome, which is characterized by an irreversible psychosis, is a consequence of chronic thiamine deficiency. Lack of vitamin B₂ (riboflavin) is associated with dermatologic findings such as cheilosis, angular cheilitis, glossitis, and seborrheic dermatitis and with congenital abnormalities such as cleft lip and transverse limb deficiency. Vitamin B₃ (niacin) is a key component in required coenzymes in the body, and its deficiency may lead to pellagra, diarrhea, dermatitis, and dementia. The symptoms of vitamin B₅ (pantothenic acid) and vitamin B₆ (pyridoxine) deficiencies include paresthesias, depression, and fatigue, although lack of these vitamins is uncommon. In infants, deficiency of pyridoxine may cause seizures that are refractory to antiepileptic drugs. Deficiency of vitamin B₇ (biotin) is rare and has been linked to growth impairment in infants.

Figure 16-2 Vitamin B (thiamine) deficiency (beriberi).

Vitamin B₉ (folic acid) deficiency in pregnancy may lead to neural tube defects; deficiency in children and adults may lead to a macrocytic anemia. Humans do not produce folic acid and are therefore dependent on dietary sources, such as leafy greens and fortified breads, flours, and cereals. Folate deficiency may occur with chronic diarrhea, congenital malabsorptive states, and drug interactions. Diagnosis of deficiency can be determined by a serum folate level or a peripheral blood smear demonstrating hypersegmented neutrophils and macrocytes. Treatment for folic acid deficiency includes supplementation with 0.5 to 1 mg/d. Vitamin B₁₂ (cobalamin) deficiency, which may be seen with gastrointestinal disorders, may lead to a megaloblastic anemia as well as cognitive difficulties. Deficiency is rare in infants because of large vitamin B₁₂ stores but can be found in some inherited disorders of metabolism as well as in infants breastfed by mothers with vitamin B₁₂ deficiencies. Diagnosis of deficiency is evident by a low vitamin B₁₂ level. Treatment of vitamin B₁₂ deficiency includes administration of doses of 50 to 100 mg via intramuscular injection.

Vitamin C

Vitamin C (ascorbic acid) is not synthesized by humans and therefore must be obtained through the diet in the form of fruits and vegetables. Vitamin C deficiency manifests as scurvy with symptoms such as gingival hemorrhages, petechial rash, and ecchymosis caused by defective collagen synthesis of blood vessel walls. Children with vitamin C deficiency may also present with bony tenderness, pseudoparalysis, and poor wound healing. Diagnosis of vitamin C deficiency can be made clinically by assessing physical signs and symptoms as well as characteristic radiologic findings, such as costochondral beading known as scorbutic rosary (Figure 16-3).

Figure 16-3 Vitamin C deficiency (scurvy).

Vitamin D

Vitamin D plays a major role in bone mineralization by regulating the levels of calcium and phosphorus in the body through absorption in the intestines and reabsorption in the kidney. Whereas vitamin D₂ (ergocalciferol) is provided in the diet, vitamin D₃ (cholecalciferol) is produced in the skin when 7-dehydrocholesterol reacts with ultraviolet B (UVB) light. Foods naturally rich in vitamin D include eggs and fatty fishes, although foods such as milk, cereal, and bread are often fortified with vitamin D. After vitamin D is produced in the skin or consumed in food, it is converted in the liver and kidney to 1,25 dihydroxyvitamin D (1,25(OH)₂D), the physiologically active form of vitamin D known as calcitriol. Vitamin D deficiency may result from a lack of exposure to UVB radiation; inadequate intake; fat malabsorption; liver or kidney disease, which can impair its conversion to active metabolites; and rarely, genetic disorders. Deficiency is most commonly seen in breastfed infants with inadequate vitamin D supplementation. Dark-skinned children are at increased risk of vitamin D deficiency because increased amounts of melanin in the skin reduce the body’s ability to produce endogenous vitamin D in response to sunlight exposure. American Academy of Pediatrics (AAP) guidelines published in 2008 recommend supplementation of 400 IU/day vitamin D for all infants. The AAP also recommends that older children and adolescents who do not obtain 400 IU/d through diet should take a 400-IU vitamin D supplement daily (Figure 16-4).

Figure 16-4 Vitamin D deficiency.

Deficiency results in disorders of bone mineralization, leading to rickets in children and osteomalacia in adults, as well as inadequate serum calcium and phosphorus concentrations. Clinical presentation of rickets may include bone abnormalities such as genu valgus and varus, craniotabes, and costochondral deformities (which produce the classic “rachitic rosary” on chest radiography).