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• > 24 months of age, the growth rate of children slows and the diet becomes more diversified • > 36 months of age, dietary iron and iron status are usually adequate... In iron deficienc

IRON-DEFCIENCY

ANEMIA

• Iron deficiency: ID, a state in which

there is insufficient iron to maintain normal physiologic functions

• Anemia: A hemoglobin concentration

2 SDs below the mean Hb

concentration for a population of the same gender and age range

• Iron-deficiency anemia: IDA, top

cause of anemia

Children are at risk of IDA:

• < 24 months of age: rapid growth + frequently inadequate intake of dietary iron places children at the highest risk of any age group for ID

• > 24 months of age, the growth rate of children slows and the diet becomes more diversified

• > 36 months of age, dietary iron and iron status are usually adequate.

MODIFICATIONS OF IRON

HOMEOSTASIS IN ID

• Tightly regulated by hepcidin-based homeostatic controls

• Hepcidin:

• a peptide hormone, synthesized primarily in the liver

• increases in response to high circulating and tissue levels of iron

• [hepcidin] have a strong direct correlation with [serum ferritin]

• inhibited by (1)

• erythropoiesis

• iron deficiency

• tissue hypoxia

In iron deficiency,

• The transcription of hepcidin is suppressed, facilitates:

• the absorption of iron

• the release of iron from body stores

IRON REQUIREMENTS

• IRON REQUIREMENTS FOR TODDLERS

• 7 mg/day

• IRON REQUIREMENTS FOR TERM INFANTS

• Term infants 0 – 6 months: 0.27 mg/day

• Term infants 7 – 12 months: 11 mg/day

• IRON REQUIREMENTS FOR PRETERM INFANTS

• estimated to be 2 - 4 mg/kg per day PO

• 80% of the iron present in a newborn term infant is accreted during the third trimester of pregnancy.

• The deficit of total body iron in preterm infants

• increases with decreasing gestational age

• worsened by the rapid postnatal growth

• Tranfusions:

• sick preterm infants who receive multiple transfusions are

at risk of iron overload

• Recombinant human erythropoietin:

• further deplete iron stores if additional supplemental iron

is not provided

• Most iron in neonates is in circulating hemoglobin

• As the relatively high hemoglobin concentration of the newborn infant falls during the first 2-3 mo of life,

considerable iron is recycled

• These iron stores are usually sufcient for blood

formation in the first 6-9 mo of life in term infants

• In term infants, anemia caused solely by inadequate

dietary iron usually occurs at 9-24 mo of age and is

relatively uncommon thereafer

• Chronic blood loss

• Commonly causes ID

• Particularly menstrual and gastrointestinal tract bleeding

• Idiopathic pulmonary hemosiderosis: rare

• Involved infants characteristically develop anemia

• more severe

• occurs earlier

than would be expected simply from an inadequate intake

• Occult gastrointestinal tract bleeding may be caused by

• A lesion of the gastrointestinal (GI) tract: peptic ulcer,

Meckel diverticulum, polyp, hemangioma, or

inflammatory bowel disease

• Allergy to cow’s milk

• Infections: Necator americanus, Trichuris trichiura,

Plasmodium, H pylori

• Pallor is the most important clinical sign of iron

deficiency but is not usually visible until the

hemoglobin falls to 7-8 g/dL

• Pallor, tachycardia, and systolic murmur are more prevalent as the microcytic, hypochromic anemia worsens

• Epithelial changes such as atrophy of the papillae of

the tongue and spooning of the fingernails: unusual in children

• Iron defciency has nonhematologic systemic effects

• affect growth

• cause potentially irreversible mental and psychomotor developmental abnormalities in children < 2 years old

DETERMINATION OF IRON STATUS

• Tissue iron stores are depleted

• This depletion is reflected by reduced serum ferritin (<10 – 15 ng/mL), an iron-storage protein, which

provides an estimate of body iron stores in the

absence of inflammatory disease

• Serum ferritin level is the most sensitive and specific test used for the identification of iron deficiency.

• 1 µ/L of SF corresponds to 8 - 10 mg of available storage iron

• Serum iron levels decrease

• The iron-binding capacity of the serum (serum transferrin) increases

• Transferrin saturation falls below normal

• Hemoglobin synthesis is impaired

• Iron defciency progresses to iron-defciency anemia

• With less available hemoglobin in each cell, the red cells become smaller and varied in size

• The red blood cell count also decreases

Complete history:

• Iron sources in the diet: excessive intake (> 700mL per day)

of cow’s milk or low-iron formula

• Menstruation, blood loss

• Medication exposure: hemolysis in G6PD defciency

• Growth and development

• Hyperbilirubinemia, family history of anemia, splenectomy(1)

• Fatigue, decreased exercise tolerance

• Glossitis, koilonychia, angular chelitis

• Signs of systemic illness

Initial laboratory tests:

• Complete blood cell count(1)

• Red blood cell indices (MCH, MCH, RDW)

• Reticulocyte count

• Stool for occult blood

• Urinalysis, serum bilirubin

DIAGNOSIS

DIFERENTIAL DIAGNOSIS

• Diagnosis other than iron deficiency

• Thalassemias

• Hemoglobins C and E disorders

• Anemia of chronic disease

• Lead poisoning

• Sickle thalassemias

• Hemoglobin SC disease

• Iron refractory iron defciency anemia (IRIDA)

• Rare microcytic anemias

• Iron defciency is best prevented to avoid both its

systemic manifestations and the anemia

• Recommended dietary allowance (RDA) for iron:

• The average daily dietary intake

that is sufficient to meet the nutrient requirements

of nearly all individuals (97%–98%)

of a given age and gender.

• Term, breastfed infants

• exclusive breastfeeding for 4 – 6 months (2)

• iron supplementation of 1 mg/kg per day

• starting at 4 months of age (3)

• continued until appropriate iron-containing complementary foods have been introduced

• Preterm infants (<37 weeks), breastfed

• should receive iron supplement of 2 mg/kg per day

• 1 – 12 months

• provided as medicinal iron or in iron-fortified

complementary foods (4)

• Toddlers (1–3 years of age)

• The iron requirements of toddlers would be met and

ID/IDA would be prevented with naturally iron-rich foods

SCREENING FOR ID AND IDA

• Universal screening for anemia: Hb concentration at 1 year old (AAP)

• Risk factors associated with ID/IDA:

• history of prematurity or low birth weight

TREATMENT

• Oral Iron Therapy:

• Convenient,

• Inexpensive,

• Effective means of treating stable patients

• A daily total dose of 3-6 mg/kg of elemental iron in 3 divided doses is adequate, with the higher dose used

in more severe cases

• Maximum dose: 150-200 mg of elemental iron daily

• The low hepcidin levels in patients with IDA ensure

effective iron absorption and the rapid recovery of

hemoglobin levels

• 3 to 6 months of treatment are required for the repletion

of iron stores and the normalization of serum ferritin

levels.

• Long-term use of oral iron is limited by side effects:

• nausea, vomiting, constipation, and metallic taste

• Iron sulfate is the most frequently

used

• Ferrous sulfate is 20% elemental

iron by weight and is ideally given

between meals with juice,

although this timing is usually not

critical with a therapeutic dose

Ferlin 6mg/mL 60mL

• In addition to iron therapy, dietary counseling is

usually necessary

• Excessive intake of milk, particularly cow’s milk, should be limited.

IRON REFRACTORY IRON

DEFCIENCY ANEMIA

• Iron-deficiency anemia is usually acquired

• iron-refractory iron-deficiency anemia (IRIDA): rare

autosomal recessive disorder

• IDA is defined as “refractory” when

• absence of hematologic response (an increase of < 1 g/dL of hemoglobin)

• after 4 to 6 weeks of treatment with oral iron

• IRIDA caused by a mutation in TMPRSS6 gene

• Constitutively high production of hepcidin

=> Blocks the intestinal absorption of iron

• Typical findings include

• a striking microcytosis

• extremely low transferrin saturation

• normal or borderline-low ferritin levels

• high hepcidin levels

• The diagnosis ultimately requires sequencing of

TMPRSS6.

• IRIDA represents less than 1% of the cases of deficiency anemia seen in medical practice(1)

iron-• Poor compliance (true intolerance of Fe is uncommon

• Incorrect dose or medication

• Malabsorption of administered iron

• Ongoing blood loss, including gastrointestinal,

menstrual

• Concurrent infection or inflammatory disorder

inhibiting theresponse to iron

• Concurrent vitamin B12 or folate deficiency

• In most cases, iron resistance is due to disorders of the gastrointestinal tract.

• Partial or total gastrectomy or any surgical procedure that bypasses the duodenum can cause resistance to oral iron

• Hp infection