the Prevention and Management of Iron Deficiency and Iron Deficiency Anemia in Infants, Children and Adolescents

Screening

Clinical screening for symptoms and signs of iron deficiency anemia, in infants and children, done by the primary health care professional/ pediatricians in primary health care setting/ OPC, improves the early detection of IDA and the neurodevelopmental outcome.

Clinical screening for symptoms and signs of iron deficiency anemia, in adolescent females, at yearly school visit, done by the primary health care professional/ pediatrician in primary health care setting/ OPC, improves the early detection of IDA.

Routine dietary history checklist, for iron containing food in infants, children and adolescents, without non-iron related comorbidities, done by the primary health care professional/ pediatrician in primary health care setting/ OPC, helps identify dietetic problems, improve the early detection of ID/IDA and neurodevelopmental outcome.

-        There is no one test considered gold standard for diagnosing iron deficiency or IDA, so official recommendations vary.

-        There is no sufficient evidence to recommend specific screen tests for IDA.

No studies evaluating the benefits or harms of screening programs for asymptomatic children.

-        Laboratory screening of the general population for ID/IDA is not recommended.

Laboratory testing of infants, children, and adolescents at high risk (identified by clinical screening i.e., symptoms and signs) is recommended.

Diagnosis**

Anemia is diagnosed if hemoglobin level is below the cut-off level for age and sex.

Microcytosis is diagnosed if mean corpuscular volume is below -2 SD for age related reference range.

Iron deficiency is considered if serum ferritin level is below 12 ug/L in all age groups in the absence of infection/ inflammation.

Iron deficiency is considered if serum ferritin level is below 30 ug/L in all age groups in the presence of infection/ inflammation.

Treatment

Oral iron therapy:

Dose: 3-6 mg/kg / day for all ages

Forms:  syrup; tablets (each preparation contains different elemental iron dose) (not exceed maximum dose)

Time: 1hour before or 2 hours after meals with Vitamin C at daytime

Monitoring:   after one month by CBC and reticulocytic count, then at 3, 6 months.

If no response after one month: revise dose, compliance, tolerability, type of formula and consider change of formula for another month.

Duration: for 3 months after recovery of hemoglobin.

Tips for Oral iron intake

- Lower and intermittent dose may be as effective and better tolerated.

- To avoid gastric upset, can be taken at night, and increasing dose gradually.

-  Teeth staining can be avoided by brushing teeth and taking with water.

-        If oral iron is ineffective or is not tolerated, consider other causes of anemia, and refer to Hematologist (avoid parenteral iron therapy).

Packed RBCs should be considered after Hematologist opinion.

Nutritional support with iron rich formulas, solid food, and oral iron support 1-2 mg/kg/day elemental iron should be used to treat asymptomatic iron deficiency anemia in infants.

Referral

Referral to hematologist should be considered in cases of severe anemia, history of recurrent bleeding or with failure of increase in the hemoglobin concentration after proper iron dose and proper way of administration

Prevention of ID and IDA

Daily iron supplementation of 10-12.5 mg elemental iron daily (Drops/syrups) for three consecutive months is recommended as a public health intervention in infants and young children aged 6-23 months, living in settings where anemia is highly prevalent****.

Daily iron supplementation of 30 mg elemental iron daily (Drops/syrups/tablets) for three consecutive months is recommended as a public health intervention in preschool children aged 24 to 59 months, living in settings where anemia is highly prevalent****.

Daily iron supplementation of 30-60 mg elemental iron daily (Drops/syrups/tablets) for three consecutive months is recommended as a public health intervention in school aged children aged 5-12 years, living in settings where anemia is highly prevalent*****.

Daily iron supplementation 30–60 mg elemental iron daily (Tablets), for three consecutive months in a year, is recommended as a public health intervention in menstruating adult women and adolescent girls, living in settings where anemia is highly prevalent*****, for the prevention of anemia and iron deficiency.

Dietary prevention

·        Start complementary feeding with iron rich food.

·        Avoid cow milk, goat milk, soy to infants under12 months of age.

·        From 12 months, cow milk should not exceed 500 ml per day.

·        For non-breast-fed infants, iron fortified formula can play a role in prevention and treatment of IDA.

Skin

Pallor

Nails

Koilonychia

Musculoskletal system

Decreased effort capacity

Exercise limitation

Increased absorption of heavy metals

Lead intoxication

Cardiovascular system

Increased cardiac output

Tachycardia

Cardiomegaly
Heart failure

Gastrointestinal system

Loss of appetite

Angular stomatitis

Atrofic glossitis

Dysphagia

Pica

Gluten enteropathy

Plummer-Vinson syndrome

Central nervous system

Irritability-malaise Fainting
Papilledema Pseudotumor cerebri
6th nerve palsy
Restless leg syndrome

Breath holding spell

Sleep disturbance

Attention deficit Learning difficulty Behavioral disorder

Decrease in perception functions

Retardation in motor and mental developmental tests

Immune system disorders
Decreased resistance against infections

T lymphocyte and polymorphonuclear leukocyte dysfunction

3.1 Increased iron demands

·       Prematurity

·       Infancy

·       Adolescence, especially in females Pregnancy

·       Lactation

·       Regular blood donation

·       Competitive athletics

3.2 Diminished iron supply

·       Prolonged breastfeeding without iron supplementation beyond the fourth month of life

·       Consumption of infant formula low in iron

·       Introduction of fresh cow’s milk before the first birthday

·       Daytime bottle use beyond the twelfth month of life

·       Bottle use in bed

·       Preferred consumption of poultry over red meat, vegan and vegetarian diets

3.3 Blood loss

·       Traumatic or operative blood loss

·       Gastrointestinal bleeding: Inflammatory bowel diseases (IBDs), stomach cancer, colon cancer, colonic polyps, non-steroidal anti- inflammatory drugs, chronic Helicobacter pylori infection, hookworm infection, angiodysplasia

·       Gynecological bleeding: Menorrhagia, uterine fibroids, endometrial carcinoma, use of intrauterine devices over contraceptive pills for birth control

·       Urological bleeding: Schistosomiasis, bladder cancer, glomerulonephritis, kidney trauma

·       Pulmonary bleeding: Lung tuberculosis, congenital lung malformations, lung cancer, idiopathic pulmonary hemosiderosis, Goodpasture’s syndrome, etc.

·       Bleeding diathesis (congenital or acquired)

3.4 Malabsorption of iron

·       Celiac disease (gluten sensitive enteropathy)

·       Atrophic gastritis, gastric surgery

·       Decreased gastric acidity (e.g., antacids, H2 blockers, protein-pump inhibitors)

·       Iron Refractory Iron Deficiency Anemia (IRIDA)

Low-income countries

Developed countries

Prolonged breastfeeding without iron supplementation beyond the 4th month of life

Gastrointestinal bleeding of any etiology as per Table 3a

Limited consumption of meat and fish

Genitourinary bleeding of any etiology as per Table 3a

Diets rich on cereal, or legume-based flours, excess dietary fiber

Iron malabsorption of any etiology as per Table 3a

tea

Multiparity

Hookworm infestation

Schistosomiasis

Malaria (contributes to IDA by causing intravascular hemolysis with hemoglobinuria)

Chronic or repeated infections (functional iron deficiency due to chronic inflammation)

LIFESTAGE

GROUP

AI

(mg/day)

UL

(mg/day)

SELECTED

FOOD

SOURCES

ADVERSE

EFFECTS OF

EXCESSIVE

CONSUMPTION

SPECIAL

CONSIDERATIONS

Infants

Heme

sources:

meat,

poultry, fish

Nonheme

sources:

dairy, eggs,

plant-based

foods,

breads,

cereals,

breakfast

foods

GI distress

Persons with decreased gastric acidity may be at increased risk for deficiency.

Cow's milk is a poor source of bioavailable iron and is not recommended for children <1 yr old.

Neurocognitive deficits have been reported in infants with iron deficiency.

RDA for females increases with menarche related to increased losses during menstruation.

Vegans and vegetarians might require iron Supplementation or intake of iron fortified foods.

GI parasites can increase iron losses via GI bleeds.

Iron supplements can interfere with zinc absorption, and vice versa; if supplements are being used, the doses should be staggered.

0-6 mo

0.27

40

7-12 mo

11

40

Children

1-3 yr

7

40

4-8 yr

10

40

Males

9-13 yr

8

40

14-18 yr

11

45

19-21 yr

8

45

Females

9-13 yr

8

40

14-18 yr

15

45

19-21 yr

18

45

Pregnancy

≤18 yr

27

45

19-21 yr

27

45

Lactation

≤18 yr

10

45

19-21 yr

9

45

Elemental Iron, mg

Cereals

Baby food, brown rice cereal, dry, instant, 1 tbsp

1.8

Baby food, oatmeal cereal, dry, 1 tbsp

1.6

Baby food, rice cereal, dry, 1 tbsp 

1.2

Baby food, barley cereal, dry, 1 tbsp

1.1

Table food, heme iron

Clams, canned, drained solids, 3 oz 

23.8

Chicken liver, cooked, simmered, 3 oz 

9.9

Oysters, Eastern canned, 3 oz 

5.7

Beef liver, cooked, braised, 3 oz 

5.6

Shrimp, cooked moist heat, 3 oz 

2.6

Beef, composite of trimmed cuts, lean only, all grades, cooked, 3 oz

2.5

Sardines, Atlantic, canned in oil, drained solids with bone, 3 oz 

2.5

Turkey, all classes, dark meat, roasted, 3 oz 

2.0

Lamb, domestic, composite of trimmed retail cuts, separable lean only, choice, cooked, 3 oz 

1.7

Fish, tuna, light, canned in water, drained solids, 3 oz 

1.3

Chicken, broiler or fryer, dark meat, roasted, 3 oz 

1.1

Turkey, all classes, light meat, roasted, 3 oz 

1.1

Veal, composite of trimmed cuts, lean only, cooked, 3 oz

1.0

Chicken, broiler or fryer, breast, roasted, 3 oz 

0.9

Fish, salmon, pink, cooked, 3 oz 

0.8

Table food, nonheme iron

Oatmeal, instant, fortified, cooked, 1 cup 

14.0

Blackstrap molasses,^a 2 tbsp 

7.4

Tofu, raw, regular, ½ cup 

6.7

Wheat germ, toasted, ½ cup 

5.1

Ready-to-eat cereal, fortified at different levels, 1 cup 

∼4.5 to 18

Soybeans, mature seeds, cooked, boiled, ½ cup 

4.4

Apricots, dehydrated (low-moisture), uncooked, ½ cup 

3.8

Sunflower seeds, dried, ½ cup 

3.7

Lentils, mature seeds, cooked, ½ cup 

3.3

Spinach, cooked, boiled, drained, ½ cup 

3.2

Chickpeas, mature seeds, cooked, ½ cup 

2.4

Prunes, dehydrated (low-moisture), uncooked, ½ cup 

2.3

Lima beans, large, mature seeds, cooked, ½ cup 

2.2

Navy beans, mature seeds, cooked, ½ cup 

2.2

Kidney beans, all types, mature seeds, cooked, ½ cup 

2.0

Molasses, 2 tbsp 

1.9

Pinto beans, mature seeds, cooked, ½ cup 

1.8

Raisins, seedless, packed, ½ cup 

1.6

Prunes, dehydrated (low moisture), stewed, ½ cup 

1.6

Prune juice, canned, 4 fl oz 

1.5

Green peas, cooked, boiled, drain, ½ cup 

1.2

Enriched white rice, long-grain, regular, cooked, ½ cup 

1.0

Whole egg, cooked (fried or poached), 1 large egg 

0.9

Enriched spaghetti, cooked, ½ cup 

0.9

White bread, commercially prepared, 1 slice 

0.9

Whole-wheat bread, commercially prepared, 1 slice 

0.7

Spaghetti or macaroni, whole wheat, cooked, ½ cup 

0.7

Peanut butter, smooth style, 2 tbsp 

0.6

Brown rice, medium-grain, cooked, ½ cup 

0.5

Fruits 

Vegetables 

Citrus fruits (eg, orange, tangerine, grapefruit) 

Green, red, and yellow peppers 

Pineapples 

Broccoli 

Fruit juices enriched with vitamin C 

Tomatoes 

Strawberries 

Cabbages 

Cantaloupe 

Potatoes 

Kiwifruit 

Leafy green vegetables 

Raspberries 

Cauliflower 

Oxalate-rich foods

Beverages: Coffee, tea (especially black tea)

Cereals: Wheat bran

Chocolate

Fruits: Strawberries

Herbs: Rhubarb, oregano, basil, parsley

Vegetables: Beans, beets (roots and leaves),

celery, spinach, kale

Nuts: Peanuts

Oilseeds: Soybeans

Polyphenol-rich foods

Beverages: Coffee, green tea, black tea, red wine, cider
Cereals: Corn, wheat, rice, oat
Cocoa

Apples, blackberries, raspberries, blueberries, black currant, strawberry, kiwi, cherry, plum, pear, apricot, peach, black

Fruits: grape, red grape

Herbs: Rhubarb, peppermint, parsley

Vegetables: Potato, red cabbage, yellow onion, tomato, broccoli, beans, green or white, chicory, artichoke, curly kale, leek, celery, capsicum pepper Nuts: Walnuts

Oilseeds: Soybeans

Spices

Phytate-rich foods

Cereals: Wheat, oats, rice, corn (maize), barley, sorghum, rye, millet, soybean

Nuts: Walnuts, peanuts, nuts

Oilseeds: Soybeans, linseed, sesame seed, sunflower meal

Vegetables: Dried beans, lentils, peas, chickpeas

Calcium-rich foods

Fruits: Figs
Herbs: Rhubarb
Nuts: Almonds
Oilseeds: Soya beans
Vegetables: Broccoli, cabbage, okra, turnip greens, beans, kale

·       Calculation of dosage should always consider elemental iron content of product.

·       To maximize absorption, iron supplements should:

o   Be taken on an empty stomach with full glass of water or fruit juice, if appropriate (e.g., one hour before or two hours after meals).

o   Be taken in the morning or earlier in the day.

o   Be taken with a supplement or dietary source of Vitamin C (e.g., fruit juice, oranges, tomatoes).

o   NOT be taken with Calcium products (e.g.: supplements, certain antacids) or foods (e.g., dairy products such as milk, cheese, yogurt).

o   NOT be taken with high-oxalate foods (e.g., coffee, tea, spinach, kale, broccoli).

·       Oral iron can cause nausea, vomiting, dyspepsia, constipation, diarrhea, metallic taste or dark stools. If your patient is experiencing GI based adverse effects, consider the following:

o   Start at a lower dose (e.g., one tablet once daily) and titrate up slowly (i.e., every four to five days).

o   Switch to liquid form for smaller dose titrations.

o   Switch to another preparation with less elemental iron.

o   Recommend taking iron with small snack or with meals (however food will decrease iron absorption by 40%).

o   Take at bedtime (however, iron absorption is lowest in evening when Hepcidin hormone levels are highest).

o    Could consider polysaccharide iron complex as an option however, it is more expensive and its effectiveness is no better than other iron salts.

Order a CBC and reticulocytes at two to four weeks to see if the patient is responding to replacement regimen. 

Indicators of response to (i.e., targets for) iron therapy include:

·       Reticulocytosis in four days

·       Increasing hemoglobin >1gm/dl in four weeks

Correction of IDA should be observed within two to four months if appropriate iron dosages are administered, and underlying cause of iron deficiency is addressed.