Evidence-Based Strategies for Common Clinical Questions

Nothing IRONic About It: Diagnosis & Treatment of Iron Deficiency

Author: Kelly Meyer, MD | Chief Resident – Pediatrics

Column Editor: Kathleen Berg, MD | Co-Director, Office of Evidence-Based Practice | Pediatric Hospitalist, Division of Pediatric Hospital Medicine | Associate Professor of Pediatrics, UMKC School of Medicine 

Iron is an essential mineral needed for many processes in the body. Dietary iron needs are higher in children than adults due to their rapid growth. Throughout the United States, iron deficiency occurs in approximately 7% of children ages 1-5 years, with the highest prevalence of nearly 14% in ages 1-2 years.¹ In nonpregnant adolescents, iron deficiency prevalence is similarly high at nearly 10%.²

There are many factors that place children at risk for iron deficiency. Premature infants are at high risk due to the missed third trimester of pregnancy, when infants accumulate significant iron stores, as well as a higher likelihood of iatrogenic losses.³ In infants who mainly or exclusively breastfeed, iron stores are thought to be depleted by around 4-6 months of age with inadequate levels in breastmilk to meet daily needs. Additionally, infants fed cow’s milk before 12 months of age as well as children ages 1-5 years drinking more than 24 ounces of cow’s milk per day are at higher risk.⁴

Patients with iron deficiency anemia (IDA) often present with nonspecific signs and symptoms, so a low threshold for testing should be maintained. Often, providers associate dizziness, pica, pallor, or tachycardia with anemia. IDA may also present with fatigue, exercise intolerance, impaired immune function and neurocognitive delays^4,5 which may be more easily missed.

In addition to testing when suspicious for iron deficiency, routine screening for anemia is recommended at several ages. For preterm or low birth weight infants not receiving formula fortified with iron, initial screening with hemoglobin/hematocrit should occur at 6 months of age. In term infants, this can be delayed to 9-12 months. Adolescent females should be screened after menarche and then every 5-10 years. This screening should be increased to annually if the teenager has a history of IDA, heavy menstrual bleeding, or poor iron intake.⁴ Children should also be screened more often if there are concerns for food insecurity.

If screening hemoglobin is low, a complete blood count should be obtained. Anemia with low mean corpuscular volume, low mean corpuscular hemoglobin concentration, and high red cell distribution width is suspicious for IDA. While not required for treatment initiation, low ferritin is highly sensitive and specific for iron deficiency.^5,6

Iron supplementation is recommended routinely for premature infants (born at less than 37 weeks gestation) beginning at 2-6 weeks of age at a dose of 2-3 mg/kg/day of elemental iron and should be continued for at least 6-12 months.³ In term infants who mainly breastfeed, iron supplementation is recommended at a dose of 1 mg/kg/day until the infant is taking sufficient iron-containing solid foods.⁷

In children with diagnosed mild to moderate IDA, treatment is recommended with 3-6 mg/kg/day of elemental iron. While iron polysaccharide complex preparations were developed for improved palatability, ferrous sulfate remains the oral iron of choice due to superior efficacy likely due to better gastrointestinal absorption.⁸ Historically, ferrous sulfate dosing has been divided 2-3 times per day in an effort to further improve absorption through repeat administration. However, medication noncompliance is a common barrier to therapy.⁹ Additionally, adult studies suggest that the first morning dose increases serum hepcidin for 24 hours which limits the absorption of subsequent doses that day.¹⁰ Therefore, to improve compliance and absorption, current evidence supports the use of once-daily dosing of ferrous sulfate at 3 mg/kg.^8,10 Administration without food but with a vitamin C-containing drink has been shown to improve absorption.^4,6 Patients and their families should be counseled on common adverse effects including metallic taste, nausea, constipation and dark stools.⁵ Patients with IDA should receive treatment for three months prior to reassessment.^5,11 Those with severe or persistent IDA or additional medical complexity may require packed red blood cell transfusions or parenteral iron for more rapid correction.

Prevention and prompt treatment of IDA is needed to improve short- and long-term neurodevelopmental outcomes. Therefore, assessing needs for iron supplementation or treatment should be at the forefront of care starting in our youngest patients. Patients without identifiable risk factors, with lack of response to oral therapy, or with severe disease may benefit from additional work-up and referral to a pediatric hematologist.

References:

1. Gupta PM, Perrine CG, Mei Z, Scanlon KS. Iron, anemia, and iron deficiency anemia among young children in the United States [published correction appears in Nutrients. 2017 Aug 15;9(8):]. Nutrients. 2016;8(6):330. Published 2016 May 30. doi:10.3390/nu8060330.
2. Gupta PM, Hamner HC, Suchdev PS, Flores-Ayala R, Mei Z. Iron status of toddlers, nonpregnant females, and pregnant females in the United States. Am J Clin Nutr. 2017;106(Suppl 6):1640S-1646S. doi:10.3945/ajcn.117.155978.
3. McCarthy EK, Dempsey EM, Kiely ME. Iron supplementation in preterm and low-birth-weight infants: a systematic review of intervention studies. Nutr Rev. 2019;77(12):865-877. doi:10.1093/nutrit/nuz051.
4. American Academy of Pediatrics. Screening for Anemia. In: McInerny TK, Adam HM, Campbell DE, DeWitt TG, Foy JM, Kamat DM, eds. American Academy of Pediatrics Textbook of Pediatric Care. American Academy of Pediatrics; 2017.
5. Peyrin-Biroulet L, Williet N, Cacoub P. Guidelines on the diagnosis and treatment of iron deficiency across indications: a systematic review. Am J Clin Nutr. 2015;102(6):1585-1594. doi:10.3945/ajcn.114.103366.
6. Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015;372(19):1832-1843. doi:10.1056/NEJMra1401038.
7. Baker RD, Greer FR; Committee on Nutrition American Academy of Pediatrics. Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age). Pediatrics. 2010;126(5):1040-1050. doi:10.1542/peds.2010-2576.
8. Powers JM, Buchanan GR, Adix L, Zhang S, Gao A, McCavit TL. Effect of low-dose ferrous sulfate vs. iron polysaccharide complex on hemoglobin concentration in young children with nutritional iron-deficiency anemia: A randomized clinical trial. JAMA. 2017;317(22):2297-2304. doi:10.1001/jama.2017.6846.
9. Powers JM, Daniel CL, McCavit TL, Buchanan GR. Deficiencies in the management of iron deficiency anemia during childhood. Pediatr Blood Cancer. 2016;63(4):743-745. doi:10.1002/pbc.25861.
10. Powers JM, Buchanan GR. Disorders of iron metabolism: New diagnostic and treatment approaches to iron deficiency. Hematol Oncol Clin North Am. 2019;33(3):393-408. doi:10.1016/j.hoc.2019.01.006.
11. Finkelstein JL, Herman HS, Guetterman HM, Peña‐Rosas JP, Mehta S. Daily iron supplementation for prevention or treatment of iron deficiency anaemia in infants, children, and adolescents. Cochrane Database Syst Rev. 2018;2018(12):CD013227. Published 2018 Dec 17. doi:10.1002/14651858.CD013227.