What Are the Potential Side Effects of Iron Therapy?

Patient Presentation
A 15-month-old caucasian male came to clinic for his health supervision visit. He was developing and growing normally and his parents had no concerns. He was taking a mixed diet appropriate for his age with ~20 ounces of whole milk daily. The pertinent physical exam showed a healthy appearing male with growth parameters at the 75% and a normal examination. His screening laboratory evaluation showed a hemoglobin of 10.6 mg/dL.

The new intern wasn’t sure how to manage the diagnosis of anemia and asked about how much iron to prescribe. His medical record review noted a normal neonatal screening test and normal complete blood count at birth done because of a maternal fever. After discussion with her attending physician, they decided that this presumably was iron deficiency anemia, and they would treat with supplemental iron for 1 month and then followup with repeat labs including a reticulocyte count. The attending noted that in general, additional iron in a healthy infant doesn’t cause problems, so he prescribes 3-6 mEq/kg of elemental iron rounding this up to an amount that is easy for the parent to give. He also told the intern that when the patient comes back she would be able to tell if the infant is getting the iron because his teeth will be non-permanently stained from the iron. The patient’s clinical course at one month showed a hemoglobin of 11.8 mg/dL and a reticulocyte count of 6.3%. His complete blood count was otherwise normal. He was to continue on the iron therapy for an additional 2 months.

Discussion
Anemia is a common problem in pediatrics with an estimated 25% of school age children worldwide being anemic. It can cause cognitive and developmental problems along with impaired immunity. It is defined as “a lower than normal value for the related measurements of hemoglobin, hematocrit, and number of red blood cells”, usually 2 standard deviations below the normal for age. Normal hematological values change with age. The most common type of anemia in childhood is iron deficiency commonly caused by inadequate stores (e.g. premature infant), inadequate intake (e.g. poor nutrition) or blood loss (e.g. menses). Anemia screening is recommended at age 9-12 months, and in adolescent males and females during routine health examinations. As iron deficiency is the most common cause, often a trial of therapeutic iron (2-6 mg/kg/day of elemental iron) is started and then a complete blood count is rechecked ~ 1 month later. If iron deficiency is the cause then there should be an increase of 10-20 g/L. If not other causes must be sought.

For a review of iron deficiency anemia and lead poisoning, click here.
For a review of non-correcting causes of anemia, click here.

Learning Point
Iron is an essential trace element needed mainly for heme synthesis, but also oxidative energy production, mitochrondrial respiration and DNA synthesis.

Short term supplemental oral iron ingestion is known to cause nausea, emesis and abdominal pain due to presumed irritation of the gastrointestinal tract. These problems seem to be dose-dependent. Constipation and diarrhea can also be seen in approximately 6% of children but these problems seem to be less dose dependent. Other short term effects also include harmless discoloration of stools (black) and teeth (grey). For a review of differential diagnosis of abnormal tooth coloring click here or for different color stools click here.

Iron overload can occur in patients with underlying disease states especially those that require blood transfusions including β-thalassemia, sickle cell anemia and other congenital anemias and often with cancer treatment. Iron overload can lead to chronic complications including cardiac toxicity with arrhythmias and congestive heart failure, hepatotoxicity with inflammation, fibrosis and cirrhosis, and endocrine problems including delayed puberty, growth failure, diabetes, hypoparathyroidism and hypothyroidism. Cardiac toxicity is the most common cause of death for patients with β-thalassemia. There have been some studies which showed an increased risk of malaria in patients taking iron supplementation. A 2011 Cochrane Collaboration review and the World Health Organization both recommend treating patients for iron deficiency anemia with iron supplementation in malaria-endemic areas.

Questions for Further Discussion
1. What is your general management plan for anemia found on routine screening?
2. When do you order iron studies and which studies do you order?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Anemia and Iron.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Schumann K, Ettle T, Szegner B, Elsenhans B, Solomons NW. On risks and benefits of iron supplementation recommendations for iron intake revisited. J Trace Elem Med Biol. 2007;21(3):147-68.

Kwiatkowski JL. Oral iron chelators. Pediatr Clin North Am. 2008 Apr;55(2):461-82, x.

Okebe JU, Yahav D, Shbita R, Paul M. Oral iron supplements for children in malaria-endemic areas. Cochrane Database Syst Rev. 2011 Oct 5;(10):CD006589.

Low M, Farrell A, Biggs BA, Pasricha SR. Effects of daily iron supplementation in primary-school-aged children: systematic review and meta-analysis of randomized controlled trials. CMAJ. 2013 Nov 19;185(17):E791-802.

World Health Organization Iron supplementation in children in malaria-endemic regions.
Available from the Internet at http://www.who.int/elena/titles/iron_infants_malaria/en/ (rev. 1/22/14, cited 1/31/14).

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.
    16. Learning of students and other health care professionals is facilitated.

  • Systems Based Practice
    23. Differing types of medical practice and delivery systems including methods of controlling health care costs and allocating resources are known.
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.

    Author

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital