Pediatric Iron Toxicity

Updated: Apr 13, 2016
  • Author: Jennifer S Boyle, MD, PharmD; Chief Editor: Timothy E Corden, MD  more...
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Overview

Background

Iron poisoning is a common toxicologic emergency in young children. Contributing factors include the availability of iron tablets and their candylike appearance. Ferrous sulfate tablets (20% elemental iron) are routinely administered to postpartum women, many of whom have toddlers in the family.

The potential severity of iron poisoning is based on the amount of elemental iron ingested. The amount of elemental iron ingested must be calculated based on the number of tablets ingested and the percentage of elemental iron in the salt. [1]

Children may show signs of toxicity with ingestions of 10-20 mg/kg of elemental iron. Serious toxicity is likely with ingestions of more than 60 mg/kg. Iron exerts both local and systemic effects and is corrosive to the gastrointestinal mucosa and can affect the heart, lungs, and liver. Excess free iron is a mitochondrial toxin that leads to derangements in energy metabolism.

Although iron poisoning is a clinical diagnosis, serum iron levels are useful in predicting the clinical course of the patient. In treatment of iron poisoning, consider both bowel decontamination with whole bowel irrigation and chelation using intravenous deferoxamine.

In addition, chronic iron overload may develop in pediatric cancer patients who receive multiple transfusions. At one center, iron overload was diagnosed in 37% of pediatric patients who received 10 or more transfusions. Chelation therapy may be beneficial in these cases. [2]

To prevent iron poisoning, educate parents about the need for childproofing the home and keeping medications out of reach of children. For patient education information, see the First Aid and Injuries Center, as well as Iron Poisoning in Children and Poison Proofing Your Home.

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Pathophysiology

The absorption of iron is normally very tightly controlled by the GI system. However, in overdose, local damage to the GI mucosa allows unregulated absorption, which leads to potentially toxic serum levels.

Much of the pathophysiology of iron poisoning is a result of metabolic acidosis and its effect on multiple organ systems. Toxicity manifests as local and systemic effects. Typically, iron poisoning is described in 5 sequential phases. No consensus has been reached regarding the number of phases and the times assigned to those phases. Patients may not always demonstrate all of the phases.

Phase 1

Phase 1, initial toxicity, predominantly manifests as GI effects. This phase begins during the first 6 hours postingestion and is associated with hemorrhagic vomiting, diarrhea, and abdominal pain. This is predominantly due to direct local corrosive effects of iron on the gastric and intestinal mucosa. Early hypovolemia may result from GI bleeding, diarrhea, and third spacing due to inflammation. This can contribute to tissue hypoperfusion and metabolic acidosis.

Convulsions, shock, and coma may complicate this phase if the circulatory blood volume is sufficiently compromised. In these cases, the patient progresses directly to phase 3, possibly within several hours.

Phase 2

Phase 2 is known as the latent phase and typically occurs 4-12 hours postingestion. It is usually associated with an improvement in symptoms, especially when supportive care is provided during phase 1. During this time, iron is absorbed by various tissues, and systemic acidosis increases. Clinically, the patient may appear to improve, especially to nonmedical personnel, because the vomiting that occurs in phase 1 subsides. However, laboratory analysis demonstrates progressive metabolic acidosis and, potentially, the beginning of other end-organ dysfunction (ie, elevation of transaminase levels).

Phase 3

Phase 3 typically begins within 12-24 hours postingestion, although it may occur within a few hours following a massive ingestion. Following absorption, ferrous iron is converted to ferric iron, and an unbuffered hydrogen ion is liberated. Iron is concentrated intracellularly in mitochondria and disrupts oxidative phosphorylation, resulting in free radical formation and lipid peroxidation. This exacerbates metabolic acidosis and contributes to cell death and tissue injury at the organ level.

Phase 3 consists of marked systemic toxicity caused by this mitochondrial damage and hepatocellular injury. GI fluid losses lead to hypovolemic shock and acidosis. Cardiovascular symptoms include decreased heart rate, decreased myocardial activity, decreased cardiac output, and increased pulmonary vascular resistance. The decrease in cardiac output may be related to a decrease in myocardial contractility exacerbated by the acidosis and hypovolemia. Free radicals from the iron absorption may induce damage and play a role in the impaired cardiac function.

The systemic iron poisoning in phase 3 is associated with a positive anion gap metabolic acidosis. The following explanations for the acidosis have been proposed:

  • Conversion of free plasma iron to ferric hydroxide is accompanied by a rise in hydrogen ion concentration.
  • Free radical damage to mitochondrial membranes prevents normal cellular respiration and electron transport, with the subsequent development of lactic acidosis.
  • Hypovolemia and hypoperfusion contribute to acidosis.
  • Cardiogenic shock contributes to hypoperfusion.

A coagulopathy is observed and may be due to 2 different mechanisms. Free iron may exhibit a direct inhibitory effect on the formation of thrombin and thrombin's effect on fibrinogen in vitro. This may result in a coagulopathy. Later, reduced levels of clotting factors may be secondary to hepatic failure.

Phase 4

Phase 4 may occur 2-3 days postingestion. Iron is absorbed by Kupffer cells and hepatocytes, exceeding the storage capacity of ferritin and causing oxidative damage. Pathologic changes include cloudy swelling, periportal hepatic necrosis, and elevated transaminase levels. This may result in hepatic failure.

Phase 5

Phase 5 occurs 2-6 weeks postingestion and is characterized by late scarring of the GI tract, which causes pyloric obstruction or hepatic cirrhosis. See the image below.

The oxidative potential of iron was first proposed The oxidative potential of iron was first proposed by Fenton in 1894. The importance of reduced oxygen species in biological reactions became apparent with the discovery of superoxide dismutase by McCord and Fridovich in 1969. The potential role of metal ion catalysis was reported the following year. Subsequently, a plethora of evidence has accumulated linking chronic excess body iron to cardiovascular disease, carcinogenesis, aging, stroke, Alzheimer disease, and Parkinson disease. The organ damage that occurs in the hereditary iron overloading disorders is well documented and can be averted and improved by decreasing the excess iron. Acute iron overload likewise produces tissue and organ damage due to the presence of free ionic iron.
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Epidemiology

Frequency

United States

In 2012, the American Association of Poison Control Centers (AAPCC) reported 3778 single exposures to iron and iron salts: 2165 were in children under the age of 6 years, 133 in children 6 to 12 years old, and 285 in patients 13 to 19 years old; there were seven major outcomes but no deaths. In addition, the AAPCC reported 12,910 single exposures to multiple vitamins with iron, 10,429 of them in children younger than 6 years, with one major outcome and no deaths. No deaths from iron poisoning were reported. [3]

Mortality/Morbidity

Most exposures result in minimal toxicity. However, concentrated iron supplement overdoses can result in serious sequelae and death.

Age

Most exposures involve children younger than 6 years who have ingested pediatric multivitamin preparations. Many of the serious acute ingestions follow the pattern of ingestions in general and occur in children younger than 3 years.

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