Why is aspirin (acetylsalicylic acid) typically not given to children due to the risk of Reye's syndrome?

From the Guidelines

Aspirin is typically not given to younger people, especially those under 21 years of age, due to the increased risk of Reye's syndrome, a rare but potentially fatal condition that causes swelling in the liver and brain. This risk is particularly significant when aspirin is used during viral illnesses like chickenpox or flu 1. For fever or pain in people under 19 years old, healthcare providers recommend alternatives such as acetaminophen (Tylenol) or ibuprofen (Advil, Motrin) instead. The link between aspirin and Reye's syndrome was discovered in the 1980s, after which warnings were added to aspirin products and pediatric use declined dramatically. Some key points to consider when deciding whether to give aspirin to younger people include:

• The risk of Reye's syndrome is increased in children and teenagers who take aspirin during viral illnesses 1
• Aspirin therapy is not recommended in people under 30 years of age, due to lack of evidence of benefit, and is contraindicated in patients under the age of 21 years because of the associated risk of Reye’s syndrome 1
• The exact mechanism of Reye's syndrome is not fully understood, but aspirin appears to interact with viral infections in developing bodies to trigger this dangerous reaction 1
• Even low doses of aspirin can be risky, so parents should check medication labels for acetylsalicylic acid (ASA), the chemical name for aspirin, and avoid giving these products to children and teens unless specifically directed by a doctor for certain medical conditions like Kawasaki disease 1. In general, the use of aspirin in younger people should be approached with caution, and alternative treatments should be considered whenever possible. Aspirin therapy may be considered for primary prevention in patients over 40 years of age with diabetes and one or more other cardiovascular risk factors, but this should be done under the guidance of a healthcare provider 1.

From the FDA Drug Label

Children and teenagers who have or are recovering from chicken pox or flu-like symptoms should not use this product, if changes in behavior with nausea and vomiting occur, consult a doctor because these symptoms could be an early sign of Reyes syndrome, a rare but serious illness Aspirin is typically not given to younger people because of the risk of Reye's syndrome, a rare but serious illness that can occur in children and teenagers who use aspirin while having or recovering from chicken pox or flu-like symptoms 2.

From the Research

Aspirin Use in Younger People

• Aspirin is typically not given to younger people due to the risk of Reye's Syndrome, a rare but severe and often fatal disease 3, 4.
• Reye's Syndrome is characterized by a generalized disturbance in mitochondrial metabolism, eventually resulting in metabolic failure in the liver and other tissues 5.
• The etiology of 'classical' Reye syndrome is unknown, but it is believed to result from an unusual response to a preceding viral infection, which can be modified by exogenous agents such as aspirin 5.

Risk of Reye's Syndrome

• The risk of Reye's Syndrome is higher in children under the age of 12 years, and the use of aspirin in this age group is not recommended 3, 4.
• The incidence of Reye's Syndrome has declined dramatically in the United States since the decline in the use of aspirin among children 4.
• A dose-response relation between the risk of Reye's Syndrome and the dose of aspirin ingested during the antecedent illness provides further supportive evidence for a causal link between Reye's Syndrome and aspirin 4.

Alternative Explanations

• Some studies suggest that the link between aspirin and Reye's Syndrome may not be causal, but rather an association 5.
• However, the majority of the evidence suggests that there is a close link between the devastating encephalopathy Reye's Syndrome and ingestion of aspirin during the febrile prodrome 6.
• Recent in vitro findings have pinpointed the site of action of the drug on the long chain hydroxyacyl-CoA dehydrogenase enzyme, and even at therapeutic concentrations, oxidation is impaired in cultured fibroblasts from patients who have recovered from the disorder 6.