Why are infants and young children at a higher risk of Adverse Drug Reactions (ADRs) due to their physiological characteristics?

Why Infants and Young Children Are at Higher Risk of Adverse Drug Reactions

Infants and young children are at higher risk of adverse drug reactions (ADRs) primarily due to immature renal function, which impairs drug elimination and leads to accumulation of medications and their metabolites. 1, 2

Physiological Vulnerabilities in Pediatric Populations

Immature Organ Function (Primary Risk Factor)

• Renal immaturity is the most critical factor increasing ADR risk in infants and young children, as immature kidney function significantly impairs drug clearance and leads to prolonged drug exposure 1, 2, 3
• Hepatic metabolism is also immature in neonates and infants, affecting the biotransformation of many medications and contributing to unpredictable drug concentrations 1, 4
• The maturation of body systems involved in absorption, metabolism, transportation, and elimination of drugs is incomplete, making children more prone to specific types of ADRs 2

Age-Specific Pharmacokinetic Differences

• Infants (particularly those under 2 years) have fundamentally different pharmacokinetic profiles compared to older children and adults, with reduced drug clearance being a major concern 5, 1
• Pharmacokinetic analysis has demonstrated that children younger than 2 years have reduced clearance of certain drugs (such as cytarabine), necessitating age-adjusted dosing 5
• The volume of distribution differs significantly in infants due to body composition differences, though this is not primarily related to muscle mass as suggested in the incorrect answer choice 2

Weight-Based Dosing: A Necessary but Insufficient Approach

• While doses must indeed be tailored to specific weight or body surface area in children, this dosing strategy alone does not explain the increased ADR risk—rather, it is an attempt to mitigate the risk created by physiological immaturity 5, 1
• Dosage in infants is generally calculated according to body weight (mg/kg) rather than body surface area, but inappropriate extrapolation from adult doses remains a significant problem 5, 4

High-Risk Pediatric Populations

Infants Are Most Vulnerable

• Infants represent the highest-risk age group for ADRs, with 43.3% of pediatric ADR admissions occurring in this population 6
• The rate of hospital admission due to ADRs in pediatric patients is dramatically higher (75.8%) compared to admissions for other causes (11.9%) 6
• Most ADRs in children are serious (75.8%), though the majority (93.4%) resolve without sequelae 6

Contributing Factors Beyond Physiology

• Off-label and unlicensed drug use is extremely common in pediatric populations, particularly in neonatal intensive care units, further increasing ADR risk 1, 4
• Polypharmacy and multiple illnesses in critically ill infants compound the risk 1
• Inappropriate formulations and bedside medication manipulation create additional opportunities for adverse events 1

Common Pitfalls and Misconceptions

The incorrect answer choices reveal important misconceptions:

• Infant boys do NOT have higher muscle mass leading to increased volume of distribution—this is physiologically inaccurate and not a recognized risk factor for ADRs 2
• Children's skin is actually THINNER than adult skin, not thicker, and does not require higher dosages of topical medications—in fact, increased percutaneous absorption in infants can lead to systemic toxicity from topical agents 2
• Weight-based dosing is a mitigation strategy, not the underlying cause of increased ADR risk 5

Clinical Implications

• Approximately 20.8% of pediatric ADRs are preventable or probably preventable, highlighting the importance of careful prescribing practices 6
• Vaccines, antibacterials, and anti-inflammatory medicines are the most frequently implicated agents in pediatric ADRs 6
• Active pharmacovigilance tailored to the pediatric population is essential, as adult ADR data cannot be reliably extrapolated to children 1, 3