Review: Diethylene Glycol and Ethylene Glycol Contamination in Pediatric Oral Liquid Medication: A Comprehensive Review of Outbreaks, Toxicity, Clinical Features, and Regulatory Failures

Abstract

Recent outbreaks of acute kidney injury (AKI) in pediatric populations have highlighted a critical global health threat linked to the contamination of oral liquid medications with industrial solvents such as diethylene glycol (DEG) and ethylene glycol (EG). These toxic adulterants, often substituted for pharmaceutical-grade excipients like glycerin or propylene glycol, have caused multiple mass poisoning events across low- and middle-income countries, including India, The Gambia, Uzbekistan, Nigeria, and Indonesia. The 2025 Coldrif cough syrup–associated fatalities in India represent the latest in a recurring pattern of manufacturing failures, inadequate regulatory oversight, and supply-chain vulnerabilities. Children are particularly susceptible due to immature metabolic pathways, low body weight, and reduced renal clearance, making even small exposures potentially lethal. Clinical manifestations typically begin with gastrointestinal and neurological symptoms, progressing within 24–72 hours to severe metabolic acidosis, elevated creatinine, oliguria or anuria, and biopsy-proven acute tubular necrosis. Toxicological analyses frequently reveal high concentrations of DEG and its metabolites. Investigations across outbreaks show that contaminated paracetamol syrups, multi-ingredient cough and cold formulations, teething mixtures, sedatives, and expectorants have repeatedly served as the sources of poisoning. Polypharmacy and the widespread over-the-counter availability of pediatric cough syrups further increase risk, despite limited evidence of therapeutic benefit. The recurring nature of these incidents underscores systemic gaps, including poor-quality excipient sourcing, lack of routine DEG/EG screening, weak laboratory infrastructure, and delayed pharmacovigilance responses. Strengthened regulatory enforcement, mandatory excipient testing, improved traceability, and global harmonization of safety standards are essential to prevent further tragedies. Clinicians and caregivers should exercise caution with pediatric liquid medications, especially multi-ingredient OTC products. This review synthesizes historical and recent evidence to provide an integrated understanding of DEG/EG-induced pediatric AKI, the mechanisms of toxicity, clinical features, risk factors, and regulatory challenges. Urgent, coordinated action is required to ensure the safety of pediatric medications worldwide.