Acetaminophen Overdose in an Extremely Low-Birth-Weight Premature Infant: A Case Report and Review of the Literature

Acetaminophen (paracetamol, APAP) overdose is well characterized in pediatric and adult populations; however, reports of toxicity in premature neonates remain exceedingly rare. Existing literature describing acetaminophen overdose in preterm infants is limited to only four published cases. Acetaminophen metabolism in extremely premature neonates differs substantially from that of older children and adults because of developmental immaturity of glucuronidation and cytochrome P450 oxidative pathways, greater reliance on sulfation, and relatively preserved glutathione stores. These developmental differences may alter susceptibility to hepatotoxicity and complicate the interpretation of conventional toxicity thresholds and treatment strategies in this population. This case highlights one of the smallest and youngest reported premature infants, born at 24 + 4 weeks gestation and weighing 640 g at the time of overdose, who survived a 10-fold intravenous (IV) acetaminophen overdose without apparent sequelae following treatment with N-acetylcysteine (NAC). The infant inadvertently received two supratherapeutic intravenous acetaminophen doses because of a medication error involving a non-formulary medication entry within the electronic medical record. Laboratory evaluation demonstrated elevated acetaminophen concentrations and transient coagulation abnormalities without evidence of hepatocellular injury. N-acetylcysteine therapy was initiated with subsequent normalization of coagulation studies and decline of acetaminophen concentrations to undetectable levels. This report expands the limited literature on acetaminophen toxicity in premature neonates and emphasizes the growing importance of understanding neonatal pharmacokinetics as acetaminophen use in neonatal intensive care units increases, particularly for treatment of hemodynamically significant patent ductus arteriosus (PDA). Further investigation is needed to establish population-specific toxicity thresholds and evidence-based management strategies for extremely preterm infants.