Melatonin Supplementation in Undetermined Pediatric Deaths

Since 2015, the North Carolina Office of the Chief Medical Examiner has investigated seven deaths of infants and toddlers, aged 2 months to 3 years, with exogenous melatonin detected upon toxicological analysis. Melatonin concentrations ranged from 3 to 1,400 ng/mL in postmortem whole blood. While the cause and the manner of all seven deaths were classified as undetermined, the analytical findings are noteworthy. Melatonin is generally considered a safe, natural product appearing in many over-the-counter supplements geared toward young children to facilitate calmness and improve sleep. Melatonin is a neurohormone, which regulates not only circadian rhythms and natural sleep but also other physiological functions. Endogenous melatonin production, derived from essential amino acid metabolism, does not begin until pineal gland maturation at ∼3 months of age with concentrations in plasma peaking during periods of darkness at ∼0.2 ng/mL. Administering commercially available melatonin supplements to infants results in levels substantially greater than endogenous sources, which should not be assumed to be safe just because of their endogenous nature. The finding of exogenous concentrations in some postmortem pediatric cases warrants attention. Several topics of interest surrounding these postmortem melatonin findings will be considered, such as minimal regulatory control over commercial products as well as the potential impact on hazardous sleeping conditions. This manuscript will outline the physiological effects of melatonin and detail the case studies from the North Carolina medical examiner system. Forensic toxicology laboratories should consider including melatonin at exogenous concentrations in their testing schemes for appropriate postmortem infant and toddler cases.