title: Forensic Investigation of Methadone Concentrations in Deceased Breastfed Infants.
abstract: There is a paucity of data to aid in assessing whether postmortem methadone findings in breastfed infants are clinically and/or toxicologically significant. Two cases are reported in which methadone was detected in deceased neonates whose mothers were enrolled in methadone maintenance programs and were breastfeeding. In addition to a complete autopsy and toxicological testing for alcohol, prescription medications, and drugs of abuse, pharmacogenetic analysis was performed for variants in genes related to methadone metabolism and response. In both cases, the postmortem methadone concentration measured in neonatal heart blood was higher than the maximum serum methadone concentration reported in living breastfed infants whose mothers were receiving methadone. However, additional analysis of antemortem blood indicated postmortem redistribution of methadone. Pharmacogenetic results were suggestive of a potential predisposition to methadone toxicity based on studies in adults; the significance of these findings in breastfed neonates requires further research. The medical cause of death was unascertained in both cases.
authors.affiliation: Toxicology Section, Centre of Forensic Sciences, Toronto, ON, Canada.
authors.forename: Parvaz
authors.initials: P
authors.lastname: Madadi
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, and Ivey Chair in Molecular Toxicology, Western University, London, ON, Canada.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Kelly
authors.affiliation: Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada.|Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.|Division of Translational Therapeutics, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Ross
authors.affiliation: Ontario Forensic Pathology Service, Ottawa, ON, Canada.
authors.forename: Charis
authors.initials: C
authors.lastname: Kepron
authors.affiliation: Office of the Chief Coroner of Ontario, Toronto, ON, Canada.
authors.forename: James N
authors.initials: JN
authors.lastname: Edwards
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, and Ivey Chair in Molecular Toxicology, Western University, London, ON, Canada.|Division of Clinical Pharmacology and Toxicology, Department of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D001942:Breast Feeding; D002853:Chromatography, Liquid; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D053593:Forensic Toxicology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008691:Methadone / Q000032:analysis*; D008895:Milk, Human / Q000737:chemistry*; D009294:Narcotics / Q000032:analysis*; D058850:Opiate Substitution Treatment; D020641:Polymorphism, Single Nucleotide; D053719:Tandem Mass Spectrometry
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D009294:Narcotics; D065702:Cytochrome P-450 CYP2B6; D008691:Methadone
keywords: ABCB1; CYP2B6; breastmilk; forensic science; infant; methadone; opioids; toxicology