The Toxicology of Methadone‐Related Death in Infants Under 1 Year: Three Case Series and Review of the Literature

Paul, Anthea B. Mahesan; Simms, Lary; Mahesan, Arnold M.

doi:10.1111/1556-4029.13410

Cited by 10 publications

(6 citation statements)

References 30 publications

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“…Lastly, methadone has been associated with a prolonged QT interval, increasing the risk of sudden death [7]. While reports of fatal intoxication in the paediatric population are relatively common [8], to the best of our knowledge, only few cases regarding infants under 1 year have been described in the literature up to this date [2,9].…”

Section: Discussionmentioning

confidence: 99%

“…While reports of fatal intoxication in the paediatric population are relatively common [ 8 ], to the best of our knowledge, only few cases regarding infants under 1 year have been described in the literature up to this date [ 2 , 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…What is more, being therapeutic and toxic level mostly referred to adults, effects are reasonably magnified in the paediatric population. Nevertheless, the determined concentration lies in the range detected in fatal cases in infants under 1 year (ranging from 69 to 700 ng/mL) [ 2 ].…”

Section: Discussionmentioning

confidence: 99%

“…Methadone fatal and non-fatal intoxications were described in infants, often breastfed, in the population under 1 year of age, addressing several pathological, toxicological and pharmacological aspects of acute and chronic methadone intoxication [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

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Infant urinary metabolomic profile in a fatal acute methadone intoxication

et al. 2022

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A case report suspicious for a Sudden Infant Death Syndrome is here described. Pathological findings were consistent with an acute respiratory failure while toxicological analysis revealed an elevated blood methadone concentration. Death was then ascribed to an acute methadone intoxication. In addition to the routinary approach, the urinary sample collected at autopsy was investigated with a 1H NMR metabolomic approach and the identified metabolomic profile was challenged with the urinary metabolomic profiles previously obtained from 10 newborns who experienced perinatal asphyxia and 16 healthy control newborns. Intriguingly, the urinary profile of the methadone intoxicated infant was very similar to those belonging to the perinatal asphyxia newborns, especially to those belonging to the newborns characterised by the worst outcome. The results offer several hints on a shared metabolic derangement between different mechanisms of asphyxia/hypoxia. To the best of the authors’ knowledge, this is the first report of the use of a metabolomic approach in a pathological case, in which metabolomics offers useful additional information regarding the mechanism and the cause of death.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Infant urinary metabolomic profile in a fatal acute methadone intoxication

et al. 2022

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“…Important legal, safety, and medical implications were included for children in homes with prescribed and non-prescribed opioids to recognize the increased risk for accidental ingestion. Unlike survival cases, the data presented in this work identify pathological observations for sudden and unexpected pediatric deaths and specific postmortem toxicological concentrations, which will add to the sparse literature examples of opioid drug poisonings in this population [18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Pediatric opioid fatalities: What can we learn for prevention?

Bishop-Freeman

Young

Aurelius

et al. 2021

Journal of Forensic Sciences

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The aim of this study was to highlight 19 cases investigated by the North Carolina Office of the Chief Medical Examiner over the last 12 years involving accidental or undetermined manner of death opioid ingestions leading to fatalities in young children. These pediatric ingestions have closely mirrored the opioid epidemic in adults transitioning from prescription medications to illicit drugs including fentanyl and fentanyl analogues. Unlike a typical adult ingestion for purposes of self-harm or pleasure, poisonings in toddlers and infants are usually the result of curiosity, exploration, a decreased sense of danger, or imitation of adult or older sibling behavior. Eleven of the decedents were between the ages of 8 and 24 months. Among the cases were 12 prescription opioid exposure deaths and 7 illicit drug poisonings. A majority of the decedents were found unresponsive in an unkept home and/or in unsafe sleeping spaces with easy access to drugs or drug materials, which stresses the importance of safe pediatric sleeping conditions. After a complete pathological investigation, several of the cases had physical or scene evidence demonstrating that foil, plastic, or paper small enough to be ingested can contain enough potent opioid to cause death. Details from the toxicological investigation are included for each case to provide postmortem whole blood drug concentrations for forensic practitioners. Accidental pediatric poisonings are preventable. Risk reduction through improving awareness and education of the dangers of opioids is a key factor in mitigating these tragedies.

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Toxicological and histological analyses for a stillborn delivered by a mother under methadone maintenance therapy

et al. 2018

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Purpose Based on autopsy findings and toxicological results, it was ascertained whether chronic fetal exposure to methadone (MTD) could have caused intrauterine death of a fetus born to a mother under MTD maintenance therapy.Methods Complete fetal autopsy, placental examination and toxicological and histological analyses were performed on a 39-week stillborn fetus, whose mother had regularly taken MTD during the pregnancy. The MTD and its main metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) were quantified in fetal tissues (brain, liver and kidney) by ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). A fully validated toxicological analytical method was developed.Results High levels of MTD and EDDP were present in all samples. The EDDP/MTD ratios were similar in the liver and kidney, but in the brain MTD was predominant. Placental histology showed a thrombotic, partially organised lesion in the first branches of the umbilical vein (chorionic venous vessels) and delayed villous maturation (DVM) was diffusely found in the parenchyma.Conclusions High levels of MTD and EDDP correlate with chronic fetal exposure to MTD maintenance therapy in pregnancy. Placenta DVM can be associated with the MTD exposure, indirectly affecting glycaemic balance. Fetal cause of death seemed to be related to a global hypoxic-ischemic status as a combination of chronic fetal MTD intoxication, placental DVM and impaired placenta blood flow due to chorionic thrombosis.

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The Toxicology of Methadone‐Related Death in Infants Under 1 Year: Three Case Series and Review of the Literature

Cited by 10 publications

References 30 publications

Infant urinary metabolomic profile in a fatal acute methadone intoxication

Infant urinary metabolomic profile in a fatal acute methadone intoxication

Pediatric opioid fatalities: What can we learn for prevention?

Toxicological and histological analyses for a stillborn delivered by a mother under methadone maintenance therapy

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