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

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Abstract

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-old 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. A fully validated toxicological analytical method was developed.

Results

High levels of MTD and EDDP were present in all samples. The EDDP-to-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) diffusely found in the parenchyma.

Conclusions

High levels of MTD and EDDP correlated 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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Authors and Affiliations

  1. Section of Legal Medicine, Università Politecnica delle Marche, Via Conca 71, Ancona, Italy

    Eva Montanari, Raffaele Giorgetti & Adriano Tagliabracci

  2. Pathology Unit, Azienda Unità Sanitaria Locale, IRCCS, Reggio Emilia, Italy

    Maria Paola Bonasoni

  3. Forensic Toxicology Laboratory, Department of Diagnostic Clinical and Public Health Medicine, Università di Modena and Reggio Emilia, Modena, Italy

    Manuela Licata

  4. Regional Antidoping Centre, “A. Bertinaria”, Regione Gonzole 10, Orbassano, Turin, Italy

    Alberto Salomone & Enrico Gerace

  5. Department of Experimental and Clinical Medicine, Hepatobiliary and Abdominal Transplantation Surgery, Università Politecnica delle Marche, Ancona, Italy

    Marco Vivarelli

Authors
  1. Eva Montanari
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  2. Maria Paola Bonasoni
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  3. Manuela Licata
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  4. Alberto Salomone
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Correspondence to Eva Montanari.

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The authors have no financial or other relations that could lead to a conflict of interest.

Ethical approval

In Italy, there is no legislation that forbids the use of human tissues collected during an autopsy, provided that the samples are made anonymous and linked exclusively to codes.

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Montanari, E., Bonasoni, M.P., Licata, M. et al. Toxicological and histological analyses for a stillborn delivered by a mother under methadone maintenance therapy. Forensic Toxicol 36, 514–524 (2018). https://doi.org/10.1007/s11419-017-0402-9

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  • DOI: https://doi.org/10.1007/s11419-017-0402-9

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