{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:02:46Z","timestamp":1790650966168,"version":"4.1.0"},"reference-count":119,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>The two primary classes of opioid substances are morphine and its synthetic derivative, heroin. Opioids can cross the placental barrier, reaching fetal circulation. Therefore, at any gestational age, the fetus is highly exposed to pharmacologically active opioid metabolites and their associated adverse effects. This review aimed to investigate all the studies reported in a timeframe of forty years about prenatal and postnatal outcomes of opioid exposition during pregnancy. Clinical and toxicological aspects, as well as pharmacogenetic and epigenetic research focusing on fetal and infant effects of opioid use during pregnancy together with their medico-legal implications are exposed and discussed.<\/jats:p>","DOI":"10.3390\/children11030278","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T10:47:30Z","timestamp":1708685250000},"page":"278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Fetal and Infant Effects of Maternal Opioid Use during Pregnancy: A Literature Review including Clinical, Toxicological, Pharmacogenomic, and Epigenetic Aspects for Forensic Evaluation"],"prefix":"10.3390","volume":"11","author":[{"given":"Elena","family":"Giovannini","sequence":"first","affiliation":[{"name":"Unit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Paola","family":"Bonasoni","sequence":"additional","affiliation":[{"name":"Unit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, Italy"},{"name":"Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, Via Amendola 2, 42122 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer Paola","family":"Pascali","sequence":"additional","affiliation":[{"name":"Unit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Bini","sequence":"additional","affiliation":[{"name":"Unit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3263-1758","authenticated-orcid":false,"given":"Guido","family":"Pelletti","sequence":"additional","affiliation":[{"name":"Unit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Gualandi","sequence":"additional","affiliation":[{"name":"Institute of Pathology, DAME, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Dal Lago","sequence":"additional","affiliation":[{"name":"Unit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mercati","sequence":"additional","affiliation":[{"name":"Unit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Mariotti","sequence":"additional","affiliation":[{"name":"Unit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia Paola","family":"Pasini","sequence":"additional","affiliation":[{"name":"Unit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iarina Alexandra","family":"Poll","sequence":"additional","affiliation":[{"name":"Unit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2270-9956","authenticated-orcid":false,"given":"Paolo","family":"Fais","sequence":"additional","affiliation":[{"name":"Unit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0889-8545(05)70362-4","article-title":"Opioid dependence during pregnancy. Effects and management","volume":"25","author":"Kaltenbach","year":"1998","journal-title":"Obstet. Gynecol. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1515\/ijamh.2012.016","article-title":"Consequences of prenatal substance use","volume":"24","author":"Sithisarn","year":"2012","journal-title":"Int. J. Adolesc. Med. Health"},{"key":"ref_3","unstructured":"(2022, December 27). National Institute on Drug Abuse, Substance Use While Pregnant and Breast Feeding, Available online: https:\/\/nida.nih.gov\/publications\/research-reports\/substance-use-in-women\/substance-use-while-pregnant-breastfeeding."},{"key":"ref_4","unstructured":"(2022, December 27). Substance Abuse and Mental Health Services Administration 2020 National Survey on Drug Use and Health: Detailed Tables, Available online: https:\/\/www.samhsa.gov\/data\/report\/2020-nsduh-detailed-tables."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1002\/dta.3515","article-title":"Hair testing applied to the assessment of in utero exposure to drugs: Critical analysis of 51 cases of the University Hospital of Verona","volume":"15","author":"Bertaso","year":"2023","journal-title":"Drug Test. Anal."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1111\/j.1360-0443.2012.03828.x","article-title":"Assessment of exposure to drugs of abuse during pregnancy by hair analysis in a Mediterranean island","volume":"107","author":"Friguls","year":"2012","journal-title":"Addiction"},{"key":"ref_7","unstructured":"NIDA (2022, December 27). Heroin DrugFacts, Available online: https:\/\/nida.nih.gov\/publications\/drugfacts\/heroin."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/S0379-0738(02)00160-3","article-title":"Drug abuse\u2019s smallest victims: In utero drug exposure","volume":"128","author":"Huestis","year":"2002","journal-title":"Forensic Sci. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/j.1479-828X.1992.tb01950.x","article-title":"Narcotic addiction in pregnancy with adverse maternal and perinatal outcome","volume":"32","author":"Lam","year":"1992","journal-title":"Aust. N. Z. J. Obstet. Gynaecol."},{"key":"ref_10","unstructured":"British Columbia Centre on Substance Use (2022, December 27). A Guideline for the Clinical Management of Opioid Use Disorder\u2014Pregnancy Supplement. Available online: https:\/\/www.bccsu.ca\/wp-content\/uploads\/2018\/06\/OUD-Pregnancy.pdf."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fishman, B., Daniel, S., Koren, G., Lunenfeld, E., and Levy, A. (2019). Pregnancy outcome following opioid exposure: A cohort study. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0219061"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1097\/00007691-199912000-00002","article-title":"Report on intrauterine drug exposure during second trimester of pregnancy in a heroin-associated death","volume":"21","author":"Skopp","year":"1999","journal-title":"Ther. Drug Monit."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1111\/j.1360-0443.2008.02283.x","article-title":"Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence: A knowledge synthesis for better treatment for women and neonates","volume":"103","author":"Winklbaur","year":"2008","journal-title":"Addiction"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.ejogrb.2023.08.375","article-title":"Use of opioids among pregnant women 1997-2016: A Danish drug utilization study","volume":"289","author":"Rausgaard","year":"2023","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_15","first-page":"22","article-title":"Transplacental methadone exposure and risk of Neonatal Opioid Withdrawal Syndrome","volume":"44","author":"Jing","year":"2023","journal-title":"Pharmacotherapy"},{"key":"ref_16","first-page":"506","article-title":"Heroin addiction and pregnancy","volume":"134","author":"Bashore","year":"1981","journal-title":"West. J. Med."},{"key":"ref_17","unstructured":"Anbalagan, S., and Mendez, M.D. (2023). Neonatal Abstinence Syndrome, StatPearls."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1097\/OGX.0000000000001094","article-title":"Opioid Use in Pregnancy: A Review","volume":"78","author":"Ryan","year":"2023","journal-title":"Obstet. Gynecol. Surv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1093\/aje\/kwab132","article-title":"Ischemic Placental Disease, Preterm Delivery, and Their Association With Opioid Use During Pregnancy","volume":"191","author":"Esposito","year":"2022","journal-title":"Am. J. Epidemiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Borrelli, K.N., Wachman, E.M., Beierle, J.A., Taglauer, E.S., Jain, M., Bryant, C.D., and Zhang, H. (2022). Effect of Prenatal Opioid Exposure on the Human Placental Methylome. Biomedicines, 10.","DOI":"10.3390\/biomedicines10051150"},{"key":"ref_21","first-page":"159","article-title":"Maternal and fetal effects of heroin addiction during pregnancy","volume":"35","author":"Little","year":"1990","journal-title":"J. Reprod. Med."},{"key":"ref_22","first-page":"181","article-title":"Opioid Use Disorder and Pregnancy","volume":"114","author":"Jackson","year":"2017","journal-title":"Mo. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1542\/peds.58.5.681","article-title":"Differential effects of maternal heroin and methadone use on birthweight","volume":"58","author":"Kandall","year":"1976","journal-title":"Pediatrics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"44","DOI":"10.2174\/1874473707666141015215141","article-title":"Opioid neonatal abstinence syndrome: Controversies and implications for practice","volume":"7","author":"Wolff","year":"2014","journal-title":"Curr. Drug Abus. Rev."},{"key":"ref_25","first-page":"127","article-title":"The factors contributing to the risk of sudden infant death syndrome","volume":"15","author":"Athanasakis","year":"2011","journal-title":"Hippokratia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"104997","DOI":"10.1016\/j.earlhumdev.2020.104997","article-title":"Prenatal exposure to methadone or buprenorphine and long-term outcomes: A meta-analysis","volume":"143","author":"Maguire","year":"2020","journal-title":"Early Hum. Dev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"109863","DOI":"10.1016\/j.drugalcdep.2023.109863","article-title":"United States county jail treatment and care of pregnant incarcerated persons with opioid use disorder","volume":"247","author":"Benck","year":"2023","journal-title":"Drug Alcohol Depend."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/j.1465-3362.2010.00176.x","article-title":"Infant mortality among women on a methadone program during pregnancy","volume":"29","author":"Burns","year":"2010","journal-title":"Drug Alcohol Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.ajog.2019.07.022","article-title":"Opioids affect the fetal brain: Reframing the detoxification debate","volume":"221","author":"Caritis","year":"2019","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1111\/apa.13046","article-title":"Maternal use of methadone and risk of sudden neonatal death","volume":"104","author":"Cohen","year":"2015","journal-title":"Acta Paediatr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e20190128","DOI":"10.1542\/peds.2019-0128","article-title":"Prenatal Opioid Exposure: Neurodevelopmental Consequences and Future Research Priorities","volume":"144","author":"Conradt","year":"2019","journal-title":"Pediatrics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1002\/dta.2087","article-title":"Bioanalysis for cocaine, opiates, methadone, and amphetamines exposure detection during pregnancy","volume":"9","author":"Concheiro","year":"2017","journal-title":"Drug. Test. Anal."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1097\/FTD.0b013e31822724f0","article-title":"Methadone, cocaine, opiates, and metabolite disposition in umbilical cord and correlations to maternal methadone dose and neonatal outcomes","volume":"33","author":"Jones","year":"2011","journal-title":"Ther. Drug. Monit."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1111\/j.1471-0528.2008.02073.x","article-title":"Maternal methadone use in pregnancy: Factors associated with the development of neonatal abstinence syndrome and implications for healthcare resources","volume":"116","author":"Dryden","year":"2009","journal-title":"BJOG"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1007\/s10995-021-03307-z","article-title":"Implementation of a prenatal naloxone distribution program to decrease maternal mortality from opioid overdose","volume":"26","author":"Duska","year":"2022","journal-title":"Matern. Child. Health J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.annepidem.2013.05.017","article-title":"Increasing pregnancy-related use of prescribed opioid analgesics","volume":"23","author":"Epstein","year":"2013","journal-title":"Ann. Epidemiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1055\/s-0043-1771388","article-title":"Long-Term Visual and Neurodevelopmental Outcomes in Two Children with Congenital Nystagmus Secondary to Methadone Exposure In utero","volume":"54","author":"Galli","year":"2023","journal-title":"Neuropediatrics"},{"key":"ref_38","first-page":"311","article-title":"Fetal Growth Outcomes in a Cohort of Polydrug- and Opioid-Dependent Patients","volume":"61","author":"Garrison","year":"2016","journal-title":"J. Reprod. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.earlhumdev.2017.01.009","article-title":"Brain morphology in school-aged children with prenatal opioid exposure: A structural MRI study","volume":"106\u2013107","author":"Irnes","year":"2017","journal-title":"Early Hum. Dev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0892-0362(91)90016-P","article-title":"Maternal substance use and subsequent sudden infant death syndrome (SIDS) in offspring","volume":"13","author":"Kandall","year":"1991","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/S0022-3476(05)81554-9","article-title":"Relationship of maternal substance abuse to subsequent sudden infant death syndrome in offspring","volume":"123","author":"Kandall","year":"1993","journal-title":"J. Pediatr."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kushnir, A., Bhavsar, R., Hanna, E., and Hegyi, T. (2023). Neonatal Abstinence Syndrome in Infants with Prenatal Exposure to Methadone versus Buprenorphine. Children, 10.","DOI":"10.3390\/children10061030"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1056\/NEJMc2300439","article-title":"Buprenorphine versus Methadone in Pregnancy","volume":"388","author":"McCarthy","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1093\/jat\/33.7.351","article-title":"Cocaine and opiates use in pregnancy: Detection of drugs in neonatal meconium and urine","volume":"33","author":"Bermejo","year":"2009","journal-title":"J. Anal. Toxicol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1136\/bjophthalmol-2013-303967","article-title":"Visual outcome in infants born to drug-misusing mothers prescribed Methadone in pregnancy","volume":"98","author":"McGlone","year":"2014","journal-title":"Br. J. Ophthalmol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1111\/dmcn.14117","article-title":"Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy: A systematic review and meta-analysis","volume":"61","author":"Monnelly","year":"2019","journal-title":"Dev. Med. Child. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1007\/s11419-017-0402-9","article-title":"Toxicological and histological analyses for a stillborn delivered by a mother under methadone maintenance therapy","volume":"36","author":"Montanari","year":"2018","journal-title":"Forensic Toxicol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s11419-019-00478-x","article-title":"CYP2B6, ABCB1 and OPRM1 profile in a stillborn affected by chronic methadone intoxication","volume":"37","author":"Montanari","year":"2019","journal-title":"Forensic Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/09297049.2023.2272338","article-title":"Associations between social adversity, caregiver psychological factors, and language outcomes in 9.5-year-old children born to women with opioid use disorder","volume":"24","author":"Newbury","year":"2023","journal-title":"Child. Neuropsychol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/jat\/bkad024","article-title":"Longitudinal trends in meconium drug detection in 46 US states between the years 2015 and 2020","volume":"47","author":"Pandya","year":"2023","journal-title":"J. Anal. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3390\/pathophysiology30010004","article-title":"Safety and Efficacy of Buprenorphine-Naloxone in Pregnancy: A Systematic Review of the Literature","volume":"30","author":"Ordean","year":"2023","journal-title":"Pathophysiology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1067\/mpd.2001.111429","article-title":"Estimates of illicit drug use during pregnancy by maternal interview, hair analysis, and meconium analysis","volume":"138","author":"Ostrea","year":"2001","journal-title":"J. Pediatr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"F141","DOI":"10.1136\/adc.2009.181701","article-title":"Maternal methadone therapy increases QTc interval in newborn infants","volume":"96","author":"Parikh","year":"2011","journal-title":"Arch. Dis. Child Fetal Neonatal Ed."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jsgi.2005.11.001","article-title":"Effect of chronic maternal methadone therapy on intrapartum fetal heart rate patterns","volume":"13","author":"Flores","year":"2006","journal-title":"J. Soc. Gynecol. Investig."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1373\/clinchem.2007.091413","article-title":"Buprenorphine and Norbuprenorphine in Hair of Pregnant Women and Their Infants after Controlled Buprenorphine Administration","volume":"53","author":"Robert","year":"2007","journal-title":"Clin. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/npp.2014.147","article-title":"Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn","volume":"40","author":"Ross","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.ajog.2016.12.016","article-title":"Delayed villous maturation in term placentas exposed to opioid maintenance therapy: A retrospective cohort study","volume":"216","author":"Serra","year":"2017","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1118634","DOI":"10.3389\/fped.2023.1118634","article-title":"Executive functioning, behavioural, emotional, and cognitive difficulties in school-aged children prenatally exposed to methadone","volume":"11","author":"Spowart","year":"2023","journal-title":"Front. Pediatr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/S0022-3476(05)80125-8","article-title":"Sudden infant death syndrome in infants of substance-abusing mothers","volume":"117","author":"Ward","year":"1990","journal-title":"J. Pediatr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e20180541","DOI":"10.1542\/peds.2018-0541","article-title":"Neonatal head circumference in newborns with neonatal abstinence syndrome","volume":"143","author":"Towers","year":"2019","journal-title":"Pediatrics"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"906723","DOI":"10.1155\/2014\/906723","article-title":"Maternal opioid drug use during pregnancy and its impact on perinatal morbidity, mortality, and the costs of medical care in the United States","volume":"2014","author":"Whiteman","year":"2014","journal-title":"J. Pregnancy"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"894","DOI":"10.3174\/ajnr.A1957","article-title":"White matter characteristics and cognition in prenatally opiate- and polysubstance-exposed children: A diffusion tensor imaging study","volume":"31","author":"Walhovd","year":"2010","journal-title":"Am. J. Neuroradiol."},{"key":"ref_63","first-page":"89","article-title":"A Swedish Population-based Study of Adverse Birth Outcomes among Pregnant Women Treated with Buprenorphine or methadone: Preliminary Findings","volume":"10","author":"Wurst","year":"2016","journal-title":"Subst. Abus."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1111\/add.13462","article-title":"Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: A systematic review and meta-analysis of safety in the mother, fetus and child","volume":"111","author":"Zedler","year":"2016","journal-title":"Addiction"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1177\/1753495X20971163","article-title":"Opioid use in pregnancy: An emerging health crisis","volume":"14","author":"Zipursky","year":"2021","journal-title":"Obstet. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1002\/cpt.2149","article-title":"Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy","volume":"110","author":"Crews","year":"2021","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_67","unstructured":"(2022, December 28). CPIC Guideline for Opioids and CYP2D6, OPRM1, and COMT. Available online: https:\/\/cpicpgx.org\/guidelines\/guideline-for-codeine-and-cyp2d6\/."},{"key":"ref_68","first-page":"675","article-title":"The Impact of Pharmacogenetics on Pharmacokinetics and Pharmacodynamics in Neonates and Infants: A Systematic Review","volume":"15","author":"Flint","year":"2022","journal-title":"Pharmgenom. Pers. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"721","DOI":"10.2174\/138920012800840392","article-title":"Pharmacogenetics of opioids for the treatment of acute maternal pain during pregnancy and lactation","volume":"13","author":"Madadi","year":"2012","journal-title":"Curr. Drug Metab."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1055\/s-0037-1600917","article-title":"Variations in Infant CYP2B6 Genotype Associated with the Need for Pharmacological Treatment for Neonatal Abstinence Syndrome in Infants of Methadone-Maintained Opioid-Dependent Mothers","volume":"34","author":"Mactier","year":"2017","journal-title":"Am. J. Perinatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1002\/jcph.1811","article-title":"Opioid Treatment for Neonatal Opioid Withdrawal Syndrome: Current Challenges and Future Approaches","volume":"61","author":"McPhail","year":"2021","journal-title":"J. Clin. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1002\/jcph.696","article-title":"Mechanistic population pharmacokinetics of morphine in neonates with abstinence syndrome after oral administration of diluted tincture of opium","volume":"56","author":"Liu","year":"2016","journal-title":"J. Clin. Pharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/17425255.2021.1837112","article-title":"Pharmacotherapy of neonatal opioid withdrawal syndrome: A review of pharmacokinetics and pharmacodynamics. Expert","volume":"17","author":"McPhail","year":"2021","journal-title":"Opin. Drug Metab. Toxicol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1001\/jama.2013.3411","article-title":"Association of OPRM1 and COMT single-nucleotide polymorphisms with hospital length of stay and treatment of neonatal abstinence syndrome","volume":"309","author":"Wachman","year":"2013","journal-title":"JAMA"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Albano, G.D., La Spina, C., Pitingaro, W., Milazzo, V., Triolo, V., Argo, A., Malta, G., and Zerbo, S. (2023). Intrauterine and Neonatal Exposure to Opioids: Toxicological, Clinical, and Medico-Legal Issues. Toxics, 11.","DOI":"10.3390\/toxics11010062"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.forsciint.2014.09.014","article-title":"Contribution of in utero drug exposure when interpreting hair results in young children","volume":"249","author":"Kintz","year":"2015","journal-title":"Forensic Sci. Int."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/S0140-6736(06)69255-6","article-title":"Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother","volume":"368","author":"Koren","year":"2006","journal-title":"Lancet"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/clpt.2008.157","article-title":"Pharmacogenetics of neonatal opioid toxicity following maternal use of codeine during breastfeeding: A case-control study","volume":"85","author":"Madadi","year":"2009","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"151","DOI":"10.5055\/jom.2013.0156","article-title":"Codeine-associated pediatric deaths despite using recommended dosing guidelines: Three case reports","volume":"9","author":"Friedrichsdorf","year":"2013","journal-title":"J. Opioid. Manag."},{"key":"ref_80","first-page":"33","article-title":"Safety of codeine during breastfeeding: Fatal morphine poisoning in the breastfed neonate of a mother prescribed codeine","volume":"53","author":"Madadi","year":"2007","journal-title":"Can. Fam. Physician"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/clpt.2011.280","article-title":"Prediction of codeine toxicity in infants and their mothers using a novel combination of maternal genetic markers","volume":"91","author":"Sistonen","year":"2012","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1124\/dmd.110.033878","article-title":"CYP2D6 mediates 4-hydroxylation of clonidine in vitro: Implication for pregnancy-induced changes in clonidine clearance","volume":"38","author":"Claessens","year":"2010","journal-title":"Drug Metab. Dispos."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1208\/s12248-020-00541-1","article-title":"Application of Model Informed Precision Dosing to Address the Impact of Pregnancy Stage and CYP2D6 Phenotype on Foetal Morphine Exposure","volume":"23","author":"Badaoui","year":"2021","journal-title":"AAPS J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/ckj\/sfs099","article-title":"Acute kidney injury in a preterm infant homozygous for the C3435T polymorphism in the ABCB1 gene given oral morphine","volume":"5","author":"Pogliani","year":"2012","journal-title":"Clin. Kidney J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1097\/FTD.0000000000000301","article-title":"Genetic Predisposition to Poor Opioid Response in Preterm Infants: Impact of KCNJ6 and COMT Polymorphisms on Pain Relief After Endotracheal Intubation","volume":"38","author":"Elens","year":"2016","journal-title":"Ther. Drug Monit."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.2217\/pgs.14.100","article-title":"Rescue morphine in mechanically ventilated newborns associated with combined OPRM1 and COMT genotype","volume":"15","author":"Matic","year":"2014","journal-title":"Pharmacogenomics"},{"key":"ref_87","first-page":"S463","article-title":"Sufentanil and midazolam dosing and pharmacogenetic factors in pediatric analgosedation and withdrawal syndrome","volume":"65","author":"Posch","year":"2016","journal-title":"Physiol. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.2217\/pgs.14.115","article-title":"Effect of UGT2B7 \u2212900G>A (\u2212842G>A; rs7438135) on morphine glucuronidation in preterm newborns: Results from a pilot cohort","volume":"15","author":"Matic","year":"2014","journal-title":"Pharmacogenomics"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1097\/FTD.0000000000000307","article-title":"SLC22A1\/OCT1 Genotype Affects O-desmethyltramadol Exposure in Newborn Infants","volume":"38","author":"Matic","year":"2016","journal-title":"Ther. Drug Monit."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1007\/s00204-023-03563-8","article-title":"Neonatal opioid toxicity: Opioid withdrawal (abstinence) syndrome with emphasis on pharmacogenomics and respiratory depression","volume":"97","author":"Baldo","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Dennis, B.B., Bawor, M., and Thabane, L. (2014). Impact of ABCB1 and CYP2B6 genetic polymorphisms on methadone metabolism, dose and treatment response in patients with opioid addiction: A systematic review and meta-analysis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086114"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.jpeds.2014.05.040","article-title":"Epigenetic variation in the mu-opioid receptor gene in infants with neonatal abstinence syndrome","volume":"165","author":"Wachman","year":"2014","journal-title":"J. Pediatr."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e12476","DOI":"10.1111\/gbb.12476","article-title":"Epigenetic variation in OPRM1 gene in opioid-exposed mother-infant dyads","volume":"17","author":"Wachman","year":"2018","journal-title":"Genes Brain Behav."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Committee Opinion No (2017). Opioid Use and Opioid Use Disorder in Pregnancy. Obstet. Gynecol., 130, 488\u2013489.","DOI":"10.1097\/AOG.0000000000002229"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.bpobgyn.2022.07.008","article-title":"Epidemiology of opioid use in pregnancy","volume":"85","author":"Cook","year":"2022","journal-title":"Best Pract. Res Clin. Obstet. Gynaecol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s40501-020-00221-z","article-title":"Buprenorphine dosing for the treatment of opioid use disorder through pregnancy and postpartum","volume":"7","author":"Martin","year":"2020","journal-title":"Curr. Treat. Options Psychiatry"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.ogc.2022.10.015","article-title":"Opioids and Opioid Use Disorder in Pregnancy","volume":"50","author":"Sanjanwala","year":"2023","journal-title":"Obstet. Gynecol. Clin. N. Am."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1097\/AOG.0000000000003279","article-title":"Pregnancy-Associated Death in Utah: Contribution of Drug-Induced Deaths","volume":"133","author":"Smid","year":"2019","journal-title":"Obstet. Gynecol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.11124\/JBIES-22-00414","article-title":"Procedural pain assessment in neonates at risk of neonatal opioid withdrawal syndrome: A scoping review protocol","volume":"21","author":"Lavergne","year":"2023","journal-title":"JBI Evid. Synth."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ejogrb.2023.05.019","article-title":"Harmful effects of opioid use in pregnancy: A scientific review commissioned by the European Board and College of obstetrics and gynaecology (EBCOG)","volume":"286","author":"Vella","year":"2023","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1161\/HYPERTENSIONAHA.122.20262","article-title":"Prenatal Morphine Exposure Increases Cardiovascular Disease Risk and Programs Neurogenic Hypertension in the Adult Offspring","volume":"80","author":"Ahmed","year":"2023","journal-title":"Hypertension"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"110803","DOI":"10.1016\/j.brainresbull.2023.110803","article-title":"Enhancement of neuronal excitability in the medial prefrontal cortex following prenatal morphine exposure","volume":"204","author":"Alaee","year":"2023","journal-title":"Brain Res. Bull."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Jullien, S. (2021). Sudden infant death syndrome prevention. BMC Pediatr., 21.","DOI":"10.1186\/s12887-021-02536-z"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e118","DOI":"10.3928\/19382359-20180221-03","article-title":"Sudden Infant Death Syndrome: A Review","volume":"47","author":"Goldberg","year":"2018","journal-title":"Pediatr. Ann."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1136\/jclinpath-2016-204199","article-title":"Long QT syndrome and sudden unexpected infant death","volume":"70","year":"2017","journal-title":"J. Clin. Pathol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Ioakeimidis, N.S., Papamitsou, T., Meditskou, S., and Iakovidou-Kritsi, Z. (2017). Sudden infant death syndrome due to long QT syndrome: A brief review of the genetic substrate and prevalence. J. Biol. Res., 24.","DOI":"10.1186\/s40709-017-0063-1"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1002\/cpt.1249","article-title":"Influence of OCT1 Ontogeny and Genetic Variation on Morphine Disposition in Critically Ill Neonates: Lessons From PBPK Modeling and Clinical Study","volume":"105","author":"Hahn","year":"2019","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1038\/clpt.2009.151","article-title":"Risk to the breast-fed neonate from codeine treatment to the mother: A quantitative mechanistic modeling study","volume":"86","author":"Willmann","year":"2009","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1891\/0730-0832.32.6.419","article-title":"Oral clonidine in the management of acquired opioid dependency","volume":"32","author":"Beaulieu","year":"2013","journal-title":"Neonatal Netw."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1124\/dmd.108.021873","article-title":"Developmental changes in human liver CYP2D6 expression","volume":"36","author":"Stevens","year":"2008","journal-title":"Drug Metab. Dispos."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1002\/jcph.1592","article-title":"Influence of MRP3 Genetics and Hepatic Expression Ontogeny for Morphine Disposition in Neonatal and Pediatric Patients","volume":"60","author":"Hahn","year":"2020","journal-title":"J. Clin. Pharmacol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1097\/FPC.0b013e32835cb2e2","article-title":"Contribution of CYP2B6 alleles in explaining extreme (S)- methadone plasma levels: A CYP2B6 gene resequencing study","volume":"23","author":"Dobrinas","year":"2013","journal-title":"Pharmacogenet. Genom."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1124\/dmd.112.050625","article-title":"Methadone N-demethylation by the common CYP2B6 allelic variant CYP2B6.6","volume":"41","author":"Gadel","year":"2013","journal-title":"Drug Metab. Dispos."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1097\/ALN.0000000000000867","article-title":"Methadone pharmacogenetics: CYP2B6 polymorphisms determine plasma concentrations, clearance, and metabolism","volume":"123","author":"Kharasch","year":"2015","journal-title":"Anesthesiology"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1097\/FTD.0000000000000437","article-title":"Combined effect of CYP2B6 genotype and other candidate genes on a steady-state serum concentration of methadone in opioid maintenance treatment","volume":"39","author":"Kringen","year":"2017","journal-title":"Ther. Drug Monit."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/clpt.2010.127","article-title":"OPRM1 and CYP2B6 gene variants as risk factors in methadone -related deaths","volume":"88","author":"Bunten","year":"2010","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/anatox\/35.7.431","article-title":"Interindividual variability in the prevalence of OPRM1 and CYP2B6 gene variations may identify drug-susceptible populations","volume":"35","author":"Bunten","year":"2011","journal-title":"J. Anal. Toxicol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/npp.2008.108","article-title":"Increased OPRM1 DNA methylation in lymphocytes of methadone -maintained former heroin addicts","volume":"34","author":"Nielsen","year":"2009","journal-title":"Neuropsychopharmacology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.neuropharm.2013.06.016","article-title":"The impact of exposure to addictive drugs on future generations: Physiological and behavioral effects","volume":"76","author":"Vassoler","year":"2014","journal-title":"Neuropharmacology"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/11\/3\/278\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:04:03Z","timestamp":1760105043000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/11\/3\/278"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,23]]},"references-count":119,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["children11030278"],"URL":"https:\/\/doi.org\/10.3390\/children11030278","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,23]]}}}