title: Randomized controlled trials in pregnancy: scientific and ethical aspects. Exposure to different opioid medications during pregnancy in an intra-individual comparison.
abstract: BACKGROUND
  Chronic medical conditions such as opioid dependence require evidence-based treatment recommendations. However, pregnant women are under-represented in clinical trials. We describe the first within-subject comparison of maternal and neonatal outcomes for methadone- versus buprenorphine-exposed pregnancies. Although methadone is the established treatment of pregnant opioid-dependent women, recent investigations have shown a trend for a milder neonatal abstinence syndrome (NAS) under buprenorphine. However, it is not only the choice of maintenance medication that determines the occurrence of NAS; other factors such as maternal metabolism, illicit substance abuse and nicotine consumption also influence its severity and duration and represent confounding factors in the assessment of randomized clinical trials. CASE SERIES DESCRIPTION: Three women who were part of the European cohort of a randomized, double-blind multi-center trial with a contingency management tool [the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study], each had two consecutive pregnancies and were maintained on either methadone or buprenorphine for their first and then the respective opposite, still-blinded medication for their second pregnancy. Birth measurements, the total neonatal abstinence score, the total amounts of medication used to treat NAS and the days of NAS treatment duration were assessed.
  
  
  RESULTS
  Both medications were effective and safe in reducing illicit opioid relapse and avoiding preterm labor. Methadone maintenance yielded to a significantly higher neonatal birth weight. Data patterns suggest that buprenorphine exposure was associated with lower neonatal abstinence syndrome (NAS) scores. Findings from this unique case series are consistent with earlier reports using between-group analyses.
  
  
  CONCLUSIONS
  Buprenorphine has the potential to become an established treatment alternative to methadone for pregnant opioid-dependent women. Under special consideration of ethical boundaries, psychopharmacological treatment during pregnancy must be addressed as an integral part of clinical research projects in order to optimize treatment for women and neonates.
authors: The Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors: Annemarie
authors: A
authors: Unger
authors: Reinhold
authors: R
authors: Jagsch
authors: Hendree
authors: H
authors: Jones
authors: Amelia
authors: A
authors: Arria
authors: Harald
authors: H
authors: Leitich
authors: Klaudia
authors: K
authors: Rohrmeister
authors: Constantin
authors: C
authors: Aschauer
authors: Berndadette
authors: B
authors: Winklbaur
authors: Andjela
authors: A
authors: Bäwert
authors: Gabriele
authors: G
authors: Fischer
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D001724:Birth Weight / Q000187:drug effects; D002047:Buprenorphine / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008691:Methadone / Q000627:therapeutic use*; D009357:Neonatal Abstinence Syndrome / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D058850:Opiate Substitution Treatment / Q000379:methods; D009293:Opioid-Related Disorders / Q000150:complications / Q000188:drug therapy*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D012720:Severity of Illness Index; D012907:Smoking / Q000453:epidemiology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D002047:Buprenorphine; D008691:Methadone