Journal Mobile Options
Table of Contents
Vol. 16, No. 2, 2010
Issue release date: March 2010
Section title: Research Report
Free Access
Eur Addict Res 2010;16:99–107
(DOI:10.1159/000284683)

Clinical Characteristics of Central European and North American Samples of Pregnant Women Screened for Opioid Agonist Treatment

Unger A.S. · Martin P.R. · Kaltenbach K. · Stine S.M. · Heil S.H. · Jones H.E. · Arria A.M. · Coyle M.G. · Selby P. · Fischer G.
Department of Psychiatry, University Hospital of Vienna, Vienna, Austria
email Corresponding Author

Abstract

Background: Little comparable information is available regarding clinical characteristics of opioid-dependent women from different countries. In the present study, women from the USA, Canada and a Central European country, Austria, screened for participation in the Maternal Opioid Treatment Human Experimental Research study, were compared with respect to their demographic and addiction histories. Methods: Pregnant women (n = 1,074) were screened for study participation using uniformed clinical criteria and instruments. The screening results were compared with regard to exclusion, demographics, drug use, and psychosocial and treatment histories. Results: Compared to the screened US and Canadian women, Austrian women were more likely to be younger (p < 0.001), white (p < 0.001), had significantly lower levels of educational attainment (p < 0.001), were less likely to use opioids daily (p < 0.001) and more likely to have been prescribed buprenorphine (p < 0.001). Compared to both rural and urban US groups, the Austrian group was less likely to have legal issues (p < 0.001) and was younger when first prescribed agonist medication (p < 0.001). Conclusion: The differences between North American and European groups may offer unique insights concerning treatment and pregnancy outcomes for opioid-dependent pregnant women.

© 2010 S. Karger AG, Basel


  

Key Words

  • Pregnancy
  • Opioid dependence
  • Methadone
  • Buprenorphine

References

  1. van den Brink W, Goppel M, van Ree J: Management of opioid dependence. Curr Opin Psychiatry 2003;16:297–304.

    External Resources

  2. Winklbaur B, Kopf N, Ebner N, Jung E, Thau K, Fischer G: 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. Addiction 2008;103:1429–1440.
  3. Jones HE, O’Grady KE, Malfi D, Tuten M: Methadone maintenance vs methadone taper during pregnancy: maternal and neonatal outcomes. Am J Addict 2008;17:372–386.
  4. Kaltenbach K, Silverman NS, Wapner RJ: Methadone maintenance during pregnancy; in Parrino M (ed): State Methadone Guidelines. Treatment Improvement Protocol (TIP), ser 1. Rockville, Center for Substance Abuse Treatment, Substance Abuse and Mental Health Administration, US Department of Health and Human Services, 1993, chapt 9, pp 85–93.
  5. Johnson RE, Jones HE, Fischer G: Use of buprenorphine in pregnancy: patient management and effects on the neonate. Drug Alcohol Depend 2003;70:87–101.

    External Resources

  6. Jones HE, Johnson RE, Jasinski DR, O’Grady KE, Chisholm CA, Choo RE, Crocetti M, Dudas R, Harrow C, Huestis MA, Jansson LM, Lantz M, Lester BM, Milio L: Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome. Drug Alcohol Depend 2005;79:1–10.
  7. Ministry of Health Canada: Therapeutic products directorate guidelines: the use of opioids in the management of opioid dependence. 1992. http://dsp-psd.communication.gc.ca/Collection/H42-2-57-1992E.pdf (accessed August 31, 2009).
  8. Lejeune C, Simmat-Durand L, Gourarier L, Aubisson S: Prospective multicenter observational study of 260 infants born to 259 opiate-dependent mothers on methadone or high-dose buprenorphine substitution. Drug Alcohol Depend 2006;82:250–257.
  9. Fischer G, Johnson RE, Eder H, Jagsch R, Peternell A, Weninger M, Langer M, Aschauer H: Treatment of opioid-dependent pregnant women with buprenorphine. Addiction 2000;95:239–244.
  10. Schindler SD, Eder H, Ortner R, Rohrmeister K, Langer M, Fischer G: Neonatal outcome following buprenorphine maintenance during conception and throughout pregnancy. Addiction 2003;98:103–110.
  11. Fudala PJ, Bridge TP, Herbert S, Williford WO, Chiang CN, Jones K, et al: Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone. N Engl J Med 2003;349:949–958.
  12. Jones HE, Martin PR, Heil SH, Kaltenbach K, Selby P, Coyle MG, Stine SM, O’Grady KE, Arria AM, Fischer G: Treatment of opioid-dependent pregnant women: clinical and research issues. J Subst Abuse Treat 2008;35:245–259.
  13. Kidorf M, Neufeld K, Brooner R: Combining stepped-care approaches with behavioral reinforcement to motivate employment in opioid-dependent outpatients. Subst Use Misuse 2004;39:2215–2238.
  14. O’Brien CP, McLellan AT: Myths about the treatment of addiction. Lancet 1996;347:237–240.
  15. Ryan CF, White JM: Health status at entry to methadone maintenance treatment using the SF-36 health survey questionnaire. Addiction 1996;91:39–45.
  16. McLellan AT: Psychiatric severity as a predictor of outcome from substance abuse treatments; in Meyer RE (ed): Psychopathology and Addictive Disorders. New York, Guilford, 1986, pp 97–139.
  17. Laken MP, Ager JW: Effects of case management on retention in prenatal substance abuse treatment. Am J Drug Alcohol Abuse 1996;22:439–448.
  18. Shepard E, Blackley PR: US drug control policies: federal spending on law enforcement versus treatment in public health outcomes. J Drug Issues 2004;34:771–786.

    External Resources

  19. Woody GE: New horizons: sustained-release morphine as agonist treatment. Addiction 2005;100:1758–1759.
  20. Kraigher D, Jagsch R, Gombas W, Ortner R, Eder H, Primorac A, Fischer G: Use of slow-release oral morphine for the treatment of opioid dependence. Eur Addict Res 2005;11:145–151.
  21. Eder H, Jagsch R, Kraigher D, Primorac A, Ebner N, Fischer G: Comparative study of the effectiveness of slow-release morphine and methadone for opioid maintenance therapy. Addiction 2005;100:1101–1109.
  22. Winklbaur B, Jagsch R, Ebner N, Thau K, Fischer G: Quality of life in patients receiving opioid maintenance therapy: a comparative study of slow-release morphine versus methadone treatment. Eur Addict Res 2008;14:99–105.
  23. Aeschbach Jachmann C, Jagsch R, Winklbaur B, Matzenauer C, Fischer G: Office-based treatment in opioid dependence: a critical survey of prescription practices for opioid maintenance medications and concomitant benzodiazepines in Vienna, Austria. Eur Addict Res 2008;14:206–212.
  24. Pelet A, Doll S, Huissoud T, Resplendino J, Besson J, Favrat B: Methadone maintenance treatment (MMT) in general practice or in specialized centers: profile of patients in the Swiss canton of Vaud. Am J Drug Alcohol Abuse 2007;33:665–674.
  25. Feroni I, Peretti-Watel P, Masut A, Coudert C, Paraponaris A, Obadia Y: French general practitioners prescribing high-dosage buprenorphine maintenance treatment: is the existing training (good) enough? Addict Behav 2005;30:187–191.
  26. Ortner R, Jagsch R, Schindler SD, Primorac A, Fischer G, General Practitioner Addiction Team: Buprenorphine maintenance: office-based treatment with addiction clinic support. Eur Addict Res 2004;10:105–111.
  27. O’Connor PG: Methods of detoxification and their role in treating patients with opioid dependence. JAMA 2005;294:961–963.
  28. Kerr T, Marsh D, Li K, Montaner J, Wood E: Factors associated with methadone maintenance therapy use among a cohort of polysubstance-using injection drug users in Vancouver. Drug Alcohol Depend 2005;80:329–335.
  29. Brooner R, Kidorf M, King V, Beilenson P, Svikis D, Vlahov D: Drug abuse treatment success among needle exchange participants. Public Health Rep 1998;113:129–139.

    External Resources

  30. Heil SH, Sigmon SC, Jones HE, Wagner M: Comparison of characteristics of opioid- using pregnant women in rural and urban settings. Am J Drug Alcohol Abuse 2008;34:463–471.
  31. Friedmann PD, D’Aunno TA: Medical and psychosocial services in drug abuse treatment: do stronger linkages promote client utilization? Health Serv Res 2000;35:443–465.
  32. Strathdee SA, Ricketts EP, Huettner S, Cornelius L, Bishai D, Havens JR, Beilenson P, Rapp C, Lloyd JJ, Latkin CA: Facilitating entry into drug treatment among injection drug users referred from a needle exchange program: results from a community-based behavioral intervention trial. Drug Alcohol Depend 2006;83:225–232.
  33. Friedmann PD, Lemon SC, Stein MD: Transportation and retention in outpatient drug abuse treatment programs. J Subst Abuse Treat 2001;21:97–103.
  34. Day E, George S: Management of drug misuse in pregnancy. Adv Psychiatr Treat 2005;11:253–261.

    External Resources

  35. European Monitoring Centre for Drugs and Drug Addiction: Annual report on the state of the drugs problem in the European Union. 2008. www.emcdda.europa.eu/attachements.cfm/att_64227_EN_EMCDDA_AR08_en.pdf (accessed August 31, 2009).
  36. Fischer G, Ortner R, Rohrmeister K, Jagsch R, Baewert A, Langer M, Aschauer H: Methadone versus buprenorphine in pregnant addicts: a double-blind, double-dummy comparison study. Addiction 2006;101:275–281.
  37. Brands B, Blake J, Marsh DC, Sproule B, Jeyapalan R, Li S: The impact of benzodiazepine use on methadone maintenance treatment outcomes. J Addict Dis 2008;27:37–48.
  38. Clark NC, Dietze P, Lenne MG, Redman JR: Effect of opioid substitution therapy on alcohol metabolism. J Subst Abuse Treat 2006;30:191–196.
  39. DeMaria PA Jr, Sterling R, Weinstein SP: The effect of stimulant and sedative use on treatment outcome of patients admitted to methadone maintenance treatment. Am J Addict 2000;9:145–153.
  40. Ghitza UE, Epstein DH, Preston KL: Self- report of illicit benzodiazepine use on the Addiction Severity Index predicts treatment outcome. Drug Alcohol Depend 2008;97:150–157.
  41. Weizman T, Gelkopf M, Melamed Y, Adelson M, Bleich A: Treatment of benzodiazepine dependence in methadone maintenance treatment patients: a comparison of two therapeutic modalities and the role of psychiatric co-morbidity. Aust N Z J Psychiatry 2003;37:458–463.
  42. Chang Y, Moody D: Effect of benzodiazepines on the metabolism of buprenorphine in human liver microsomes. Eur J Clin Pharmacol 2005;60:875–881.
  43. Gueye PN, Megarbane B, Borron SW, Adnet F, Galliot-Guilley M, Ricordel I, Tourneau J, Goldgran-Toledano D, Baud FJ: Trends in opiate and opioid poisonings in addicts in north-east Paris and suburbs, 1995–1999. Addiction 2002;97:1295–1304.
  44. Lintzeris N, Mitchell TB, Bond AJ, Nestor L, Strang J: Pharmacodynamics of diazepam co-administered with methadone or buprenorphine under high-dose conditions in opioid-dependent patients. Drug Alcohol Depend 2007;91:187–194.
  45. Chan GM, Stajic M, Marker EK, Hoffman RS, Nelson LS: Testing positive for methadone and either a tricyclic antidepressant or a benzodiazepine is associated with an accidental overdose death: analysis of medical examiner data. Acad Emerg Med 2006;13:543–547.
  46. Mikolaenko I, Robinson CA, Davis GG: A review of methadone deaths in Jefferson County, Alabama. Am J Forensic Med Pathol 2002;29:299–304.

    External Resources

  47. Schifano F, Corkery J, Gilvarry E, Deluca P, Oyefeso A, Ghodse AH: Buprenorphine mortality, seizures and prescription data in the UK, 1980–2002. Hum Psychopharmacol 2005;20:343–348.
  48. Shah N, Lathrop SL, Landen MG: Unintentional methadone-related overdose death in New Mexico (USA) and implications for surveillance, 1998–2002. Addiction 2005;100:176–188.
  49. Martin PR, Arria AM, Fischer G, Kaltenbach K, Heil SH, Stine SM, Coyle MG, Selby P, Jones HE: Psychopharmacologic management of opioid-dependent women during pregnancy. Am J Addict 2009;18:148–156.
  50. Dolovich L, Addis A, Vaillancourt R, Power B, Koren G, Einarson T: Benzodiazepine use in pregnancy and major malformations or oral cleft: meta-analysis of cohort and case-control studies. BMJ 1998;317:839–843.
  51. Seligman N, Salva N, Hayes E, Dysart K, Pequignot E, Baxter J: Predicting length of treatment for neonatal abstinence syndrome in methadone-exposed neonates. Am J Obstet Gynecol 2008;199:396e1–396e7.

  

Author Contacts

Annemarie S. Unger
University Hospital of Vienna, Department of Psychiatry
Währinger Gürtel 18–20, AT–1090 Vienna (Austria)
Tel. +43 1 40400 3547, Fax +43 1 40400 3388
E-Mail annemarie.unger@meduniwien.ac.at

  

Article Information

Published online: February 17, 2010
Number of Print Pages : 9
Number of Figures : 0, Number of Tables : 2, Number of References : 51

  

Publication Details

European Addiction Research

Vol. 16, No. 2, Year 2010 (Cover Date: March 2010)

Journal Editor: van den Brink W. (Amsterdam), Haasen C. (Hamburg)
ISSN: 1022-6877 (Print), eISSN: 1421-9891 (Online)

For additional information: http://www.karger.com/EAR


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References

  1. van den Brink W, Goppel M, van Ree J: Management of opioid dependence. Curr Opin Psychiatry 2003;16:297–304.

    External Resources

  2. Winklbaur B, Kopf N, Ebner N, Jung E, Thau K, Fischer G: 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. Addiction 2008;103:1429–1440.
  3. Jones HE, O’Grady KE, Malfi D, Tuten M: Methadone maintenance vs methadone taper during pregnancy: maternal and neonatal outcomes. Am J Addict 2008;17:372–386.
  4. Kaltenbach K, Silverman NS, Wapner RJ: Methadone maintenance during pregnancy; in Parrino M (ed): State Methadone Guidelines. Treatment Improvement Protocol (TIP), ser 1. Rockville, Center for Substance Abuse Treatment, Substance Abuse and Mental Health Administration, US Department of Health and Human Services, 1993, chapt 9, pp 85–93.
  5. Johnson RE, Jones HE, Fischer G: Use of buprenorphine in pregnancy: patient management and effects on the neonate. Drug Alcohol Depend 2003;70:87–101.

    External Resources

  6. Jones HE, Johnson RE, Jasinski DR, O’Grady KE, Chisholm CA, Choo RE, Crocetti M, Dudas R, Harrow C, Huestis MA, Jansson LM, Lantz M, Lester BM, Milio L: Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome. Drug Alcohol Depend 2005;79:1–10.
  7. Ministry of Health Canada: Therapeutic products directorate guidelines: the use of opioids in the management of opioid dependence. 1992. http://dsp-psd.communication.gc.ca/Collection/H42-2-57-1992E.pdf (accessed August 31, 2009).
  8. Lejeune C, Simmat-Durand L, Gourarier L, Aubisson S: Prospective multicenter observational study of 260 infants born to 259 opiate-dependent mothers on methadone or high-dose buprenorphine substitution. Drug Alcohol Depend 2006;82:250–257.
  9. Fischer G, Johnson RE, Eder H, Jagsch R, Peternell A, Weninger M, Langer M, Aschauer H: Treatment of opioid-dependent pregnant women with buprenorphine. Addiction 2000;95:239–244.
  10. Schindler SD, Eder H, Ortner R, Rohrmeister K, Langer M, Fischer G: Neonatal outcome following buprenorphine maintenance during conception and throughout pregnancy. Addiction 2003;98:103–110.
  11. Fudala PJ, Bridge TP, Herbert S, Williford WO, Chiang CN, Jones K, et al: Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone. N Engl J Med 2003;349:949–958.
  12. Jones HE, Martin PR, Heil SH, Kaltenbach K, Selby P, Coyle MG, Stine SM, O’Grady KE, Arria AM, Fischer G: Treatment of opioid-dependent pregnant women: clinical and research issues. J Subst Abuse Treat 2008;35:245–259.
  13. Kidorf M, Neufeld K, Brooner R: Combining stepped-care approaches with behavioral reinforcement to motivate employment in opioid-dependent outpatients. Subst Use Misuse 2004;39:2215–2238.
  14. O’Brien CP, McLellan AT: Myths about the treatment of addiction. Lancet 1996;347:237–240.
  15. Ryan CF, White JM: Health status at entry to methadone maintenance treatment using the SF-36 health survey questionnaire. Addiction 1996;91:39–45.
  16. McLellan AT: Psychiatric severity as a predictor of outcome from substance abuse treatments; in Meyer RE (ed): Psychopathology and Addictive Disorders. New York, Guilford, 1986, pp 97–139.
  17. Laken MP, Ager JW: Effects of case management on retention in prenatal substance abuse treatment. Am J Drug Alcohol Abuse 1996;22:439–448.
  18. Shepard E, Blackley PR: US drug control policies: federal spending on law enforcement versus treatment in public health outcomes. J Drug Issues 2004;34:771–786.

    External Resources

  19. Woody GE: New horizons: sustained-release morphine as agonist treatment. Addiction 2005;100:1758–1759.
  20. Kraigher D, Jagsch R, Gombas W, Ortner R, Eder H, Primorac A, Fischer G: Use of slow-release oral morphine for the treatment of opioid dependence. Eur Addict Res 2005;11:145–151.
  21. Eder H, Jagsch R, Kraigher D, Primorac A, Ebner N, Fischer G: Comparative study of the effectiveness of slow-release morphine and methadone for opioid maintenance therapy. Addiction 2005;100:1101–1109.
  22. Winklbaur B, Jagsch R, Ebner N, Thau K, Fischer G: Quality of life in patients receiving opioid maintenance therapy: a comparative study of slow-release morphine versus methadone treatment. Eur Addict Res 2008;14:99–105.
  23. Aeschbach Jachmann C, Jagsch R, Winklbaur B, Matzenauer C, Fischer G: Office-based treatment in opioid dependence: a critical survey of prescription practices for opioid maintenance medications and concomitant benzodiazepines in Vienna, Austria. Eur Addict Res 2008;14:206–212.
  24. Pelet A, Doll S, Huissoud T, Resplendino J, Besson J, Favrat B: Methadone maintenance treatment (MMT) in general practice or in specialized centers: profile of patients in the Swiss canton of Vaud. Am J Drug Alcohol Abuse 2007;33:665–674.
  25. Feroni I, Peretti-Watel P, Masut A, Coudert C, Paraponaris A, Obadia Y: French general practitioners prescribing high-dosage buprenorphine maintenance treatment: is the existing training (good) enough? Addict Behav 2005;30:187–191.
  26. Ortner R, Jagsch R, Schindler SD, Primorac A, Fischer G, General Practitioner Addiction Team: Buprenorphine maintenance: office-based treatment with addiction clinic support. Eur Addict Res 2004;10:105–111.
  27. O’Connor PG: Methods of detoxification and their role in treating patients with opioid dependence. JAMA 2005;294:961–963.
  28. Kerr T, Marsh D, Li K, Montaner J, Wood E: Factors associated with methadone maintenance therapy use among a cohort of polysubstance-using injection drug users in Vancouver. Drug Alcohol Depend 2005;80:329–335.
  29. Brooner R, Kidorf M, King V, Beilenson P, Svikis D, Vlahov D: Drug abuse treatment success among needle exchange participants. Public Health Rep 1998;113:129–139.

    External Resources

  30. Heil SH, Sigmon SC, Jones HE, Wagner M: Comparison of characteristics of opioid- using pregnant women in rural and urban settings. Am J Drug Alcohol Abuse 2008;34:463–471.
  31. Friedmann PD, D’Aunno TA: Medical and psychosocial services in drug abuse treatment: do stronger linkages promote client utilization? Health Serv Res 2000;35:443–465.
  32. Strathdee SA, Ricketts EP, Huettner S, Cornelius L, Bishai D, Havens JR, Beilenson P, Rapp C, Lloyd JJ, Latkin CA: Facilitating entry into drug treatment among injection drug users referred from a needle exchange program: results from a community-based behavioral intervention trial. Drug Alcohol Depend 2006;83:225–232.
  33. Friedmann PD, Lemon SC, Stein MD: Transportation and retention in outpatient drug abuse treatment programs. J Subst Abuse Treat 2001;21:97–103.
  34. Day E, George S: Management of drug misuse in pregnancy. Adv Psychiatr Treat 2005;11:253–261.

    External Resources

  35. European Monitoring Centre for Drugs and Drug Addiction: Annual report on the state of the drugs problem in the European Union. 2008. www.emcdda.europa.eu/attachements.cfm/att_64227_EN_EMCDDA_AR08_en.pdf (accessed August 31, 2009).
  36. Fischer G, Ortner R, Rohrmeister K, Jagsch R, Baewert A, Langer M, Aschauer H: Methadone versus buprenorphine in pregnant addicts: a double-blind, double-dummy comparison study. Addiction 2006;101:275–281.
  37. Brands B, Blake J, Marsh DC, Sproule B, Jeyapalan R, Li S: The impact of benzodiazepine use on methadone maintenance treatment outcomes. J Addict Dis 2008;27:37–48.
  38. Clark NC, Dietze P, Lenne MG, Redman JR: Effect of opioid substitution therapy on alcohol metabolism. J Subst Abuse Treat 2006;30:191–196.
  39. DeMaria PA Jr, Sterling R, Weinstein SP: The effect of stimulant and sedative use on treatment outcome of patients admitted to methadone maintenance treatment. Am J Addict 2000;9:145–153.
  40. Ghitza UE, Epstein DH, Preston KL: Self- report of illicit benzodiazepine use on the Addiction Severity Index predicts treatment outcome. Drug Alcohol Depend 2008;97:150–157.
  41. Weizman T, Gelkopf M, Melamed Y, Adelson M, Bleich A: Treatment of benzodiazepine dependence in methadone maintenance treatment patients: a comparison of two therapeutic modalities and the role of psychiatric co-morbidity. Aust N Z J Psychiatry 2003;37:458–463.
  42. Chang Y, Moody D: Effect of benzodiazepines on the metabolism of buprenorphine in human liver microsomes. Eur J Clin Pharmacol 2005;60:875–881.
  43. Gueye PN, Megarbane B, Borron SW, Adnet F, Galliot-Guilley M, Ricordel I, Tourneau J, Goldgran-Toledano D, Baud FJ: Trends in opiate and opioid poisonings in addicts in north-east Paris and suburbs, 1995–1999. Addiction 2002;97:1295–1304.
  44. Lintzeris N, Mitchell TB, Bond AJ, Nestor L, Strang J: Pharmacodynamics of diazepam co-administered with methadone or buprenorphine under high-dose conditions in opioid-dependent patients. Drug Alcohol Depend 2007;91:187–194.
  45. Chan GM, Stajic M, Marker EK, Hoffman RS, Nelson LS: Testing positive for methadone and either a tricyclic antidepressant or a benzodiazepine is associated with an accidental overdose death: analysis of medical examiner data. Acad Emerg Med 2006;13:543–547.
  46. Mikolaenko I, Robinson CA, Davis GG: A review of methadone deaths in Jefferson County, Alabama. Am J Forensic Med Pathol 2002;29:299–304.

    External Resources

  47. Schifano F, Corkery J, Gilvarry E, Deluca P, Oyefeso A, Ghodse AH: Buprenorphine mortality, seizures and prescription data in the UK, 1980–2002. Hum Psychopharmacol 2005;20:343–348.
  48. Shah N, Lathrop SL, Landen MG: Unintentional methadone-related overdose death in New Mexico (USA) and implications for surveillance, 1998–2002. Addiction 2005;100:176–188.
  49. Martin PR, Arria AM, Fischer G, Kaltenbach K, Heil SH, Stine SM, Coyle MG, Selby P, Jones HE: Psychopharmacologic management of opioid-dependent women during pregnancy. Am J Addict 2009;18:148–156.
  50. Dolovich L, Addis A, Vaillancourt R, Power B, Koren G, Einarson T: Benzodiazepine use in pregnancy and major malformations or oral cleft: meta-analysis of cohort and case-control studies. BMJ 1998;317:839–843.
  51. Seligman N, Salva N, Hayes E, Dysart K, Pequignot E, Baxter J: Predicting length of treatment for neonatal abstinence syndrome in methadone-exposed neonates. Am J Obstet Gynecol 2008;199:396e1–396e7.