Maternal Use of Other Psychoactive Drugs and Infant Congenital Malformations

  • Bengt Källén


The use of methylphenidate for ADHD appears to carry little risk for congenital malformations but more adequate studies are needed. There seems to be little concern about a teratogenic effect of drugs for Parkinsonism, parasymphathomimetic drugs, or drugs for vertigo. Practically no information exists on drugs for dementia or ALS. Nicotine replacement therapy (NRT) may not cause malformations but more data are needed. Other drugs used for smoking cessations have so far not demonstrated teratogenicity. Only little information is available on the use of disulfiram and other drugs for alcohol abuse. Methadone used for opioid addiction may increase the malformation risk while buprenorphine seems to be less risky even though findings vary. Further information is needed but a possible risk must be weighed against the risk of untreated drug abuse.


  1. Alwan S, Reefhuis J, Botto LD, Rasmussen SA, Correa A, Friedman JM, National Birth Defects Prevention Study. Maternal use of bupropion and risk for congenital heart defects. Am J Obstet Gynecol. 2010;203:e1–6. Scholar
  2. Brogly SB, Turner S, Lajkosz K, Davies G, Newman A, Johnson A, Dow K. Infants born of opioid-dependent women in Ontario, 2002–2014. J Obstet Gynaecol Can. 2017;39:157–65.CrossRefGoogle Scholar
  3. Chieza JT, Fleming I, Parry N, Skelton VA. Maternal myasthenia gravis complicated by fetal arthrogryposis multiplex congenitalis. Int J Obstet Anesth. 2011;20:79–82.CrossRefGoogle Scholar
  4. Chun-Fai-Chan B, Korenn G, Favez J, Kaira S, Voyer-Lavigne S, Boshier A, Shakir S, Einarson A. Pregnancy outcome of women exposed to bupropion during pregnancy: a prospective comparative study. Am J Obstet Gynecol. 2005;192:932–6.CrossRefGoogle Scholar
  5. Cleary BJ, Donnelly JM, Strawbridge JD, Gallagher PJ, Fahey T, White MJ, Murphy DJ. Methadone and perinatal outcomes: a retrospective cohort study. Am J Obstet Gynecol. 2011;204:139.e1–9.CrossRefGoogle Scholar
  6. Cole JA, Modell JG, Height BR, Cosmatos IS, Stoler JM, Walker AM. Bupropion in pregnancy and the prevalence of congenital malformations. Pharmacoepidemiol Drug Saf. 2007;16:474–84.CrossRefGoogle Scholar
  7. Coleman T, Cooper S, Thorntorn JG, Grainge MJ, Watts K, Britton J, Lewis S, Smoking, Nicotine, and Pregnancy (SNAP) Trial Team. A randomized trial of nicotine-replacement therapy patches in pregnancy. N Engl J Med. 2012;366:808–18.CrossRefGoogle Scholar
  8. Dhalwani NN, Szatkowski L, Coleman T, Fiaschi L, Tata LJ. Nicotine replacement therapy in pregnancy and major congenital anomalies in offspring. Pediatrics. 2015;135:859–67.CrossRefGoogle Scholar
  9. Diav-Citrin O, Schechtman S, Arnon J, Weinberg R, Borisch C, Beck E, Richardson JL, Bozzo P, Nulman J, Ornoy A. Methylphenidate in pregnancy: a multicenter, prospective, comparative, observational study. J Clin Psychiatry. 2016;77:1176–81.CrossRefGoogle Scholar
  10. Dideriksen D, Pottegård A, Hallas J, Aagaard L, Damkler P. First trimester in utero exposure to methylphenidate. Basic Clin Pharmacol Toxicol. 2013;112:73–6.CrossRefGoogle Scholar
  11. Dinger J, Prager B. Arthrogryposis multiplex in a newborn of a myasthenic mother—case report and literature. Neuromuscul Disord. 1993;3:335–9.CrossRefGoogle Scholar
  12. Dostal M, Webet-Schoendorfer C, Sobesky J, Schaefer C. Pregnancy outcome following use of levodopa, pramipexole, ropinirole, and rotigotine for restless legs syndrome during pregnancy: a case series. Eur J Neurol. 2013;20:1241–6.CrossRefGoogle Scholar
  13. Glaxo/SmithKline. The bupropion pregnancy registry. Final report. 2008.
  14. Harrison-Woolrych M, Paterson H, Tan M. Exposure to the smoking cessation medicine varenicline during pregnancy: a prospective nationwide cohort study. Pharmacoepidemiol Drug Saf. 2013;2013(22):1086–92.Google Scholar
  15. Heinonen OP, Slone D, Shapiro S. Birth defects and drugs in pregnancy. Littleton, MA: Publishing Sciences Group; 1977.Google Scholar
  16. Huybrechts KF, Palmgren K, Avorri J, Cohen LS, Holmes LB, Franklin JM, Mogun H, Levin R, Kowal M, Seroguchi S, Hernández-Diaz S. Antidepressant use in pregnancy and the risk of cardiac defects. N Engl J Med. 2014;370:2397–407.CrossRefGoogle Scholar
  17. Hyubrechts KF, Bröms G, Christensen LB, Einarsdotter K, Engeland A, Furu K, Gissler M, Hernandez-Diaz S, Karlsson P, Karlstad Ø, Kieler H, Lahesmaa-Korpinen AM, Mogun H, Nørgaard M, Reutfors J, Sørensen HT, Zoega H, Baterman BT. Association between methylphenidate and amphetamine use in pregnancy and risk of congenital malformations: a cohort study from the International Pregnancy Safety Study Consortium. JAMA Psychiat. 2018;75:167–75.CrossRefGoogle Scholar
  18. Källén B, Borg N, Reis M. The use of central nervous system active drugs during pregnancy. Pharmaceuticals. 2013;6:1221–86.CrossRefGoogle Scholar
  19. Kelty E, Hulse G. A retrospective cohort study of birth outcomes in neonates exposed to naltrexone in utero: a comparison with methadone-, buprenorphine- and non-opioid exposed neonates. Drugs. 2017;77:1211–9.CrossRefGoogle Scholar
  20. Lacroix I, Berrebi A, Chaumerliac C, Lapeyre-Mestro M, Montastruc JL, Damase-Michel C. Buprenorphine in pregnant opioid-dependent women: a prospective multicenter study. Eur J Clin Pharmacol. 2011;67:1053–9.CrossRefGoogle Scholar
  21. Litta R, Rainone R, Zingaviello L. A case of incomplete amelia. Pediatria (Napoli). 1983;91:287–93.Google Scholar
  22. Luik C, Kerr S, Mitchell AA. First trimester exposure to bupropion and risk of cardiac malformations. Pharmacoepidemiol Drug Saf. 2014;23:1066–75.CrossRefGoogle Scholar
  23. Morales-Suárez-Varela MM, Bile C, Christensen K, Olsen J. Smoking habits, nicotine use, and congenital malformations. Obstet Gynecol. 2006;107:51–7.CrossRefGoogle Scholar
  24. Niesen CE, Shah NS. Pyridostigmine-induced microcephaly. Neurology. 2000;54:1873–4.CrossRefGoogle Scholar
  25. Nora JJ, Nora AH, Way GL. Cardiovascular maldevelopment associated with maternal exposure to amantadine. Lancet. 1975;2:607.CrossRefGoogle Scholar
  26. Nörby U, Winbladh B, Källén K. Perinatal outcome after treatment with ADHD medication during pregnancy. Pediatrics. 2017;140:e20170747. Scholar
  27. Nørgaard M, Nielsson MS, Heide-Jørgensen U. Birth and neonatal outcomes following opioid use in pregnancy: a Danish population-based study. Subst Abus. 2015;9:5–11.Google Scholar
  28. Pandit PB, Chilavat D, Jefferies AL, Landes A, Quamar IU, Koren G. Tibial hemimelia and tetralogy of Fallot associated with first trimester exposure to amantadine. Reprod Toxicol. 1994;8:89–92.CrossRefGoogle Scholar
  29. Pottegård A, Hallas J, Andersen JT, Løkkegaard EC, Dideriksen D, Aagaard L, Damkier P. First-trimester exposure to methylphenidate: a population-based cohort study. J Clin Psychiatry. 2014;75:e88–93. Scholar
  30. Richardson JL, Stephens S, Yates LM, Diav-Citrin O, Amon J, Beghin O, Kayser A, Kennedy D, Cupitt D, Te Winkel B, Peltonen M, Kaplan YC, Thomas SH. Pregnancy outcomes after maternal varenicline use: analysis of surveillance data collected by the European Network of Teratology Information Services. Reprod Toxicol. 2017;67:26–34.CrossRefGoogle Scholar
  31. Wickström R. Effects of nicotine during pregnancy: human and experimental evidence. Curr Neuropharmacol. 2007;5:213–32.CrossRefGoogle Scholar
  32. Wurst KE, Zedler BK, Joyce AR, Sasinowski M, Murrelle EL. A Swedish population-based study of adverse birth outcomes among pregnant women treated with buprenorphine or methadone: preliminary findings. Subst Abus. 2016;10:89–97.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Bengt Källén
    • 1
  1. 1.Tornblad Institute for Comparative EmbryologyLund UniversityLundSweden

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