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Maternal Use of Sedatives or Hypnotics and Infant Congenital Malformations

  • Bengt Källén
Chapter

Abstract

Much interest has been paid to the use of sedatives and hypnotics during pregnancy, especially after the finding of the strong teratogenic capacity of thalidomide. The pattern of drug use has changed from barbiturates and meprobamates to benzodiazepines, hypnotic benzodiazepine receptor agonists, and some antihistamines. The literature on benzodiazepines is not consistent but the majority of recent studies have not identified any teratogenic effect. It is possible that some benzodiazepines may be teratogens while others are not. In the Swedish data, alprazolam shows up as a possible teratogen with a main effect on cardiovascular defects but few data on this drug exist in the literature. Other specific benzodiazepines may have a teratogenic effect, not present in the most used drugs, e.g., diazepam or oxazepam. There seems to be little reason to suspect teratogenic effects of hypnotic benzodiazepine receptor agonists or the antihistamine drugs used as sedatives or hypnotics.

References

  1. Ban L, West J, Gibson JE, Flaschi L, Sokal R, Doyle P, Hubbard R, Smeeth L, Tata LJ. First trimester exposure to anxiolytic and hypnotic drugs and the risks of major congenital anomalies: a United Kingdom population-based cohort study. PLoS One. 2014;9:e100996.  https://doi.org/10.1371/journal.pone.0100996.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Bonnot O, Vollset SE, Godet PF, D’Amato T, Robert E. Letter to the editor: maternal exposure to lorazepam and anal atresia in the newborn. Results from a hypothesis-generating study of benzodiazepines and malformations. J Clin Psychopharmacol. 2001;21:456–8.CrossRefGoogle Scholar
  3. Einarson A, Bailey B, Jung G, Spizzirri D, Baillie M, Koren G. Prospective controlled study of hydroxyzine and cetirizine in pregnancy. Ann Allergy Asthma Immunol. 1997;78:183–6.CrossRefGoogle Scholar
  4. Eros E, Czeizel AE, Rockenbauer M, Sørensen HT, Olsen J. A population-based case-control teratologic study of nitrazepam, medazepam, tofisopam, alprazolam and clonazepam treatment during pregnancy. Eur J Obstet Gynecol Reprod Biol. 2002;101:147–54.CrossRefGoogle Scholar
  5. Gidai J, Ács N, Bánhidy F, Czeizel AE. An evaluation of data for 10 children born to mothers who attempted suicide by taking large doses of alprazolam during pregnancy. Toxicol Ind Health. 2008;24:53–60.CrossRefGoogle Scholar
  6. Heinonen OP, Slone D, Shapiro S. Birth defects and drugs in pregnancy. Littleton, MA: Publishing Sciences Group; 1977.Google Scholar
  7. Källén B, Borg N, Reis M. The use of central nervous system active drugs during pregnancy. Pharmaceuticals. 2013;6:1221–86.CrossRefGoogle Scholar
  8. Laegreid L, Olegård R, Conradi N, Hagberg G, Wahlström J, Abrahamsson L. Congenital malformations and maternal consumption of benzodiazepines: a case-control study. Dev Med Child Neurol. 1990;32:432–41.CrossRefGoogle Scholar
  9. Laegreid L, Olegård R, Wahlström J, Conradi N. Teratogenic effects of benzodiazepine use during pregnancy. J Pediatr. 1989;114:126–31.CrossRefGoogle Scholar
  10. Lenz W. Kindlische Missbildungen nach Medikament-Einahme während der Gravidität? Dtsch Med Wochenschr. 1961;86:2555–6.Google Scholar
  11. McBride WG. Thalidomide and congenital abnormalities. Lancet. 1961;278:1358.CrossRefGoogle Scholar
  12. Norstedt Wikner B, Stiller C-O, Bergman U, Asker C, Källén B. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: neonatal outcome and congenital malformations. Pharmacoepidemiol Drug Saf. 2007;16:1203–10.CrossRefGoogle Scholar
  13. Norstedt Wikner B, Källén B. Are hypnotic benzodiazepine receptor agonists teratogenic in humans? J Clin Psychopharmacol. 2011;31:356–8.CrossRefGoogle Scholar
  14. Okun ML, Ebert R, Saini B. A review of sleep-promoting medications use in pregnancy. Am J Obstet Gynecol. 2015;212:428–41.CrossRefGoogle Scholar
  15. Rosenberg L, Mitchell MD, Parsells MS, Pashayan H, Louik C, Shapiro S. Lack of relation between oral clefts and use of diazepam during pregnancy. N Engl J Med. 1983;309:1282–5.CrossRefGoogle Scholar
  16. Safra JM, Oakley GP Jr. Association between cleft lip with or without cleft palate and prenatal exposure to diazepam. Lancet. 1975;2:478–80.CrossRefGoogle Scholar
  17. Saxén I, Saxén L. Letter: association between maternal intake of diazepam and oral clefts. Lancet. 1975;2:498.CrossRefGoogle 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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