• Bengt Källén


In this chapter, various methodological aspects and the most common sources of information in the literature are briefly discussed. Different methods of ascertainment of congenital malformations and of drug exposure are described, the problem of confounding and of mass significance. A detailed description of the system used when analyzing the Swedish health registers with its positive and negative aspects is given.


  1. Clementi M, Di Gianantonio E, Cassina M, Leoncini E, Botto LD, Mastroiacovo P, Safe-Med Study Group. Treatment of hyperthyroidism in pregnancy and birth defects. J Clin Endocrinol Metab. 2010;95:E337–41.CrossRefGoogle Scholar
  2. Cunnington MC, Well JG, Messerheimer JA, Ferber S, Yerby M, Tennis P. Final results from 18 years of the International Lamotrigine Pregnancy Registry. Neurology. 2011;76:1817–23.CrossRefGoogle Scholar
  3. Czeizel AE. Lack of evidence of teratogenicity of benzodiazepine drugs in Hungary. Reprod Toxicol. 1987–1988;1:183–8.CrossRefGoogle Scholar
  4. Dolk H, Jentink J, Loane M, Morris J, de Jong van den Berg LT, EUROCAT Antieplieptic Drug Working Group. Does lamotrigine use in pregnancy increase orofacial cleft risk relative to other malformations? Neurology. 2008;71:714–22.CrossRefGoogle Scholar
  5. Heinonen OP, Slone D, Shapiro S. Birth defects and drugs in pregnancy. Littleton, MA: Publishing Sciences Group Inc.; 1977.Google Scholar
  6. Holmes LB, Wyszynski DF, Lieberman E. The AED (antiepileptic drug) pregnancy register: a 6-year experience. Arch Neurol. 2004;61:673–8.CrossRefGoogle Scholar
  7. Källén B. A register study of maternal epilepsy and delivery outcome with special reference to drug use. Acta Neurol Scand. 1986;73:253–9.CrossRefGoogle Scholar
  8. Källén B. A prospective study of some aetiological factors in limb reduction defects in Sweden. J Epidemiol Commun Health. 1989;43:86–91.CrossRefGoogle Scholar
  9. Källén B. Drugs during pregnancy. New York: Nova Biomedical Books; 2009.Google Scholar
  10. Källén B. Epidemiology of human congenital malformations. Berlin: Springer; 2014. Scholar
  11. Källén B. Drugs during pregnancy. Methodological aspects. Springer; 2016. Scholar
  12. Källén B, Nilsson E, Otterblad Olausson P. Antidepressant use during pregnancy: comparison of data obtained from a prescription register and from antenatal care records. Eur J Clin Pharmacol. 2011;67:839–45.CrossRefGoogle Scholar
  13. Levy A, Malok I, Gorodischer R, Sherf M, Wiznitzer A, Lisziel E, Koren G. Bias towards the null hypothesis in pregnancy drug studies that do not include data on medical terminations of pregnancy: the folic acid antagonists. J Clin Pharmacol. 2012;52:78–83.CrossRefGoogle Scholar
  14. Magnus P, Irgens LM, Haug K, Nystad W, Skjaerven R, Stoltenberg C. The norwegian mother and child cohort study (MoBa). Int J Epidemiol. 2006;35:1146–50.CrossRefGoogle Scholar
  15. Mitchell AA, Rosenberg L, Shapiro S, Slone D. Birth defects related to bendectin use in pregnancy. JAMA. 1981;245:311–4.CrossRefGoogle Scholar
  16. Olsen J. The danish national birth cohort—the background, structure and aim. Scand J Publ Health. 2001;29:300–7.CrossRefGoogle Scholar
  17. Russell AJC, Craig JJ, Morrison P, Irwin B, Waddell R, Parsons L, Robertson I, Guthrie E, Morrow JI. U.K. epilepsy and pregnancy group. Epilepsia. 2004;45:1467.CrossRefGoogle Scholar
  18. Robert E, Vollset SE, Botto L, Lancaster PA, Merlob P, Mastroiacovo P. Malformation surveillance and maternal drug exposure. Int J Risk Saf Med. 1994;6:75–118.Google Scholar
  19. Stephansson O, Granath F, Svensson T, Haglund B, Ekbom A, Kieler H. Drug use during pregnancy in Sweden—assessed by the prescribed drug register and the medical birth register. Clin Epidemiol. 2011;3:43–50.CrossRefGoogle Scholar
  20. Thomas SV, Jose M, Divarakaran S, Sarma PS. Malformation risk of antiepileptic drug exposure during pregnancy in women with epilepsy: results from a pregnancy registry in South India. Epilepsia. 2017;58(2):274–81. Scholar
  21. Tomson T, Xue H, Battino D. Major congenital malformations in children of women with epilepsy. Seizure. 2015;28:46–50.CrossRefGoogle Scholar
  22. Vajda FJ, Hitchcock A, Graham J, O’Brien T, Lander C, Eadie M. The Australian register of antiepileptic drugs in pregnancy: the first 1002 pregnancies. Aust N Z J Obstet Gynaecol. 2007;47:468–74.CrossRefGoogle Scholar
  23. Wolgast E, Josefsson A, Josefsson M, Liliecreutz C, Reis M. Drug use in pregnant women—a pilot study of the coherence between reported use of drugs and presence of drug in plasma. Eur J Clin Pharmacol. 2018;74:535–9.CrossRefGoogle Scholar
  24. Yoon PW, Rasmussen SA, Lynberg MC, Moore CA, Anderka M, Carmichael SL, Costa P, Druschel C, Hobbs CA, Romitti PA, Langlois PH, Edmonds LD. The national birth defects prevention study. Public Health Rep. 2001;116(Suppl 1):32–40.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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