Metamizole use during first trimester-A prospective observational cohort study on pregnancy outcome

Pharmacoepidemiol Drug Saf. 2017 Oct;26(10):1197-1204. doi: 10.1002/pds.4277. Epub 2017 Aug 3.


Introduction: The analgesic metamizole (dipyrone) is not recommended during pregnancy due to limited experience. In several countries, metamizole has no market authorization because of agranulocytosis as a rare but severe adverse effect. However, in others, metamizole is available and widely used as a pain reliever, and its use occurs also during pregnancy, often followed by fears of potential teratogenic risk.

Methods: This prospective observational cohort study compared pregnancy outcomes of 446 women exposed with metamizole in the first trimester with a randomly selected control cohort comprising 887 women not exposed to metamizole. Relevant data were obtained via structured questionnaires applied during the first trimester and 2 months after the expected date of birth between January 2000 and December 2015.

Results: The rate of major birth defects (7/373, 1.9%) was not increased in the metamizole cohort (OR adjusted 1.15, 95% CI 0.4-3.5). The cumulative incidences for spontaneous abortions did not reveal a significant difference between the exposed (12.2%, 32/446) and comparison cohort (19.4%, 77/887) (HR adjusted 0.72, 95% CI 0.5-1.1). Elective terminations of pregnancy (ETOP), mostly for "social" reasons, were more frequent in the metamizole (12.5%, 45/446) than in the comparison cohort (9.4%, 50/887; HR adjusted 1.48, 95% CI 0.98-2.2).

Conclusions: Metamizole exposure in the first trimester does not seem to bear a substantial teratogenic risk. Our study results support reassurance in those instances where metamizole has been used during an unrecognized pregnancy or where its use appears indispensable.

Keywords: analgesic; birth defects; metamizole; pharmacoepidemiology; pregnancy outcome.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Abnormalities, Drug-Induced / epidemiology*
  • Abortion, Induced / statistics & numerical data
  • Adolescent
  • Adult
  • Analgesics / adverse effects*
  • Dipyrone / adverse effects*
  • Female
  • Humans
  • Incidence
  • Middle Aged
  • Pain / drug therapy*
  • Pain Management / adverse effects*
  • Pain Management / methods
  • Pharmacovigilance
  • Pregnancy
  • Pregnancy Outcome / epidemiology*
  • Pregnancy Trimester, First / drug effects*
  • Premature Birth / epidemiology
  • Prospective Studies
  • Risk Factors
  • Surveys and Questionnaires
  • Teratogenesis / drug effects
  • Young Adult


  • Analgesics
  • Dipyrone