Risk of adverse birth outcomes after maternal varenicline use: A population-based observational study in Denmark and Sweden

Pharmacoepidemiol Drug Saf. 2020 Jan;29(1):94-102. doi: 10.1002/pds.4894. Epub 2019 Nov 11.


Purpose: To examine risks of adverse birth outcomes in women exposed to varenicline during pregnancy.

Methods: Population-based cohort study including live-born and stillborn infants from 1 May 2007 to 31 December 2012. Data from health and administrative registries in Denmark and Sweden, two Nordic countries with universal health care and routine registration of major life and health events. Infants were allocated to three cohorts on the basis of their in utero exposure: the exposed cohort consisting of infants whose mothers were dispensed varenicline during pregnancy; the unexposed cohort comprised infants unexposed to varenicline, but exposed to maternal smoking in utero; and the reference cohort of infants unexposed to varenicline and maternal smoking in utero. The primary outcome was major congenital malformations diagnosed from birth to the first year of life. Secondary outcomes included stillbirth, fetal growth restriction (measured as small for gestational age), preterm delivery, preterm premature rupture of membranes, and sudden infant death syndrome. We estimated the prevalence of the primary outcome and secondary outcomes in the exposed, unexposed, and reference cohorts. Prevalence odds ratios with 95% confidence intervals (CIs) were computed using logistic regression with propensity score adjustment to control for potential confounders.

Results: The combined cohort included 885 185 infants. Of these, 335 infants were exposed, 78 412 were unexposed, and the remaining 806 438 comprised the reference cohort. Major congenital malformations were detected among 3.6% of exposed infants, 4.3% of unexposed infants, and 4.2% of infants in the reference cohort. The propensity score-adjusted prevalence odds ratio for major congenital malformations was 0.80 (95% CI, 0.45-1.42) for exposed vs unexposed infants. All analyses of primary and secondary outcomes comparing exposed with unexposed infants yielded odds ratio estimates below or close to unity. Use of varenicline during pregnancy does not appear to increase the risk of major congenital malformations or other adverse birth outcomes.

Keywords: observational study; pharmacoepidemiology; pregnancy outcome; varenicline.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / epidemiology*
  • Adult
  • Adverse Drug Reaction Reporting Systems
  • Denmark / epidemiology
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Maternal Exposure / adverse effects*
  • Middle Aged
  • Pharmacoepidemiology
  • Pregnancy
  • Prenatal Care*
  • Registries
  • Smoking Cessation Agents / adverse effects*
  • Smoking*
  • Stillbirth / epidemiology*
  • Sweden / epidemiology
  • Varenicline / adverse effects*
  • Young Adult


  • Smoking Cessation Agents
  • Varenicline