Fetal exposure to maternal cigarette smoking and male reproductive function in young adulthood

Katia Keglberg Hærvig, Kajsa Ugelvig Petersen, Aleksander Giwercman, Karin Sørig Hougaard, Birgit Bjerre Høyer, Christian Lindh, Cecilia Høst Ramlau-Hansen, Anne Marie Nybo Andersen, Gunnar Toft, Jens Peter Bonde, Sandra Søgaard Tøttenborg

Research output: Contribution to journalArticlepeer-review


Maternal smoking during pregnancy constitutes a potential, major risk factor for adult male reproductive function. In the hitherto largest longitudinal cohort, we examined biomarkers of reproductive function according to maternal smoking during the first trimester and investigated whether associations were mitigated by smoking cessation prior to the fetal masculinization programming window. Associations between exposure to maternal smoking and semen characteristics, testicular volume and reproductive hormones were assessed among 984 young men from the Fetal Programming of Semen Quality (FEPOS) cohort. Maternal smoking was assessed through interview data and measured plasma cotinine levels during pregnancy. We applied negative binomial, logistic and linear regression models to estimate differences in outcomes according to levels of maternal smoking. Sons of light smokers (≤ 10 cigarettes/day) had a 19% (95% CI − 29%, − 6%) lower sperm concentration and a 24% (95% CI − 35%, − 11%) lower total sperm count than sons of non-smokers. These estimates were 38% (95% CI − 52%, − 22%) and 33% (95% CI − 51%, − 8%), respectively, for sons of heavy smokers (> 10 cigarettes/day). The latter group also had a 25% (95% CI 1%, 54%) higher follitropin level. Similarly, sons exposed to maternal cotinine levels of > 10 ng/mL had lower sperm concentration and total sperm count. Smoking cessation prior to gestational week seven was not associated with a higher reproductive capacity. We observed substantial and consistent exposure–response associations, providing strong support for the hypothesis that maternal smoking impairs male reproductive function. This association persisted regardless of smoking cessation in early pregnancy.

Original languageEnglish
Pages (from-to)525-538
Number of pages14
JournalEuropean Journal of Epidemiology
Issue number5
Publication statusPublished - 2022

Subject classification (UKÄ)

  • Environmental Health and Occupational Health
  • Obstetrics, Gynecology and Reproductive Medicine

Free keywords

  • Fetal programming
  • Male infertility
  • Maternal smoking
  • Prenatal exposure
  • Reproductive hormones
  • Semen quality


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