Date on Master's Thesis/Doctoral Dissertation


Document Type

Doctoral Dissertation

Degree Name

Ph. D.


Epidemiology and Population Health

Degree Program

Public Health Sciences with a specialization in Epidemiology, PhD

Committee Chair

Taylor, Kira

Committee Co-Chair (if applicable)

Baumgartner, Kathy

Committee Member

Baumgartner, Kathy

Committee Member

Wallis, Anne

Committee Member

DuPre, Natalie

Committee Member

Gaskins, Jeremy

Author's Keywords

smoking; secondhand smoke; fertility; fecundability; spontaneous abortion; N-Acetyltransferase 2


Cigarette smoke contains thousands of harmful substances and is one of the leading preventable causes of mortality and morbidity in the United States. Past studies examining tobacco smoke exposures on fecundability and pregnancy outcomes are inconsistent. NAT2 is an important enzyme in the metabolism of xenobiotic substances found within tobacco smoke. This preconception cohort study examines associations between active smoking and secondhand smoke exposure (SHSe) on fecundability and spontaneous abortion (SA), and explores a possible interaction with NAT2 acetylator status. A total of 223 women seeking fertility care were followed for up to 2.3 years. Preconception tobacco smoke exposures were collected by questionnaires and verified by urinary cotinine. SHSe at home and work was measured using the questionnaire (never, rarely (once/week), often (1-6 times/week), daily for each location) and then combined and categorized as low or high SHSe. NAT2 was genotyped to determine acetylator status (rapid vs slow). Pregnancy outcomes (SA vs live birth) were collected on 72 women. Cox proportional hazards regression was used to estimate fecundability ratios (FR) and 95% confidence intervals (CI), and logistic regression to estimate odds ratios (OR) and 95% CIs for the association of active smoking and SHSe on fecundability and SA, respectively. Full models were adjusted for age, BMI, assisted conception, gravidity, marital status, alcohol use and race. Overall, no significant effect of tobacco smoke exposure on fecundability was established. Though statistically insignificant, the effect of smoking on fecundability was stronger among slow NAT2 acetylators. Smokers (OR: 6.28; 95% CI 1.31, 37.9) and nonsmokers with high SHSe (OR: 3.20; 95% CI 0.87, 12.7) had increased odds of SA (ptrend= 0.02), compared to nonsmokers with low SHSe. Among nonsmokers, women with high SHSe had higher odds of SA (OR: 4.30; 95% CI 1.14, 19.1) than women to low SHSe. No significant interaction with NAT2 was reported. Despite wide CIs, results suggest that active smoking and high levels of SHSe may increase in the risk of SA among women seeking fertility care. This dissertation has clinical implications for patient care, and points to biological mechanisms by which tobacco smoke may affect fertility and pregnancy outcomes.