Tobacco use alters pregnancy biomarkers reflecting tissue function

We have previously identified associations between tobacco exposure and cytokine concentrations in the serum and cervicovaginal fluid. Our aim was to determine the association between urinary cotinine concentration and other biomarkers reflecting tissue level pharmacodynamic changes particularly in placental function and cervical performance. This study was a secondary analysis of a prospective, multi-center study of pregnant women with a singleton gestation and included women with sufficient sample to allow assessment of serum progesterone concentration in the second trimester. Women on progestogen therapy (17-OHPC or vaginal progesterone) were excluded. Concentrations of progesterone and estradiol were measured using an Immulite 1000. Urine cotinine was measured using a validated assay. Analysis of variance was performed to test for associations. Multiple variable regression analysis was used to adjust for potential confounders including age, race, and BMI. 109 women were included at a mean gestational age of 19.9 ± 1.5 weeks. Five patients had previously undergone cervical surgery (LEEP or cerclage) and were excluded from the analyses. Smoking was confirmed by objective measure in 25 of these patients (24%). Rising urinary cotinine values (≥100 ng/mL) were significantly associated with decreasing serum progesterone values, 60 ± 19.5 ng/mL lower cotinine group versus 49 ± 14.6 ng/mL with higher concentrations, P=.024. Serum estradiol was not associated with cotinine values nor was the ratio of serum progesterone/estradiol. The cervical length in the second trimester was also associated with cotinine concentrations. Mean cervical length for smokers was 30 ± 16 mm versus 35 ± 12 mm for nonsmokers, P=.023. The findings remained statistically significant in the adjusted analysis. Urinary cotinine is significantly associated with tissue dysfunction affecting placental production of progesterone and cervical length. Further evaluation of the mechanisms for these findings of tissue dysfunction is needed.