The Nicotine Metabolite Ratio in Pregnancy Measured by trans-3′-Hydroxycotinine to Cotinine Ratio: Characteristics and Relationship With Smoking Cessation

Nicotine replacement therapy (NRT) helps nonpregnant smokers quit, but there is no evidence that standard dose NRT is effective in pregnancy. As nicotine metabolism increases in pregnancy, this could reduce NRT efficacy. Using the ratio of trans-3'-hydroxycotinine to cotinine, the nicotine metabolite ratio (NMR), we investigated relationships between the rate of nicotine metabolism, maternal characteristics and smoking cessation in pregnant women recruited to a randomized controlled trial of NRT. Data from 1,050 pregnant smokers in the Smoking, Nicotine and Pregnancy trial who were of 12-24 weeks gestation had exhaled carbon monoxide readings of a parts per thousand yen8 ppm at recruitment and who were randomized to NRT or placebo patches were used. Linear and logistic regression investigated associations between maternal characteristics and NMR and also between NMR and subsequent validated cessation from smoking. Six hundred and sixty-two women (63%) provided blood samples for NMR estimation. Higher NMR was associated with increased cigarette consumption prior to pregnancy. At 1 month (odds ratio [OR] = 0.87; 95% CI = 0.76-0.99; p = .043) and delivery (OR = 0.79; 95% CI = 0.66-0.95; p = .010), there was a significant negative association between a 0.1 unit increase in NMR and odds of achieving cessation after adjusting for possible confounders. There was no evidence for an interaction between a 0.1 unit increase in NMR and treatment assignment on the odds of cessation at 1 month post-quit date (p = .556). Pregnant women who metabolize nicotine more rapidly are less likely to achieve cessation when they try to quit smoking. There is no evidence that NRT is more effective in women who metabolize nicotine more slowly.