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Pregnancy-Induced Increases in the Nicotine Metabolite Ratio: Examining Changes During Antepartum and Postpartum.

Introduction
Pregnancy-induced increases in nicotine metabolism may contribute to difficulties in quitting smoking during pregnancy. However, the time-course of changes in nicotine metabolism during early and late pregnancy are unclear. The present study investigated how pregnancy alters the nicotine metabolite ratio (NMR), a common biomarker of nicotine metabolism among non-pregnant smokers.


Methods
Urinary NMR (3-hydroxycotinine (3HC)/cotinine (COT)) was assessed using total (free + glucuronide) and free compounds among women (N=47) from a randomized controlled trial for smoking cessation who self-reported smoking and provided a urine sample during early pregnancy (M ± SD = 12.5 ± 4.5 weeks gestation), late pregnancy (28.9 ± 2.0 weeks gestation) and six months postpartum (24.7 ± 1.2 weeks since childbirth). Urine samples were analyzed using LC-MS/MS and NMR was calculated as Total 3HC/Free COT, Free 3HC/Free COT, and Total 3HC/Total COT.


Results
NMR was significantly higher during early and late pregnancy compared to postpartum and significantly increased from early to late pregnancy measured by Total 3HC/Free COT (0.76, 0.89, 0.60; all p's < .05) and Free 3HC/Free COT (0.68, 0.80, 0.51; all p's < .05). Total 3HC/Total COT did not vary over time (p = .81).


Conclusions
Total 3HC/Free COT and Free 3HC/Free COT increased in the first trimester and continued to increase throughout pregnancy suggesting a considerable increase in nicotine metabolism over gestation. Future analyses are needed to interpret the changes in NMR in the context of nicotine pharmacokinetics, as well its impact on changes in smoking behavior and cessation outcomes.