Tobacco Center on Regulatory Science, Vermont Center on Behavior and Health, Larner College of Medicine, University of Vermont, Burlington, VT.
Department of Psychological Science, College of Arts and Science, University of Vermont, Burlington, VT.
Nicotine Tob Res. 2019 Nov 19;21(12):1706-1710. doi: 10.1093/ntr/nty172.
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 is unclear. This study investigated how pregnancy alters the nicotine metabolite ratio (NMR), a common biomarker of nicotine metabolism among nonpregnant smokers.
Urinary NMR (trans-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 6 months postpartum (24.7 ± 1.2 weeks since childbirth). Urine samples were analyzed using liquid chromatography-tandem mass spectrometry and NMR were calculated as Total 3HC/Free COT, Free 3HC/Free COT, and Total 3HC/Total COT.
NMR was significantly higher during early and late pregnancy compared to postpartum and significantly increased from early to late pregnancy as 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).
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 as its impact on changes in smoking behavior and cessation outcomes.
We observed that the NMR was significantly higher as early as 12 weeks' gestation and increased further as a function of gestational age. Among nonpregnant smokers, elevated NMR is associated with smoking phenotypes such as smoking more cigarettes per day and poorer response to nicotine patch; therefore, pregnancy-induced increases in the NMR may contribute to smoking during the first trimester of pregnancy and reducing or quitting smoking may become more challenging as the rate of nicotine metabolism accelerates over the course of pregnancy.
怀孕期间尼古丁代谢的增加可能导致孕妇在怀孕期间戒烟困难。然而，目前尚不清楚怀孕期间早期和晚期尼古丁代谢变化的时间过程。本研究旨在探讨妊娠如何改变尼古丁代谢产物比（NMR），这是非孕妇吸烟者中尼古丁代谢的常见生物标志物。
使用液相色谱-串联质谱法分析来自一项随机对照戒烟试验的女性（N=47）的尿液 NMR（反式-3'-羟基可替宁[3HC]/可替宁[COT]），这些女性自我报告吸烟，并在妊娠早期（妊娠 12.5±4.5 周）、妊娠晚期（妊娠 28.9±2.0 周）和产后 6 个月（产后 24.7±1.2 周）提供尿液样本。NMR 计算为总 3HC/游离 COT、游离 3HC/游离 COT 和总 3HC/总 COT。
与产后相比，妊娠早期和晚期的 NMR 显著升高，并且总 3HC/游离 COT（0.76、0.89、0.60；所有 p 值均<.05）和游离 3HC/游离 COT（0.68、0.80、0.51；所有 p 值均<.05）的测量值从妊娠早期到晚期均显著增加。总 3HC/总 COT 随时间无变化（p=0.81）。
妊娠早期总 3HC/游离 COT 和游离 3HC/游离 COT 增加，并在整个妊娠期间持续增加，表明在妊娠期间尼古丁代谢显著增加。需要进一步分析以解释 NMR 变化在尼古丁药代动力学背景下的变化，以及其对吸烟行为和戒烟结果变化的影响。
我们观察到，早在妊娠 12 周时，NMR 就显著升高，并随着胎龄的增加而进一步升高。在非孕妇吸烟者中，NMR 升高与吸烟表型有关，例如每天吸烟更多香烟和对尼古丁贴片的反应较差；因此，随着妊娠期间尼古丁代谢率的加速，妊娠引起的 NMR 增加可能导致妊娠早期吸烟，并随着尼古丁代谢率的加速，减少或戒烟可能变得更加困难。
