Nicotine Replacement for Smoking Cessation During Pregnancy

描述(由申请人提供)：在美国，30%的低出生体重儿、10%的早产和5%的婴儿死亡是由母亲吸烟造成的。怀孕期间戒烟大大降低了这些风险。不幸的是，即使增加了行为咨询干预，怀孕期间的戒烟率平均也只有13%。戒烟率低可能是由于尼古丁成瘾治疗不当所致。事实上，药物通常被推荐用于非怀孕吸烟者的戒烟治疗；然而，关于帮助孕妇戒烟的药物的安全性和有效性的数据很少。该应用程序响应了NIDA计划的公告(PA 07-329)，以进行研究，以“从母亲和婴儿的健康角度确定在孕妇治疗中使用药物疗法的最佳治疗实践。”该项目将检查尼古丁吸入器作为怀孕期间戒烟辅助工具的安全性和有效性。具体目的是：(1)比较尼古丁吸入器和安慰剂在怀孕期间戒烟和减少吸烟的疗效；(2)比较尼古丁吸入器和安慰剂在尼古丁总暴露(反映在血清可替宁浓度上)和出生结局(即出生体重和胎龄)方面的差异；(3)确定决定哪些妇女在怀孕期间从使用尼古丁吸入器戒烟中受益最大的因素；(4)探讨尼古丁吸入器增加新生儿体重和胎龄的机制。受试者将从主要服务于低收入少数群体的产前诊所招募。每天至少抽五支烟的孕妇吸烟者(n=360)将接受护士提供的行为咨询，并被随机分配接受为期6周的尼古丁吸入器或安慰剂疗程，然后是6周的逐渐减少。所有参与者的分娩结果都将获得。研究人员假设，与安慰剂治疗相比，尼古丁吸入器将导致：1a)7天的戒烟率更高；1b)怀孕32-34周时每天吸烟的人数减少；2a)这两个时间点的可替宁浓度降低；2b)出生体重更高；2c)更长的胎龄和更少的低出生体重和早产；(3)吸烟量较大的人(每天10支)比吸烟量较少的人受益更大；(4)有证据表明，戒烟或减少吸烟解释了出生体重增加，这可能是通过炎症或内皮功能的变化来调节的。这项研究建立在先前工作的基础上，并有望增加对尼古丁吸入器在怀孕期间戒烟的安全性和有效性的了解。

DESCRIPTION (provided by applicant): Maternal smoking is responsible for 30 percent of low birth weight infants, 10 percent of premature deliveries, and 5 percent of all infant deaths in the United States. Smoking cessation during pregnancy substantially reduces these risks. Unfortunately, even with augmented behavioral counseling interventions, the rate of smoking cessation during pregnancy averages only 13 percent. These low quit rates may be due to inadequate treatment of nicotine addiction. Indeed, medications are routinely recommended for smoking cessation treatment in non-pregnant smokers; however, little data are available on the safety and efficacy of medications to help pregnant women quit smoking. This application responds to a NIDA Program Announcement (PA 07-329) for research to "Determine the best treatment practices for the use of pharmacotherapy in the treatment of pregnant women in terms of both mother's and the infant's health." This project will examine the safety and efficacy of the nicotine inhaler as an aid to smoking cessation during pregnancy. The specific aims are: (1) To examine the efficacy of the nicotine inhaler compared to a matching placebo for smoking cessation and reduction during pregnancy; (2) To compare the nicotine inhaler with placebo on overall nicotine exposure (as reflected by serum cotinine concentrations), and on birth outcomes (i.e., birth weight and gestational age); (3) To identify factors that determine which women benefit most from the use of the nicotine inhaler for smoking cessation during pregnancy; (4) To explore mechanisms by which the nicotine inhaler increases birth weight and gestational age. Subjects will be recruited from prenatal clinics that serve primarily a low-income, minority population. Pregnant smokers (n=360) who smoke at least five cigarettes/day will receive nurse-delivered behavioral counseling and be randomized to receive a 6-week course of treatment with either a nicotine inhaler or placebo, followed by a 6-week taper. Birth outcomes will be obtained on all participants. The investigators hypothesize that, compared with placebo treatment, the nicotine inhaler will result in: 1a) higher 7-day point prevalence abstinence rates; 1b) fewer cigarettes smoked per day at 32-34 weeks gestation; 2a) lower cotinine concentrations at these two time points; 2b) higher birth weight infants and 2c) longer gestational age and fewer low-birth-weight and preterm deliveries; (3) greater benefits among heavier smokers (> 10 cigarettes/day) than lighter smokers; (4) evidence that smoking cessation or reduction explains greater birth weight, which may be mediated by changes in markers of inflammation or endothelial function. This study builds on prior work and holds promise for increased understanding of the safety and efficacy of the nicotine inhaler for smoking cessation during pregnancy.