Nicotine Replacement for Smoking Cessation During Pregnancy

描述（由申请人提供）：在美国，母亲吸烟导致30%的低出生体重婴儿，10%的早产和5%的婴儿死亡。怀孕期间戒烟可以大大降低这些风险。不幸的是，即使加强了行为咨询干预，怀孕期间的戒烟率平均只有13%。这些低戒烟率可能是由于尼古丁成瘾治疗不足。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。本申请是对NIDA计划公告（PA 07-329）的回应，该公告的研究目的是“确定在母亲和婴儿健康方面使用药物治疗孕妇的最佳治疗实践”。“这项计划将研究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。具体目标是：（1）检查尼古丁吸入器与匹配的安慰剂相比在妊娠期间戒烟和减少吸烟的有效性;（2）比较尼古丁吸入器与安慰剂在总体尼古丁暴露（如血清可替宁浓度所反映的）和出生结局（即，出生体重和胎龄）;（3）确定哪些妇女在妊娠期间使用尼古丁吸入器戒烟获益最大的因素;（4）探索尼古丁吸入器增加出生体重和胎龄的机制。受试者将从主要为低收入少数民族人口服务的产前诊所招募。每天吸烟至少5支的妊娠吸烟者（n=360）将接受护士提供的行为咨询，并随机接受尼古丁吸入器或安慰剂的6周疗程，随后进行6周的减量。将获得所有受试者的出生结局。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天时点戒烟率较高; 1b）妊娠32-34周每天吸烟量较少; 2a）这两个时间点的可替宁浓度较低; 2b）出生体重较高的婴儿和2c）胎龄较长，低出生体重和早产较少;（3）重度吸烟者（> 10支/天）比轻度吸烟者的益处更大;（4）有证据表明，戒烟或减少吸烟可以解释出生体重增加，这可能是由炎症或内皮功能标志物的变化介导的。这项研究建立在以前的工作基础上，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.