Modifying Progesterone and Estradiol Levels to Prevent Postpartum Cigarette Smoking Relapse and Reduce Secondhand Smoke Exposure in Infants and Children

项目摘要/摘要 产后吸烟复发率十多年来一直停滞不前，其中超过50%的人 哪些人能够在怀孕期间实现戒烟，并在怀孕后头几个月内复发 分娩。母亲吸烟会导致多种不良健康的显著增加 对母亲和孩子都有影响。新生儿和婴儿接触二手烟增加 他们患急性和慢性病的风险。因此，研究确定安全和新颖的产后吸烟 有必要采取预防复发的干预措施。我们的初步数据显示，外源性的 产后早期的黄体酮(Prog)可减少几个与吸烟复发相关的危险因素(例如， 渴望)，也与产后12周戒烟的高流行率有关。 这些观察结果与大量先前的文献一致，这些文献证明了 黄体酮对多种成瘾行为的影响。在我们的另一项初步工作中，我们着眼于非怀孕 绝经前妇女，储存醋酸甲羟孕酮或DMPA，阻止排卵12周 随后会降低雌二醇水平，与之前更长的戒烟尝试有关，并减少 吸烟的动机。这些观察形成了我们的中心假设，即 Prog+DMPA；即增加孕酮和减少雌二醇将防止产后吸烟复发。 为了验证这一假设，我们将进行一项双盲、安慰剂对照、随机临床试验， 将由来自两个地点的经验丰富、跨学科且富有成效的调查团队实施 增强研究样本的多样性和研究结果的普适性。我们将招收健康孕妇 320名最近戒烟并打算产后继续戒烟的妇女。使用2×2阶乘 设计，参与者将被随机分成四个任务之一：(1)Prog+DMPA，(2)Prog+安慰剂，(3) 安慰剂+DMPA，以及(4)安慰剂+安慰剂。参与者将被跟踪数天，直到吸烟复发(主要 结果)、与吸烟有关的危险因素(如渴求)，以及孕期婴儿的健康结果 产后36周至9个月。这项研究提出了一种安全和创新的干预措施来检查 控制产后生理影响新妈妈的行为，这将导致 改善了她和她的婴儿的健康状况。这项新颖的研究的意义将直接推动 通过扩展Prog和DMPA在解决与吸烟有关的问题上的作用来说明科学的现状 在这一高度脆弱的人群中的行为。此外，如果我们的中心假设得到支持， 这种干预措施的临床可译性很高，可能会立即进行。

Project Summary/Abstract Postpartum smoking relapse rates have remained stagnant for over a decade with more than 50% of those who are able to achieve smoking abstinence during pregnancy relapsing within the first few months after childbirth. Maternal cigarette smoking results in significant increases in a variety of negative health consequences for both mother and child. Second-hand smoke exposure to newborns and infants increases their risk of both acute and chronic illness. Therefore, research to identify safe and novel postpartum smoking relapse prevention intervention is warranted. Our preliminary data indicates that the delivery of exogenous progesterone (Prog) in the early postpartum period reduces several smoking relapse related risk factors (e.g., craving) and was also associated with a higher prevalence of smoking abstinence at 12-weeks postpartum. These observations concur with a wealth of prior literature that demonstrates the protective effects of progesterone on a variety of addictive behaviors. In our other preliminary work looking at non-pregnant premenopausal women, depot medroxyprogesterone acetate or DMPA, which blocks ovulation for 12-weeks which subsequently decreases estradiol levels, was associated with longer previous quit attempts and reduced smoking motives. These observations have shaped our central hypothesis which is that the combination of Prog + DMPA; i.e., increased progesterone and decreased estradiol will prevent postpartum smoking relapse. To examine this hypothesis, we will conduct a double-blind, placebo-controlled, randomized clinical trial that will be implemented by an experienced, transdisciplinary, and productive team of investigators from two sites to enhance the diversity of the study sample and generalizability of the results. We will enroll healthy pregnant women (n=320) who have recently quit smoking and intend to stay abstinent postpartum. Using a 2×2 factorial design, participants will be randomized into one of four assignments: (1) Prog + DMPA, (2) Prog + placebo, (3) placebo + DMPA, and (4) placebo + placebo. Participants will be followed for days to smoking relapse (primary outcome), smoking relapse-related risk factors (e.g., craving), and infant health outcomes from gestational week 36 through 9 months postpartum. This study proposes a safe and innovative intervention to examine the impact of manipulating postpartum physiological to influence the behavior of a new mother which will lead to improved health outcomes for her and her infant. The implications of this novel study will directly advance the current state of the science by expanding on the role of Prog and DMPA in addressing smoking-related behaviors within this highly vulnerable population. Further, should our central hypothesis be supported, the clinical translatability of this intervention is high and may be immediately pursued.