Investigating N-3 Fatty Acids to prevent Neonatal Tobacco-related outcomeS (INFANTS)

项目摘要 吸烟是包括早产在内的不良妊娠结局的最重要的可改变的危险因素， 新生儿死亡和产妇并发症。怀孕期间的吸烟率仍然高得令人无法接受。收费率 妊娠期戒烟率较低，特别是在服务不足的人群中，目前已获批准。 戒烟的药物疗法要么被认为在怀孕期间不安全，要么被认为是不确定的 有效性。确定可减轻吸烟不良影响的安全有效的干预措施 对母婴结局的影响，是一项重大的公共卫生优先事项。我们小组发现吸烟者，两人都怀孕了 和未怀孕的人，在n-3长链多不饱和脂肪酸(LCPUFAs)方面相对不足。我们 假设吸烟引起的n-3 LCPUFA相对缺陷可能是一个重要的机制 导致与烟草相关的不良妊娠结局以及补充n-3LCPUFA 专门针对怀孕吸烟者的可能会减少这些并发症。支持这一假说 来自最近对补充欧米茄-3脂肪酸预防早产的二次分析 分娩试验发现，只有吸烟者服用n-3 LCPUFA才能降低早产风险。 给不吸烟的人。虽然令人信服，但这项研究是一项事后分析，只包括一小部分样本 并且在随访期间没有收集有关吸烟行为的数据。然而，纵向的确定 吸烟行为是至关重要的，因为一些临床研究发现，补充n-3 LCPUFA也可能 减少对尼古丁的渴求，减少日常吸烟。因此，吸烟者可以从补充n-N中获得双重好处。 3 LCPUFA是通过降低早产风险和/或增加戒烟而产生的。要解决这些知识 ，我们正在提议一项n-3 LCPUFA的多中心、随机、安慰剂对照、双盲研究 对400名怀孕吸烟者进行补充。我们将收集有关吸烟行为的详细信息，经过验证 吸烟暴露的生物标志物(尿可替宁、呼气末一氧化碳)和 N-3LCPUFA状态(红细胞膜磷脂膜脂肪酸)。我们这项建议的具体目的是 为了1)确定补充n-3 LCPUFAs对分娩时胎龄和早产的影响 孕妇吸烟者和2)确定补充n-3 LCPUFA对孕妇烟草使用的影响 吸烟者。通过我们最近完成的试点研究，我们优化了我们的招聘和保留 战略，并决定了我们干预的容忍度。我们的研究团队包括经验丰富的 在招募孕妇进行临床研究和执行方面有成功经验的研究人员 戒烟的干预性研究。我们将从八个产科诊所招募潜在参与者。 横跨田纳西州中部地区。这将是对补充n-3个LCPUFA进行的第一次研究 只适用于怀孕的吸烟者。我们的研究可能会对两种有害烟草产生重大的翻译影响- 相关的生育结果和戒烟努力。

Project Summary Smoking is the most important modifiable risk factor for adverse pregnancy outcomes including preterm birth, neonatal death, and maternal complications. Smoking rates in pregnancy remain unacceptably high. Rates of smoking cessation during pregnancy are low, particularly in underserved populations, and currently approved pharmacotherapies for smoking cessation either are considered unsafe in pregnancy or have uncertain effectiveness. Identifying safe and effective interventions, which might mitigate the adverse effects of smoking on maternal-fetal outcomes, is a major public health priority. Our group has found that smokers, both pregnant and non-pregnant, have a relative deficiency in n-3 long-chain polyunsaturated fatty acids (LCPUFAs). We hypothesize that smoking-induced n-3 LCPUFA relative deficiencies may be an important mechanism contributing to tobacco-related adverse pregnancy outcomes and that n-3 LCPUFA supplementation specifically targeted to pregnant smokers may reduce these complications. Support for this hypothesis comes from a recent secondary analysis of the Omega-3 Fatty Acids Supplementation to Prevent Preterm Birth trial that found that only smokers taking n-3 LCPUFAs had a reduction in preterm labor risk as compared to non-smokers. While compelling, this study was a post hoc analysis that included only a small sample of smokers and did not collect data on smoking behaviors during follow up. Yet the ascertainment of longitudinal smoking behavior is critical, as some clinical studies have found that supplemental n-3 LCPUFAs might also reduce nicotine cravings, and lower daily cigarette use. Thus, smokers may doubly benefit from replenishing n- 3 LCPUFAs via lower risk of preterm labor and/or increased smoking cessation. To address these knowledge gaps, we are proposing a multi-center, randomized, placebo-controlled, double-blinded study of n-3 LCPUFA supplementation in 400 pregnant smokers. We will collect detailed information on smoking behavior, validated biological markers of cigarette exposure (urinary cotinine, end-expiratory carbon monoxide) and biomarkers of n-3 LCPUFA status (red blood cell phospholipid membrane fatty acids). Our specific aims of this proposal are to 1) determine the effect of supplemental n-3 LCPUFAs on gestational age at delivery and preterm labor in pregnant smokers and 2) determine the effect of n-3 LCPUFA supplementation on tobacco use in pregnant smokers. Through our recently completed pilot study, we have optimized our recruitment and retention strategies and determined the tolerability of our intervention. Our research team includes experienced researchers with prior successes in recruiting pregnant women for clinical studies and performing interventional studies for smoking cessation. We will recruit potential participants from eight obstetrics clinics across the Middle-Tennessee area. This will be the first study of supplemental n-3 LCPUFAs conducted exclusively in pregnant smokers. Our study could have a major translational impact on both adverse tobacco- related birth outcomes and smoking cessation efforts.