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

研究 N-3 脂肪酸以预防新生儿烟草相关后果（婴儿）

• 批准号: 10457304
• 负责人: Harvey J. Murff
• 金额: $ 68.94万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-13 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10457304
• 关键词: Address; Adverse effects; Area; Biochemical; Biological Markers; Birth; Bupropion; Carbon Monoxide; Cigarette; Clinic; Clinical; Clinical Research; Clinical Trials; Cotinine; Data; Discipline of obstetrics; Double-Blind Method; Effectiveness; Enrollment; Erythrocytes; FDA approved; Fatty Acids; Fetal Growth Retardation; Fish Oils; Gestational Age; Intervention; Intervention Studies; Knowledge; Maternal complication; Measures; Mediating; Mediation; Medical Records; Membrane; Neonatal; Nicotine Dependence; Omega-3 Fatty Acids; Outcome; Participant; Patient Recruitments; Patient Self-Report; Pharmacology; Pharmacotherapy; Phospholipids; Pilot Projects; Placebo Control; Placebos; Polyunsaturated Fatty Acids; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Premature Labor; Prenatal care; Public Health; Randomized; Reporting; Research; Research Personnel; Risk; Risk Factors; Sampling; Smoker; Smoking; Smoking Behavior; Southeastern United States; Sudden infant death syndrome; Supplementation; Tennessee; Testing; Tobacco; Tobacco use; Underserved Population; United States; Urine; Woman; adverse pregnancy outcome; care outcomes; cigarette smoking; clinical center; effective intervention; effective therapy; experience; fatty acid supplementation; fetal; follow-up; innovation; modifiable risk; neonatal death; neonatal health; neonatal outcome; nicotine craving; nicotine replacement; non-smoker; novel strategies; placebo controlled study; pregnant; prenatal cigarette smoking; prevent; primary endpoint; public health priorities; public health relevance; recruit; reduce tobacco use; response; retention rate; secondary analysis; secondary endpoint; smoking cessation; smoking during pregnancy; success; tobacco exposure; tobacco use in pregnancy; translational impact; urinary; varenicline

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.

项目概要 吸烟是不良妊娠结局最重要的可改变危险因素，包括早产、 新生儿死亡和孕产妇并发症。怀孕期间的吸烟率仍然高得令人无法接受。费率 怀孕期间戒烟率较低，特别是在服务不足的人群中，目前已批准 戒烟药物疗法被认为在怀孕期间不安全或不确定 效力。确定安全有效的干预措施，可以减轻吸烟的不利影响 母婴结局，是一项重要的公共卫生优先事项。我们小组发现吸烟者，双双怀孕 和非怀孕者，n-3 长链多不饱和脂肪酸 (LCPUFA) 相对缺乏。我们 假设吸烟引起的 n-3 LCPUFA 相对缺乏可能是一个重要机制 n-3 LCPUFA 补充剂会导致与烟草相关的不良妊娠结局 专门针对怀孕吸烟者的可能会减少这些并发症。支持这一假设 来自最近对补充 Omega-3 脂肪酸预防早产的二次分析 出生试验发现，只有吸烟者服用 n-3 LCPUFA 才能降低早产风险 对于非吸烟者。虽然这项研究令人信服，但它是一项事后分析，仅包含一小部分样本 吸烟者并没有在随访期间收集有关吸烟行为的数据。然而纵向的确定 吸烟行为至关重要，因为一些临床研究发现补充 n-3 LCPUFA 也可能 减少对尼古丁的渴望，并减少每日吸烟量。因此，吸烟者可以从补充 n- 中获得双重好处。 3 LCPUFA 可降低早产风险和/或提高戒烟率。针对这些知识点 差距，我们提议对 n-3 LCPUFA 进行多中心、随机、安慰剂对照、双盲研究 400 名怀孕吸烟者的补充剂。我们将收集有关吸烟行为的详细信息，并经过验证 香烟暴露的生物标志物（尿可替宁、呼气末一氧化碳）和 n-3 LCPUFA 状态（红细胞磷脂膜脂肪酸）。我们该提案的具体目标是 1) 确定补充 n-3 LCPUFA 对分娩胎龄和早产的影响 怀孕吸烟者和 2) 确定补充 n-3 LCPUFA 对怀孕吸烟者的影响 吸烟者。通过我们最近完成的试点研究，我们优化了招聘和保留 策略并确定我们干预的耐受性。我们的研究团队包括经验丰富的 先前成功招募孕妇进行临床研究和执行的研究人员 戒烟干预研究。我们将从八家产科诊所招募潜在参与者 横跨田纳西州中部地区。这将是第一项补充 n-3 LCPUFA 的研究 仅适用于怀孕吸烟者。我们的研究可能对不良烟草产生重大转化影响 相关的出生结果和戒烟努力。