VitC to Decrease Effects of Smoking in Pregnancy on Infant Lung Function-DCC

描述（由申请人提供）： 这是一项双盲、安慰剂对照研究的应用，旨在确定维生素C补充剂（每日500 mg）是否可以降低妊娠期母亲吸烟对后代肺功能（VC-SIP）的影响。怀孕期间吸烟仍然是一个主要的公共卫生问题，因为至少有12%的孕妇在怀孕期间无法戒烟。这种成瘾是儿童呼吸道疾病（包括哮喘）的最大可预防原因，而母亲在怀孕期间吸烟的儿童的肺功能会终生下降。吸烟是一种独特的疾病，因为它是上瘾的，大量的广告和最近的基因组研究表明，有基因型，显着增加无法戒烟的可能性。青少年怀孕，低收入，低教育，和另一个吸烟者一起生活是增加怀孕期间吸烟几率的重要因素。在出生后不久，在怀孕期间吸烟的母亲所生的婴儿进行的肺功能测试显示肺功能下降，通过呼吸流量和顺应性下降以及潮气呼吸模式改变来测量。即使在婴儿成年后，这些变化仍然可以测量。多项流行病学研究表明，这些肺功能的下降导致呼吸系统疾病的增加，每年花费数亿美元。这项多中心研究的主要目的是证明吸烟母亲分娩的婴儿在3个月大时肺功能测试的改善，这些母亲在怀孕22周前随机接受500 mg/天补充维生素C与安慰剂。患者将在每次产前访视时与研究人员会面，并积极鼓励戒烟。将使用一组系列生物标志物监测患者，以评估吸烟和药物依从性，包括尿可替宁水平、吸烟问卷、药丸计数和空腹血浆抗坏血酸水平。肺功能测试将在3个月大时进行，并将测量用力呼气流量。这项研究的成功得到了来自McEhrman博士K23的强有力的初步数据的支持，这些数据显示，接受维生素C的吸烟母亲所生的婴儿的肺功能测试在统计学上显著改善，初步数据显示这些婴儿1岁时喘息的发生率较低。还将测量显示增加对子宫内烟雾暴露的敏感性的关键遗传多态性。这项研究的成功也得到了动物模型的支持，这些动物模型显示了维生素C对保护肺功能的有效性，遗传学和流行病学研究将怀孕期间吸烟的影响与氧化机制联系起来。鉴于尼古丁的成瘾性，患者群体的社会经济性质，以及烟草公司不断的广告，怀孕期间吸烟将继续对全世界数百万婴儿造成不利影响。这项研究具有重大的公共卫生意义，通过阻断子宫内烟雾暴露对肺发育的一些影响，可能改变呼吸系统疾病的胎儿起源。

DESCRIPTION (provided by applicant): This is a application for a double blind, placebo-controlled study to determine if vitamin C supplementation (500 mg daily) can decrease the effect of maternal smoking in pregnancy on offspring pulmonary function (VC-SIP). Smoking during pregnancy remains a major public health problem as at least 12% of pregnant women cannot quit smoking during pregnancy. This addiction is the largest preventable cause of childhood respiratory illness, including asthma, and children whose mothers smoked during pregnancy show lifetime decreases in pulmonary function. Smoking is a unique morbidity in that it is addictive, heavily advertised and recent genome studies show there are genotypes that significantly increase the likelihood of being unable to quit. Teen pregnancy, low income, low education, and living with another smoker are important factors increasing the odds of smoking during pregnancy. Pulmonary function tests done shortly after birth in babies born to mothers who smoked during pregnancy show decreased pulmonary function as measured by decreased respiratory flows and compliance and altered tidal breathing patterns. These changes can still be measured even after the infants have reached adulthood. Multiple epidemiologic studies show that these decreases in pulmonary function lead to increased respiratory disease and costs of hundreds of millions of dollars per year. The primary aim of this multi-site study is to demonstrate improved pulmonary function testing at 3 months of age, in infants delivered to smoking mothers who are randomized to 500 mg/day of supplemental vitamin C versus placebo prior to 22 weeks of pregnancy. Patients will meet with research personnel at each prenatal visit and smoking cessation will be actively encouraged. Patients will be monitored with a set of serial biomarkers to assess smoking and medication compliance, including urine cotinines levels, smoking questionnaires, pill counts and fasting plasma ascorbic acid levels. Pulmonary function tests will be done at 3 months of age and will measure forced expiratory flows. Success of this study is supported by strong pilot data from Dr. McEvoy's K23 showing statistically significant improvements in pulmonary function tests in infants born to smoking mothers who received vitamin C, and preliminary data showing a lower incidence of wheezing at 1 year of age in these infants. Key genetic polymorphisms shown to increase sensitivity to in utero smoke exposure will also be measured. The success of this study is also supported by animal models showing the effectiveness of vitamin C to preserve pulmonary function and genetic and epidemiologic studies linking the effects of smoking during pregnancy to oxidant mechanisms. Given nicotine's addictive nature, the underserved socio-economic nature of the patient population, and the constant advertising by tobacco companies, smoking during pregnancy will continue to adversely victimize millions of babies worldwide. This research has great public health significance to potentially alter the fetal origins of respiratory disease by blocking some of the effects of in-utero smoke exposure on lung development.