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

VitC 可减少怀孕期间吸烟对婴儿肺功能的影响-CCC-Lead

• 批准号: 8294342
• 负责人: Cynthia T McEvoy
• 金额: $ 88.04万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-15 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8294342
• 关键词: 1 year old; Adult; Adverse effects; Adverse event; Advertising; Affect; Age-Months; American; Animal Model; Antismoking; Ascorbic Acid; Asthma; Back; Biological Markers; Birth; Breathing; Child; Childhood; Childhood Asthma; Clinical Data; Cost of Illness; Cotinine; Counseling; Data; Dietary Intervention; Disease; Dose; Double-Blind Method; Education; Effectiveness; Enrollment; Epidemiologic Studies; Expenditure; Failure; Fasting; Female; Fetal Growth Retardation; Genetic; Genetic Polymorphism; Genome; Genotype; Health; Healthcare; Hospitalization; Incidence; Infant; Lead; Licensing; Life; Link; Low income; Lung diseases; Measures; Medical; Monitor; Monkeys; Morbidity - disease rate; Mothers; Multi-Institutional Clinical Trial; Nature; Nicotine; Nicotine Dependence; Oxidants; Patients; Pattern; Perinatal mortality demographics; Placebos; Plasma; Pregnancy; Pregnancy in Adolescence; Pregnant Women; Premature Birth; Public Health; Pulmonary function tests; Questionnaires; Randomized; Research; Research Personnel; Respiratory Tract Infections; Respiratory physiology; Risk; Sample Size; Site; Smoke; Smoker; Smoking; Sudden infant death syndrome; Supplementation; Urine; Visit; Wheezing; Woman; Work; abstracting; addiction; base; fetal; fetal tobacco exposure; improved; in utero; interest; lung development; maternal cigarette smoking; medication compliance; meetings; nonhuman primate; offspring; patient population; pill; placebo controlled study; pre-clinical; pregnant; prenatal; prevent; primary outcome; pulmonary function; respiratory; safety study; smoking cessation; socioeconomics; success; tobacco advertising

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. PUBLIC HEALTH RELEVANCE: Maternal smoking during pregnancy is the largest preventable cause of childhood respiratory illness, and children whose mothers smoked during pregnancy show lifetime decreases in pulmonary function and increased respiratory illnesses and asthma. Maternal smoking is estimated to cause 10% of direct medical expenditures in the first year of life and approximately 20% of expenditures for childhood respiratory illness are caused by maternal smoking. The findings from this project will support the addition of a simple, safe, and inexpensive adjunct to current smoking cessation counseling that would significantly decrease the impact of smoking during pregnancy on child respiratory health both in the US and world-wide. (End of Abstract)

描述（由申请人提供）： 这是进行双盲，安慰剂对照研究的应用，以确定补充维生素C（每天500 mg）是否可以降低孕妇在妊娠中吸烟对后代肺功能（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12％的孕妇在怀孕期间无法戒烟。这种成瘾是儿童期呼吸道疾病的最大可预防原因，包括哮喘，以及在怀孕期间吸烟的儿童显示肺功能的寿命降低。吸烟是一种独特的发病率，因为它上瘾，广告广泛，最近的基因组研究表明，基因型大大增加了无法戒烟的可能性。青少年怀孕，低收入，低教育和与另一个吸烟者同住是增加怀孕期间吸烟几率的重要因素。出生后不久，在怀孕期间吸烟的母亲出生后不久进行的肺功能检查显示，肺功能降低，这是通过呼吸道减少和依从性和潮汐呼吸模式改变的肺功能。即使婴儿成年后，这些变化仍然可以衡量。多次流行病学研究表明，肺功能下降会导致呼吸道疾病增加和每年数亿美元的成本。这项多站点研究的主要目的是证明3个月大的肺功能测试改善，在送给吸烟母亲的婴儿中，这些母亲在妊娠22周之前被随机分配至500 mg/天的补充维生素C与安慰剂。患者将在每次产前访问时与研究人员见面，并会积极鼓励戒烟。将使用一组系列生物标志物对患者进行监测，以评估吸烟和药物依从性，包括尿Cotinines水平，吸烟问卷，药丸计数和禁食血浆抗坏血酸水平。肺功能测试将在3个月大时进行，并将测量强迫呼气流。这项研究的成功得到了MCEVOY博士K23的强大试验数据的支持，显示接受维生素C的吸烟母亲出生的婴儿肺功能测试的统计显着改善，并且初步数据表明，这些婴儿在1岁时的喘息发生率较低。还将测量显示出对子宫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，该模型显示了维生素C保留肺功能以及遗传和流行病学研究的有效性，该研究将妊娠期间吸烟与氧化剂机制联系起来。鉴于尼古丁的上瘾性，患者群体服务不足的社会经济性质以及烟草公司不断广告，怀孕期间的吸烟将继续造成全球数百万个婴儿的不利影响。这项研究具有巨大的公共健康意义，可以通过阻止utero烟内暴露对肺部发育的某些影响来改变呼吸道疾病的胎儿起源。 公共卫生相关性： 怀孕期间的孕产妇吸烟是儿童呼吸道疾病的最大可预防原因，而在怀孕期间吸烟的儿童表明肺功能降低了肺部功能，呼吸道疾病和哮喘的增加。据估计，孕产妇吸烟在生命的第一年会导致10％的直接医疗支出，而儿童呼吸道疾病的大约20％是由孕产妇吸烟引起的。该项目的发现将支持当前戒烟咨询的简单，安全和廉价的辅助手段，这将大大降低妊娠期间吸烟对美国和全球儿童呼吸健康健康的影响。 （抽象的结尾）