Oral cleft prevention program

口裂预防计划

• 批准号: 7419131
• 负责人: JEFFREY C MURRAY
• 金额: $ 61.8万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-22 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7419131
• 关键词: Accounting; Active Sites; Address; Alcohol consumption; Behavior Therapy; Birth; Caring; Centers for Disease Control and Prevention (U.S.); Child; Cleaved cell; Cleft Lip; Cleft Palate; Clinical; Clinical Trials; Cognitive deficits; Communication; Complex; Condition; Congenital Abnormality; DNA analysis; Dental; Disruption; Dose; Double-Blind Method; Economics; Enrollment; Environmental Exposure; Environmental Risk Factor; Erythrocytes; Etiology; Evaluation; Family; First Pregnancy Trimester; Folate; Folic Acid; Foundations; Funding; Future; Genes; Genotype; Gestational Age; Health; Homocysteine; Homocystine; Human; Impairment; Individual; Intervention; Maintenance; Measures; Medical; Mothers; Multivitamin; National Institute of Child Health and Human Development; Neural Tube Defects; Neural tube; Operative Surgical Procedures; Outcome; Palate; Parents; Participant; Personal Satisfaction; Pharmacologic Substance; Phase; Phenotype; Pre-Eclampsia; Pregnancy; Prevention; Prevention program; Quality Control; Randomized Clinical Trials; Range; Rate; Recurrence; Research Ethics Committees; Research Infrastructure; Resources; Risk; Role; Sampling; Serum; Severities; Siblings; Site; Speech; Spontaneous abortion; Standards of Weights and Measures; Supplementation; Syndrome; System; Twin Multiple Birth; United States; Vitamin, Other; Woman; cleft lip and palate; cost; data management; day; design; disorder later incidence prevention; experience; folic acid metabolism; in utero; infant outcome; maternal cigarette smoking; oral cleft; prevent; psychologic; social

Clefts of the lip and palate (CLP) comprise a large fraction of human birth defects, and are associated with a range of health complications. They require surgical, dental, speech, medical and behavioral interventions and impose a substantial economic and societal burden. CLP is the most prevalent birth defect in the United States, with about 6,800 new cases which includes cleft lip and/or palate, isolated and nonisolated born each year. There is a well documented, safe and inexpensive prevention for a related birth defect - those of the neural tube (NTD). Folic acid supplementation prior to pregnancy and during the first trimester shows that 4 mg per day will decrease NTD recurrence risks by about 70%. A few studies have also suggested decreased risks of recurrence of oral clefts with folic acid but these studies suffer from serious design limitations, and the real effect of folic acid on CLP recurrence remains to be demonstrated. It is critical to conduct a robust, large-scale, double-blinded, randomized clinical trial that clearly addresses this question. In this project we will complete the evaluation of the effect on prevention of CLP recurrence of periconceptual supplementation with high dose folic acid (4 mg) versus low dose (0.4 mg). We initiated this study five years ago under the sponsorship of the NIDCR, NICHD and the Gates Foundation. This proposal is to complete the current study by using the existing research infrastructure. We will continue involvement of the best participant sites, our pharmaceutical partner for inexpensive folate supplements and our experienced clinical trials partner, RTI, for data management. The primary aim is to assess the effect of folic acid supplementation of 4 mg/day on reducing the recurrence of CLP with power of 0.80 to see a 50% reduction under conservative assumptions. Secondary aims include comparing the effects of the two folic acid doses on health outcomes including serum and red cell folate levels; severity of CLP in offspring of trial mothers; rates of miscarriages and other birth defects; and effects on birthweight and gestational age.Under separate funding we will also examine the role of genes involved in folate metabolism on folate, B12 and homocysteine levels. This project addresses a fundamental challenge in the clinical care of families with one or more individuals with a cleft; that is, how to manage recurrence prevention. There are currently an estimated 1,000 births a year of children with clefts coming from high risk families in the US. If we were to realize a 50% reduction in CLP in these families, in the US alone, we would decrease the personal burden on each individual child and family and save $100 million in cleft-related economic costs per year.

嘴唇和pa裂（CLP）占人类出生缺陷的大部分，并且与 一系列健康并发症。他们需要手术，牙科，语音，医学和行为 干预措施并施加实质性的经济和社会负担。 CLP是最普遍的出生 美国的缺陷，大约有6,800例新病例，包括唇裂和/或pape，孤立， 每年非分离出生。有一个有据可查，安全且廉价的预防 出生缺陷 - 神经管（NTD）的缺陷。怀孕前和期间补充叶酸 头三个月表明，每天4毫克将使NTD复发风险降低约70％。一些研究 还表明，叶酸口服裂口复发的风险降低，但这些研究遭受 严重的设计局限性以及叶酸对CLP复发的实际影响尚待证明。 进行健壮，大规模，双盲，随机临床试验至关重要，显然 解决这个问题。在这个项目中，我们将完成对预防CLP影响的评估 高剂量叶酸（4 mg）与低剂量（0.4 mg）的高剂量叶酸（4 mg）的复发性复发。 我们五年前在NIDCR，NICHD和大门的赞助下开始了这项研究 基础。该建议是通过使用现有的研究基础设施来完成当前的研究。 我们将继续参与最佳参与者网站，我们的制药合作伙伴廉价叶酸 补充剂和我们经验丰富的临床试验合作伙伴RTI用于数据管理。 主要目的是评估4 mg/天叶酸补充对减少叶酸的影响 在保守假设下，CLP的复发率为0.80，降低了50％。次要 目的包括比较两种叶酸剂量对血清和红色在内的健康结果的影响 细胞叶酸水平； CLP的严重性在审判母亲的后代；流产和其他先天缺陷的发生率； 以及对出生体重和胎龄的影响。在单独的资金下，我们还将研究 在叶酸，B12和同型半胱氨酸水平上涉及叶酸代谢的基因。 该项目解决了一个或多个家庭的临床护理中的基本挑战 有裂缝的人；也就是说，如何管理预防复发。目前有估计 在美国，每年有1,000名患有裂口的儿童来自高风险家庭。如果我们要意识到 这些家庭中CLP的减少50％，仅在美国，我们就会减轻每个家庭的个人负担 个人儿童和家庭，每年节省1亿美元与裂缝相关的经济成本。