Oral cleft prevention program

口裂预防计划

• 批准号: 7457784
• 负责人: JEFFREY C MURRAY
• 金额: $ 120.22万
• 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/7457784
• 关键词: Accounting; Active Sites; Address; Alcohol consumption; Behavior Therapy; Birth; Birth Weight; 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

DESCRIPTION (provided by applicant): 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 non-isolated 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 birth weight 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.

描述（由申请人提供）：唇腭裂（CLP）占人类出生缺陷的很大一部分，并与一系列健康并发症相关。它们需要外科、牙科、言语、医疗和行为干预，并造成巨大的经济和社会负担。CLP是美国最常见的出生缺陷，每年约有6,800例新病例，包括孤立性和非孤立性唇腭裂。对于相关的出生缺陷——神经管缺陷（NTD），有一种记录良好、安全且廉价的预防方法。在怀孕前和妊娠早期补充叶酸表明，每天4毫克将使NTD复发风险降低约70%。一些研究也表明，叶酸可以降低唇腭裂复发的风险，但这些研究存在严重的设计局限性，叶酸对CLP复发的真正影响仍有待证实。进行一项强有力的、大规模的、双盲的、随机的临床试验来明确地解决这个问题是至关重要的。在这个项目中，我们将完成对孕期补充高剂量叶酸（4mg）和低剂量叶酸（0.4 mg）对预防CLP复发的效果的评估。我们在五年前开始了这项研究在NIDCR， NICHD和盖茨基金会的赞助下。本提案是利用现有的研究基础设施来完成当前的研究。我们将继续与最佳参与者网站、我们的廉价叶酸补充剂的制药合作伙伴以及我们经验丰富的临床试验合作伙伴RTI合作，进行数据管理。研究的主要目的是评估每天补充4mg叶酸对减少CLP复发的影响，保守假设下，其减少率为0.80，减少率为50%。次要目的包括比较两种叶酸剂量对健康结果的影响，包括血清和红细胞叶酸水平；试验母亲后代CLP的严重程度；流产和其他先天缺陷的比率；以及对出生体重和胎龄的影响。在单独的资助下，我们还将研究与叶酸代谢有关的基因对叶酸、B12和同型半胱氨酸水平的作用。该项目解决了有一个或多个唇裂患者的家庭临床护理中的一个基本挑战；即如何管理复发预防。目前，美国每年约有1000名唇裂患儿出生在高危家庭。如果我们在这些家庭中实现CLP减少50%，仅在美国，我们就可以减轻每个孩子和家庭的个人负担，每年节省1亿美元与唇裂有关的经济成本。