Oral cleft prevention program

口裂预防计划

• 批准号: 7649514
• 负责人: JEFFREY C MURRAY
• 金额: $ 27.46万
• 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/7649514
• 关键词: Accounting; Active Sites; Address; Alcohol consumption; Behavior Therapy; Birth; Birth Weight; Centers for Disease Control and Prevention (U.S.); Child; Cleaved cell; Cleft Lip; Cleft lip with or without cleft palate; Clinical Trials; Cognitive deficits; Communication; Complex; Congenital Abnormality; DNA analysis; Dental; 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; National Institute of Dental and Craniofacial Research; Neural Tube Defects; Neural tube; Operative Surgical Procedures; Outcome; Palate; Parents; Participant; Pharmacologic Substance; Phase; Phenotype; Pre-Eclampsia; Pregnancy; Prevention; Prevention program; Quality Control; Randomized Clinical Trials; Recurrence; Research Ethics Committees; Research Infrastructure; Resources; Risk; Role; Sampling; Serum; Severities; Siblings; Site; Speech; Spontaneous abortion; Supplementation; Syndrome; System; Twin Multiple Birth; United States; Vitamins; Woman; cleft lip and palate; clinical care; data management; design; disorder later incidence prevention; economic cost; experience; folic acid metabolism; high risk; in utero; infant outcome; maternal cigarette smoking; offspring; oral cleft; periconceptual supplementation; 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。它们需要手术、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，其中包括唇裂和/或腭裂、孤立性和非孤立性出生缺陷。对于相关的出生缺陷——神经管缺陷（NTD），有一种有据可查、安全且廉价的预防措施。怀孕前和妊娠前三个月补充叶酸表明，每天补充 4 毫克可将 NTD 复发风险降低约 70%。一些研究还表明叶酸可降低口腔裂复发的风险，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明。进行一项稳健、大规模、双盲、随机临床试验来明确解决这个问题至关重要。在本项目中，我们将完成围孕期补充高剂量叶酸（4 毫克）与低剂量（0.4 毫克）叶酸预防 CLP 复发效果的评估。我们于五年前在 NIDCR、NICHD 和盖茨基金会的赞助下启动了这项研究。本提案旨在利用现有的研究基础设施来完成当前的研究。我们将继续让最好的参与者网站、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 参与数据管理。主要目的是评估每天补充 4 毫克叶酸对减少 CLP 复发的效果，在保守假设下，功效为 0.80，可减少 50%。次要目标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；试验母亲的后代 CLP 的严重程度；流产率和其他出生缺陷率；以及对出生体重和胎龄的影响。在单独的资助下，我们还将研究叶酸代谢相关基因对叶酸、维生素 B12 和同型半胱氨酸水平的作用。该项目解决了一个或多个唇腭裂患者家庭临床护理中的一项基本挑战；即如何管理预防复发。目前，美国每年估计有 1,000 名唇腭裂儿童出生于高风险家庭。如果我们能够将这些家庭的唇腭裂减少 50%，仅在美国，我们就能减轻每个儿童和家庭的个人负担，每年可节省 1 亿美元的唇腭裂相关经济成本。