Oral cleft prevention program

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。他们需要外科手术、牙科、语言、医学和行为学 这是一种干预，并造成了巨大的经济和社会负担。中电是最流行的生育方式 在美国，约有6,800例新病例，包括唇裂和/或腭裂，孤立和 每年出生的不是孤立的。有一种有充分记录的、安全和廉价的相关预防措施 出生缺陷-神经管缺陷(NTD)。孕前和孕期补充叶酸 早期妊娠显示，每天服用4毫克可将NTD复发风险降低约70%。几项研究 也表明使用叶酸可降低口腔裂复发的风险，但这些研究受到 严重的设计限制，以及叶酸对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、随机的临床试验是至关重要的， 回答了这个问题。在本项目中，我们将完成对中电预防效果的评估 大剂量叶酸(4 Mg)与小剂量(0.4 mg)叶酸治疗的复发率。 五年前，在NIDCR、NICHD和盖茨的赞助下，我们发起了这项研究 基金会。这项提议是利用现有的研究基础设施来完成目前的研究。 我们将继续参与最好的参与者网站，我们的药物合作伙伴廉价的叶酸 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。 主要目的是评估每天补充4毫克叶酸的效果。 中电以0.80的功率重现，在保守假设下可见减幅达50%。次要的 目的包括比较两种叶酸剂量对健康结果的影响，包括血清和红色 细胞叶酸水平；试验母亲的子代CLP的严重程度；流产和其他出生缺陷的比率； 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 在叶酸、B12和同型半胱氨酸水平上参与叶酸代谢的基因。 该项目解决了临床护理中一个或多个家庭的根本挑战 有裂隙的个人；也就是如何管理复发预防。目前估计有 在美国，每年有1000名患有唇裂的儿童出生于高危家庭。如果我们要实现一个 减少50%的CLP在这些家庭中，仅在美国，我们就会减轻每个家庭的个人负担 每年为每个儿童和家庭节省1亿美元的与唇裂相关的经济成本。

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.