Effects of oral clefts on birth outcomes and cleft risks due to maternal smoking

描述(申请人提供)：唇腭裂(CL/P)是一种常见的出生缺陷，具有复杂的意识形态和巨大的健康负担。CL/P对低出生体重和早产等出生结局的影响一直没有得到充分的研究。同样不清楚的是，决定初产结局的因素，如孕妇健康，是否会对未来的发展产生不同的影响，例如，CL/P。另一方面，在以前的几项研究中，母亲吸烟会增加CL/P的风险。然而，这些研究忽略了基于预期怀孕风险和结局的吸烟的潜在自我选择，这可能导致在未考虑吸烟对CL/P风险的影响时存在偏见。这项应用旨在评估单独的CL/P作为一个组以及根据裂隙类型对出生结果的影响，包括低出生体重和早产，并应用分位数回归模型估计有和没有CL/P的婴儿出生体重分位数的差异，以调整几个潜在的混杂因素。初级生育结局的影响决定了产妇的健康和生育史特征，例如，这两个目标将使用拉丁美洲出生缺陷合作研究(ECLAMC)收集的南美出生登记数据，对大约5000例孤立CL/P病例和大约两倍的对照样本进行研究，以进一步了解与CL/P相关的发育差异，并找出简化产前护理和咨询计划的方法，供患有CL/P的怀孕妇女使用。该项目的第三个目标是评估吸烟对CL/P风险的影响，这是通过应用工具变量模型实现的，该模型使用的工具在本项目中是与吸烟有关的遗传方差，但在其他方面与CL/P无关，以利用变异和吸烟，而不是自我选择和混淆。为此，申请者将使用挪威面部裂隙研究招募的大约430例孤立CL/P病例和760名对照样本的环境和遗传数据，这是一项对1996-2001年在挪威出生的大多数CL/P病例进行的人口调查。这些数据还具有强大的优势，包括样本量大，以及感兴趣的吸烟遗传变异已经在这些样本中进行了分类。所提出的工具变量模型提供了一个强大的分析方法，可以扩展到研究母亲吸烟对其他新生儿出生缺陷的影响，如低出生体重和早产。该项目研究了腭裂或分娩结局的影响，目的是确定潜在的方法，以包括受苦妊娠的产前护理计划。另一个目标是对母亲吸烟或唇腭裂风险的影响获得一致的估计。该模型也可应用于其他新生儿疾病的研究。

DESCRIPTION (provided by applicant): Cleft lip and/or palate (CL/P) is a common birth defect with a complex ideology and large health burden. The effects of CL/P on birth outcomes such as low birth weight and prematurity have been understudied. It is also unclear if primary birth outcome determinates such as maternal health might effect future development differently, for instance, with CL/P. On the other hand, maternal smoking has been reported in several previous studies to increase the risk for CL/P. Yet these studies have ignored the potential self selection of smoking based on anticipated pregnancy risks and outcomes which may lead to bias in the effects of smoking on CL/P risks when unaccounted for. This application aims at evaluating the effects of isolated CL/P as one group as well as by cleft type on birth outcomes including low birth weight and prematurity and applies quantile regression models to estimate differences in birth weight quantiles between infants with and without CL/P adjusting for several potential confounders. The effects of primary birth outcome determinates including maternal health and fertility history characteristics, for example, infant sex and the ancestry and prenatal input such as prenatal care will be studied specifically for infants with CL/P and compared to estimates for infants without CL/P to further understand developmental differences related to CL/P and identify approaches to streamline prenatal care and counseling programs available to women with pregnancies that are afflicted with CL/P. These two aims will use South American birth registry data collected by the Collaborative Latin American Study of Birth Defects (ECLAMC) on samples of about 5,000 cases with isolated CL/P and about twice as many controls which is a unique and appropriate data source for these Aims. A third aim of the project is to estimate the effects of smoking on CL/P risk accounting for self selection which is achieved by applying an instrumental variable model that uses instruments which in this project are genetic variance that have been linked to smoking, yet otherwise are unrelated to CL/P to exploit variation and smoking that is free from self selection and confounding. For this aim, the applicants will use environmental and genetic data from about 430 cases with isolated CL/P and 760 control samples recruited to the Norway Facial Cleft Study, a population survey of most CL/P cases that were born in Norway in 1996-2001. These data also have strong advantages including a large sample size and the fact that the smoking genetic variances of interest have already been typed in these samples. A proposed instrumental variable model provides a powerful analytical approach that may be extended to study the effects of maternal smoking on other newborn birth defects such as low birth weight and prematurity. This project studied the effects of cleft with a palate or birth outcomes and aims at identifying potential approaches to include prenatal care programs for afflicted pregnancies. Another aim is to obtain consistent estimates of the effect of maternal smoking or cleft lip and palate risk. The proposed model can be applied to study other newborn disorders.