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

描述（申请人提供）：唇腭裂（clp）是一种常见的先天缺陷，意识形态复杂，健康负担大。CL/P对低出生体重和早产等出生结局的影响尚未得到充分研究。同样不清楚的是，产妇健康等初生结局决定因素是否会对未来的发展产生不同的影响，例如，CL/P。另一方面，在之前的几项研究中已经报道了母亲吸烟会增加患CL/P的风险。然而，这些研究忽略了基于预期怀孕风险和结果的潜在吸烟自我选择，这可能导致吸烟对CL/P风险影响的偏见，当未被解释时。本应用程序旨在评估孤立的先天性先天性唇裂作为一组以及唇裂类型对出生结局的影响，包括低出生体重和早产，并应用分位数回归模型来估计有和没有先天性先天性唇裂的婴儿出生体重分位数的差异，并调整几个潜在的混杂因素。初产结果的影响决定因素包括产妇健康和生育史特征，例如，婴儿性别、祖先和产前输入，如产前护理，将专门研究患有CL/P的婴儿，并与没有CL/P的婴儿的估计进行比较，以进一步了解与CL/P相关的发育差异，并确定简化产前护理和咨询方案的方法，适用于患有CL/P的怀孕妇女。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，这些数据来自大约5000例孤立性CL/P病例的样本和大约两倍的对照，这是这些目标的独特和适当的数据来源。该项目的第三个目标是估计吸烟对自我选择的CL/P风险的影响，这是通过应用工具变量模型来实现的，该模型使用的工具是与吸烟有关的遗传变异，但在其他方面与CL/P无关，以利用变异和吸烟，没有自我选择和混淆。为了达到这个目的，申请者将使用从挪威面部裂研究中招募的大约430例孤立CL/P病例和760例对照样本的环境和遗传数据，这是一项针对1996-2001年在挪威出生的大多数CL/P病例的人口调查。这些数据也有很强的优势，包括样本量大，而且我们感兴趣的吸烟基因变异已经在这些样本中被键入了。提出的工具变量模型提供了一种强大的分析方法，可以扩展到研究母亲吸烟对其他新生儿缺陷（如低出生体重和早产）的影响。该项目研究了腭裂对出生结果的影响，旨在确定潜在的方法，包括对患病孕妇的产前护理计划。另一个目的是获得对母亲吸烟或唇腭裂风险影响的一致估计。该模型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.