Massachusetts Center for Birth Defects Research and Prevention

描述(由申请人提供)：MA出生缺陷研究和预防中心(MCBDRP)建议：继续参与国家出生缺陷预防研究并试验新方法；在我们的专门领域进行环境和遗传病因学研究；利用独特的MA妊娠到早期生活纵向数据库对出生缺陷儿童进行跟踪研究；以及试点测试方法，将研究结果转化为预防信息。MA中心将继续在怀孕期间的药物使用和相关风险方面发挥领导作用。作为NBDPS试点项目，MCBDRP将：验证CATI对使用辅助生殖技术的反应；测试评估腹裂在时间和空间上的变化的新方法；评估药物识别手册是否提高了母亲用药反应的可靠性；以及分析早期妊娠血清筛查结果以检验假设 与出生缺陷病因学有关。在第一年，MCBDRP将完成5个病因学研究项目，涵盖医学上重要的和/或常见的风险因素：1)非类固醇抗炎药与出生缺陷风险的关系(非类固醇抗炎药经常被孕妇使用，因此即使是微小的出生缺陷风险增加也可能是重要的，因为潜在受影响的子女的数量很多)；2)血管活性药物和血管破裂缺陷(研究结果将是重要的，因为这些药物很受欢迎，血管破裂的发病机制尚不清楚)；3)治疗妊娠恶心呕吐和先天性心脏病风险的药物(如果用于治疗这种常见疾病的药物导致出生缺陷，则存在相当大的预防机会)；4)血糖负荷和非神经管缺陷(过去几十年来，饮食模式发生了变化，许多人用碳水化合物取代了蛋白质和脂肪的摄入；因此，确定这种高血糖饮食对出生缺陷风险的可能影响至关重要)；和5)新的拷贝数变异和非综合征圆锥干心脏缺陷(这种类型的遗传异常的研究是研究出生缺陷风险因素的一个强有力的新工具，将进一步了解导致这种和其他出生缺陷的胚胎发育机制)。 将在第一年之后继续的其他项目包括一项关于出生缺陷风险的研究，该风险与 含有内分泌干扰物邻苯二甲酸盐的药物。该项目还将作为 评估与药物中非活性成分相关的风险。将对其他相关药物和环境暴露进行流行病学研究，以及对心脏、肢体和横隔膜缺陷的临床描述性研究，MA在这方面拥有特殊的临床专业知识。MCBDRP还将扩大遗传学工作，以：1)识别与其他出生缺陷相关的新拷贝数变异；以及2)识别出生缺陷的药物遗传决定因素。最后，MCBDRP将尽可能利用和评估多种沟通途径，以提高对NBDPS调查结果及其影响的认识。

DESCRIPTION (provided by applicant): The MA Center for Birth Defects Research and Prevention (MCBDRP) proposes to: continue participation in the National Birth Defects Prevention Study and pilot new methods; perform environmental and genetic etiologic research studies in our areas of particular expertise; utilize the unique MA Pregnancy to Early Life Longitudinal database to conduct follow-up research on children with birth defects; and pilot test methods to translate research findings into prevention messages. The MA Center will continue its leadership role on medication use in pregnancy and related risks. As NBDPS pilot projects, the MCBDRP will: validate CATI responses on use of assisted reproductive technology; test novel ways to assess variation in time and space clustering of gastroschisis; assess whether a medication identification booklet improves the reliability of maternal medication responses; and analyze first trimester serum screening results to examine hypotheses related to birth defects etiology. In year one, MCBDRP will complete 5 etiologic research projects that cover medically significant and/or common risk factors: 1) Relation of non-steroidal anti-inflammatory drugs to the risk of birth defects (NSAIDs are frequently used by pregnant women, so even a small increased risk for birth defects could be important because of the number of potentially affected offspring); 2) Vasoactive medications and vascular disruption defects (Findings will be important because these medications are popular and vascular disruption pathogenesis is poorly understood); 3) Drugs for nausea and vomiting of pregnancy and risk of congenital heart defects (If drugs used as a remedy for such a common condition cause birth defects, an opportunity for sizable prevention exists); 4) Glycemic load and non-neural tube defects (Dietary patterns have changed over the past decades, with many persons replacing consumption of proteins and fats with carbohydrates; it is therefore critical to identify the possible impact of such high-glycemic diets on risks of birth defects); and 5) De novo copy number variants and nonsyndromic conotruncal heart defects (Studies of this type of genetic abnormality represents a powerful new tool in studies of risk factors for birth defects that will further understanding of mechanisms of embryologic development that lead to this and other birth defects). Additional projects that will continue beyond year 1 include a study of birth defect risks associated with medications that contain the endocrine-disruptor phthalates. This project will also serve as a model for assessing risk associated with inactive ingredients in medications. Epidemiologic studies of other relevant medication and environmental exposures will be conducted, as will clinical descriptive studies of heart, limb, and diaphragm defects, of which MA has particular clinical expertise. MCBDRP will also expand genetic work to: 1) identify de novo copy number variants associated with other birth defects; and 2) identify pharmacogenetic determinants of birth defects. Finally, the MCBDRP will utilize and evaluate, where possible, multiple communication pathways to raise awareness of NBDPS findings and their implications.