Massachusetts Center for Birth Defects Research and Prevention

描述（由申请人提供）：马萨诸塞州（MA）出生缺陷研究和预防中心（MCBDRP）提议通过参与出生缺陷研究以评估妊娠暴露（BD-STEPS），继续其进行病因学研究以确定结构性出生缺陷的可改变风险因素的良好记录。我们将通过利用我们已经建立的培训计划来加强我们的贡献，该计划旨在培养未来的出生缺陷研究人员。MCBDRP为BD-STEPS带来了我们在药物流行病学和独特数据资源协作利用方面的专业知识和领导，这些资源将应用于资助机会公告中提到的所有四个关键领域。我们的研究将利用来自国家出生缺陷预防研究的现有数据，作为BD-STEPS的一部分收集的数据，以及我们合作团队独有的数据集，包括妊娠至早期生命纵向数据库，辅助生殖技术的MA结果研究，斯隆流行病学中心的多站点出生缺陷研究和北美抗癫痫药物妊娠登记。MCBDRP研究人员是忠诚和成功的导师和合作伙伴，他们的角色将在BD-STEPS中继续扩大。在五年的资助期内，MCBDRP将完成至少10个病因学研究项目，涵盖与出生缺陷风险相关的医学上重要和常见的暴露，包括：1)口服糖尿病药物，随着糖尿病患病率的增加而更加常见；2)抗肥胖药物，鉴于目前肥胖的增加已经并将继续得到FDA的批准；3)治疗不孕症的药物和程序，由于大量高龄母亲和辅助生殖技术（ART）的高利用率，MA在这一领域具有独特的优势；4)含有内分泌干扰物邻苯二甲酸盐的药物，这将成为建议研究药物中其他非活性成分的模型；5)抗癫痫药物，包括增加出生缺陷风险的遗传因素的研究；6)非甾体类抗炎药，这很重要，因为超过20%的孕妇在使用它们；7)妊娠期恶心和呕吐的药物，关键是由于某些药物用于这种妊娠特异性疾病的使用越来越多；8)出生缺陷的时空聚类，这是环境或感染病因的指示，包括扩大我们在腹裂上的工作，并将研究方法扩展到其他出生缺陷；9)抗抑郁药，特别是选择性血清素再摄取抑制剂，包括与特定药物相关的效果调节剂和基因决定的预测因子；10)怀孕期间服用的药物，包括非处方药，并通过定期筛查BD-STEPS数据，确定可能构成风险的新产品。通过这些活动，MCBDRP将成为BD-STEPS的重要伙伴，以实现我们将研究成果转化为有意义的预防举措的总体目标。

DESCRIPTION (provided by applicant): The Massachusetts (MA) Center for Birth Defects Research and Prevention (MCBDRP) proposes to continue its strong track record of conducting etiologic research to identify modifiable risk factors for structural birth defects through its participation in the Birth Defects Study to Evaluate Pregnancy exposureS (BD-STEPS). We will enhance our contributions by leveraging our already established training program designed to produce future birth defects researchers. MCBDRP brings to BD-STEPS our expertise and leadership in pharmacoepidemiology and collaborative utilization of unique data resources to be applied to all four key areas named in the Funding Opportunity Announcement. Our research will utilize existing data from the National Birth Defects Prevention Study, data to be collected a part of BD-STEPS and data sets unique to our collaborative team including the Pregnancy to Early Life Longitudinal database, the MA Outcomes Study of Assisted Reproductive Technologies, the Slone Epidemiology Center's multi-site Birth Defects Study, and the North American Antiepileptic Drug Pregnancy Registry. MCBDRP investigators are committed and successful mentors and collaborative partners, roles that will continue and expand within BD-STEPS. Over the five year grant period, the MCBDRP will complete at least 10 etiologic research projects that cover medically significant and common exposures as they relate to risks of birth defects including: 1) Oral diabetic medications, more common as the prevalence of diabetes increases; 2) Anti-obesity medications, which given the current increase in obesity have been and will continue to be approved by FDA; 3) Medications and procedures to treat infertility, an area where MA offers unique strengths due to the large number of older mothers and high utilization of assisted reproductive technology (ART); 4) Medications that contain the endocrine-disruptor phthalates, which will be a model for proposing to study additional inactive ingredients in medications; 5) Antiepileptic medications including the study of genetic factors which increase the risk for birth defects; 6) Non- steroidal anti-inflammatory drugs, important because they are used by more than 20% of pregnant women; 7) Drugs for nausea and vomiting of pregnancy, key because of the increasing use of some medications for this pregnancy-specific condition; 8) Spatio-temporal clustering of birth defects, an indication of environmental or infectious etiology, including an expansion of our work on gastroschisis and extension of the research methodology to other birth defects; 9) Antidepressants, specifically selective serotonin reuptake inhibitors, including effect modifiers and genetically determined predictors related to specific agents; and 10) Medications taken during pregnancy, including over-the-counter products, and through a periodic screening of BD-STEPS data, identifying new products that may pose a risk. Through these activities, MCBDRP will be an essential partner in BD-STEPS to achieve our overall goal of translating research findings into meaningful prevention initiatives.