Comparative Safety of commonly prescribed Psychotropic Drugs in pregnant Women

描述（由申请人提供）：精神疾病并发症超过所有怀孕的15%。其中许多情况需要用精神药物治疗。然而，多项研究表明，产前接触精神药物与新生儿重大畸形、生长受限、新生儿戒断综合征和呼吸系统问题以及妊娠糖尿病、先兆子痫和母亲剖宫产的风险增加之间存在关联。另一方面，患有精神和/或神经疾病的孕妇如果停止治疗，可能会出现症状复发，这对她们和她们的后代都是危险的。由于许多这些情况需要药物治疗，而且许多怀孕是计划外的，因此临床相关的问题是：1)向育龄妇女推荐哪种特定药物；2)怀孕期间是否以及何时停止治疗。尽管患者和医生面临着困难的决定，但缺乏足够的信息来指导怀孕期间使用精神药物的治疗建议。即使这些药物可能是安全的，但缺乏相关知识可能会给孕妇带来不必要的焦虑。我们的主要目标是提供直接证据，证明用于管理孕妇人群中情绪障碍、精神病和注意缺陷多动障碍（ADHD）的特定策略的相对安全性，其中包括脆弱的贫困年轻女性。我们假设不是所有的药物都是相同的，并且在怀孕期间继续治疗的风险-收益权衡将因药物而异。我们建议量化与妊娠期间持续和停止使用特定精神药物相关的母体和胎儿不良事件的风险。在医疗补助分析提取（MAX）和联合健康研究数据库这两个基于人群的索赔数据库中，我们将确定2000年至2012年间分娩的18,500多名服用情绪稳定剂（抗癫痫药）、6,500名服用抗精神病药和3,000名服用精神兴奋剂的孕妇队列。这两个数据库可链接到额外的产科、分娩和精神病学记录。相对风险和95%置信区间将使用考虑多胎妊娠可能引起的相关性的回归模型来计算。我们将采用高维倾向评分技术、工具变量和外部调整的创新组合，以最大限度地减少混淆的可能性，并使用贝叶斯方法来解释先验信息并支持患者亚组分析。我们将从医疗记录中获取信息，以验证具体结果，并从国家健康和营养检查调查中获取信息，以获取有关吸烟、酒精和肥胖等潜在混杂因素的信息。目前的提案是布里格姆妇女医院和哈佛大学公共卫生学院流行病学部门之间的跨学科合作。

DESCRIPTION (provided by applicant): Mental illnesses complicate over 15% of all pregnancies. Many of these conditions require treatment with psychotropic drugs. However, multiple studies have suggested an association between prenatal exposure to psychotropic drugs and an increased risk of major malformations, growth restriction, neonatal withdrawal syndrome and respiratory problems in the newborn, as well as gestational diabetes, preeclampsia and cesarean section in the mother. On the other hand, pregnant women with mental and/or neurological conditions who discontinue therapy may experience relapse of symptoms that can be dangerous for them and their offspring. Because many of these conditions require pharmacologic treatment and many pregnancies are unplanned, the clinically relevant questions are 1) which specific medication to recommend for women of childbearing age and 2) whether and when to discontinue treatment during pregnancy. Despite the difficult decisions faced by patients and physicians, sufficient information to guide therapeutic recommendations for the use of psychotropic drugs during pregnancy is lacking. Even when these medications may be safe, the lack of knowledge may instill unnecessary anxiety in pregnant women. Our primary objective is to provide direct evidence on the comparative safety of specific strategies used to manage mood disorders, psychosis, and attention deficit hyperactivity disorders (ADHD) in a population of pregnant women, which includes vulnerable indigent young women. We hypothesize that not all drugs are equal and that the risk-benefit trade- off of continuing treatment during pregnancy will differ by drug. We propose to quantify the risk of maternal and fetal adverse events associated with continuing and discontinuing specific psychotropic drugs during pregnancy. Within both the Medicaid Analytic eXtract (MAX) and the UnitedHealth Research database, two large population-based claims databases linkable to additional obstetrical, birth, and psychiatric records, we will identify cohorts of ove 18,500 women on mood stabilizers (antiepileptics), 6,500 on antipsychotics, and 3,000 on psychostimulants at conception who delivered between 2000 and 2012. Relative risks and 95% confidence intervals will be calculated using regression models that account for the possible correlation induced by multiple gestations. We will apply an innovative combination of high dimensional propensity score techniques, instrumental variables and external adjustment to minimize the potential for confounding, and Bayesian approaches to account for prior information and support patient subgroup analyses. We will obtain information from medical records to validate specific outcomes and from the National Health and Nutrition Examination Survey to obtain information on potential confounders such as smoking, alcohol and obesity. The current proposal is an interdisciplinary collaboration between the Brigham and Women's Hospital and the Department of Epidemiology at Harvard School of Public Health.