Comparative Safety of commonly prescribed Psychotropic Drugs in pregnant Women

孕妇常用精神药物的比较安全性

• 批准号: 9058606
• 负责人: Sonia Hernandez-Diaz
• 金额: $ 42.19万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9058606
• 关键词: Accounting; Address; Admission activity; Adverse event; Airborne Particulate Matter; Alcohols; Anticonvulsants; Antidepressive Agents; Antiepileptic Agents; Antipsychotic Agents; Anxiety; Attention deficit hyperactivity disorder; Bayesian Method; Benefits and Risks; Benzodiazepines; Bipolar Disorder; Birth; Cesarean section; Characteristics; Conceptions; Confidence Intervals; Databases; Development; Discipline of obstetrics; Dose; Drug usage; Eclampsia; Effectiveness; Epidemiology; Epilepsy; Event; Exposure to; Female of child bearing age; Fetal Growth Retardation; Fetus; Gestational Diabetes; Goals; Growth; Health; Heart Abnormalities; High Prevalence; Hospital Departments; Hospitalization; Incidence; Indigent; Infant; Knowledge; Learning; Low Birth Weight Infant; Medicaid; Medical; Medical Records; Mental disorders; Modeling; Modification; Mood Disorders; Mood stabilizers; Mothers; National Health and Nutrition Examination Survey; Neonatal; Neonatal Abstinence Syndrome; Neurologic; Newborn Infant; Obesity; Outcome; Patients; Pattern; Pharmaceutical Preparations; Physicians; Population; Postpartum Hemorrhage; Pre-Eclampsia; Pregnancy; Pregnant Women; Premature Birth; Psyche structure; Psychotic Disorders; Psychotropic Drugs; Public Health Schools; Recommendation; Records; Relapse; Relative Risks; Research; Risk; Safety; Schizophrenia; Seizures; Smoking; Subgroup; Symptoms; Techniques; Therapeutic; Toxic effect; Withdrawal Symptom; Woman; Work; base; clinical practice; clinically relevant; cohort; comparative; effectiveness clinical trial; evidence based guidelines; experience; fetal; innovation; interdisciplinary collaboration; lamotrigine; malformation; neonatal death; offspring; oral cleft; population based; pregnancy hypertension; pregnant; prenatal exposure; psychostimulant; relapse risk; respiratory; study population; topiramate; trend; unintended pregnancy; valproate; young woman

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.

描述（由申请人提供）：精神疾病使15%以上的怀孕复杂化。其中许多情况需要用精神药物治疗。然而，多项研究表明，产前暴露于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母亲妊娠期糖尿病、先兆子痫和剖宫产的风险增加之间存在关联。另一方面，患有精神和/或神经系统疾病的孕妇停止治疗可能会出现症状复发，这可能对她们及其后代造成危险。由于这些疾病中的许多需要药物治疗，并且许多妊娠是计划外的，因此临床相关问题是：1）建议育龄妇女使用哪种特定药物; 2）妊娠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妊娠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，缺乏知识也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（包括弱势贫困年轻女性）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。我们假设并非所有药物都是平等的，妊娠期间继续治疗的风险-获益权衡因药物而异。我们建议量化与妊娠期间继续和停用特定精神药物相关的母体和胎儿不良事件的风险。在Medicaid Analytic eXtract（MAX）和UnitedHealth Research数据库中，两个基于人口的大型索赔数据库都包含额外的产科，出生和精神病记录，我们将确定2000年至2012年期间分娩的18，500名情绪稳定剂（抗癫痫药），6，500名抗精神病药和3，000名精神兴奋剂的女性。将使用回归模型计算相对风险和95%置信区间，该模型解释了多胎妊娠诱导的可能相关性。我们将采用创新的高维倾向评分技术、工具变量和外部调整的组合，以最大限度地减少混淆的可能性，并采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有关吸烟、酒精和肥胖等潜在混杂因素的信息。目前的建议是布里格姆妇女医院和哈佛公共卫生学院流行病学系之间的跨学科合作。

项目成果

Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations.

• DOI: 10.1001/jamapsychiatry.2016.1520
• 发表时间: 2016-09-01
• 期刊: JAMA psychiatry
• 影响因子: 25.8
• 作者: Huybrechts KF;Hernández-Díaz S;Patorno E;Desai RJ;Mogun H;Dejene SZ;Cohen JM;Panchaud A;Cohen L;Bateman BT
• 通讯作者: Bateman BT

Mortality and Morbidity During Delivery Hospitalization Among Pregnant Women With Epilepsy in the United States.

• DOI: 10.1001/jamaneurol.2015.1017
• 发表时间: 2015-09
• 期刊: JAMA neurology
• 影响因子: 29
• 作者: MacDonald SC;Bateman BT;McElrath TF;Hernández-Díaz S
• 通讯作者: Hernández-Díaz S

Are epidemiological approaches suitable to study risk/preventive factors for human birth defects?

• DOI: 10.1007/s40471-015-0037-5
• 发表时间: 2015-03
• 期刊: Current epidemiology reports
• 影响因子: 3.3
• 作者: Hernandez-Diaz S;Oberg AS
• 通讯作者: Oberg AS

Brief Report: Patterns and Secular Trends in Use of Immunomodulatory Agents During Pregnancy in Women With Rheumatic Conditions.

• DOI: 10.1002/art.39521
• 发表时间: 2016-05
• 期刊: Arthritis & rheumatology (Hoboken, N.J.)
• 作者: Desai RJ;Huybrechts KF;Bateman BT;Hernandez-Diaz S;Mogun H;Gopalakrishnan C;Patorno E;Kim SC
• 通讯作者: Kim SC

Assessment of recording bias in pregnancy studies using health care databases: An application to neurologic conditions.

• DOI: 10.1111/ppe.12459
• 发表时间: 2018-05
• 期刊: Paediatric and perinatal epidemiology
• 影响因子: 2.8
• 作者: MacDonald SC;Hernán MA;McElrath TF;Hernández-Díaz S
• 通讯作者: Hernández-Díaz S