Safety of Benzodiazepines and Non-Benzodiazepine Sedative Hypnotics in Pregnancy

妊娠期苯二氮卓类药物和非苯二氮卓类镇静催眠药的安全性

• 批准号: 10672462
• 负责人: Brian Thomas Bateman
• 金额: $ 62.04万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10672462
• 关键词: Address; Admission activity; American College of Obstetricians and Gynecologists; Anatomy; Anxiety Disorders; Benefits and Risks; Benzodiazepines; Central Nervous System; Child; Confounding Factors (Epidemiology); Congenital Abnormality; Data; Data Sources; Databases; Discipline of obstetrics; Disease; Dose; Etiology; Fetal Development; Fetal Growth; Fetus; First Pregnancy Trimester; Generalized Anxiety Disorder; Generations; Health Personnel; Healthcare; Human; Hypoglycemia; Light; Low Birth Weight Infant; Mediating; Medicaid; Mental Health; Mothers; Nature; Neonatal; Neurodevelopmental Disorder; Neurotransmitters; Obsessive-Compulsive Disorder; Outcome; Panic Disorder; Pathological anxiety; Perinatal; Pharmaceutical Preparations; Pharmacological Treatment; Phobias; Physical Function; Placenta; Post-Traumatic Stress Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnant Women; Premature Birth; Prevalence; Privatization; Psyche structure; Psychiatry; Public Health; Recommendation; Relative Risks; Reporting; Research; Risk; Role; Safety; Scanning; Sleep Disorders; Sleeplessness; Small for Gestational Age Infant; Social Anxiety Disorder; Specific qualifier value; Spontaneous abortion; Testing; Therapeutic Intervention; Time; Vulnerable Populations; Woman; adverse pregnancy outcome; clinically relevant; clinically significant; cohort; design; early pregnancy; experience; gamma-Aminobutyric Acid; hypnotic; in utero; individualized medicine; innovation; malformation; medication safety; multidisciplinary; neonatal outcome; novel; offspring; population based; postnatal development; prenatal exposure; prevent; respiratory; sedative

Anxiety disorders comprise a spectrum of conditions, including panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder, social anxiety disorder, and phobias. Their lifetime prevalence among women has been reported to be as high as 30%, so these disorders frequently complicate pregnancy. Insomnia is also very common during pregnancy, with a prevalence of nearly 40%. Pharmacological treatment with benzodiazepines or non-benzodiazepine sedative hypnotics is frequently indicated for severe anxiety and insomnia; approximately 4% of pregnant women uses one of these classes of medication during their pregnancy. Polytherapy among women using these medications is common, with 30- 40% being co-prescribed at least two additional psychotropic medications. Benzodiazepines and non- benzodiazepine sedative hypnotics cross the human placenta and may therefore have the potential to alter normal intrauterine development of fetal growth, anatomic structures, physical functioning, and postnatal development. The American College of Obstetricians and Gynecologists recommends that decisions regarding mental health treatment during pregnancy be made jointly between a woman and her mental and obstetrical health providers prior to pregnancy. Unfortunately, rigorous and comprehensive safety data to inform the risk-benefit trade-off are sparse, evidence is conflicting, and numerous safety concerns have been raised. The objective of the proposed studies is to address this critical information gap by generating high-quality evidence on the safety of benzodiazepines and non-benzodiazepine sedative hypnotics during pregnancy considering a broad range of clinically relevant adverse pregnancy outcomes, including major congenital malformations, spontaneous abortion, preterm birth, low birth weight, small for gestational age, hypoglycemia, respiratory problems, NICU admission, and neurodevelopmental disorders. The use of large, population-based cohorts of publicly and privately insured pregnant women (N ≈ 4.5 million) will enable quantification of effects with great precision, as well as exploration of the effects for specific drugs, doses, gestational timing of exposure, and polytherapy. As is the case for all studies evaluating drug safety in pregnancy given that they are observational in nature by necessity, the most important challenges relate to the potential for confounding, as well as misclassification of exposures and outcomes as documented in existing healthcare data. The project will benefit from the multidisciplinary team’s deep experience and established track record overcoming these challenges in perinatal psychiatry research using highly innovative design and advanced computational approaches. The findings will have a direct and large public health impact by enabling treatment to be tailored for the large number of women that struggle with perinatal anxiety and sleep disorders.

焦虑症包括一系列疾病，包括恐慌症、广泛性焦虑症、 强迫症、创伤后应激障碍、社交焦虑症和恐惧症。他们的 据报道，女性的终生患病率高达30%，因此这些疾病经常发生 使怀孕复杂化。失眠在怀孕期间也很常见，患病率接近40%。 经常使用苯二氮卓类或非苯二氮卓类镇静催眠药进行药物治疗 用于严重焦虑和失眠；大约4%的孕妇使用这些类别中的一种 在她们怀孕期间服用药物。在使用这些药物的女性中，综合疗法是很常见的，30- 40%的患者同时服用至少两种额外的精神药物。苯二氮卓类和非 苯二氮卓类镇静催眠药穿过人体胎盘，因此可能会改变 胎儿生长、解剖结构、身体功能和出生后的正常宫内发育 发展。 美国妇产科医师学会建议，有关心理健康的决定 怀孕期间的治疗应由妇女及其精神和产科保健提供者共同进行 在怀孕前。不幸的是，严格而全面的安全数据为风险和利益的权衡提供了信息 证据稀少，证据相互矛盾，并提出了许多安全问题。该计划的目标是 拟议的研究旨在通过生成关于安慰剂安全性的高质量证据来解决这一关键信息差距 孕期服用苯二氮卓类和非苯二氮卓类镇静催眠药 临床相关的不良妊娠结局，包括严重的先天性畸形，自发性 流产、早产、低出生体重、小于胎龄、低血糖、呼吸问题、NICU 入院和神经发育障碍。 使用大量公共和私人参保的孕妇群体(N≈450万) 将能够以极高的精度量化效果，以及探索特定药物的效果， 剂量、孕期暴露时间和综合疗法。所有评估药物安全性的研究都是如此 考虑到怀孕本质上是观察性的，最重要的挑战与 可能会混淆，以及现有文件中记录的暴露和结果的错误分类 医疗保健数据。该项目将受益于多学科团队的丰富经验和建立 在围产期精神病学研究中使用高度创新的设计和 先进的计算方法。这些发现将通过以下方式对公共卫生产生直接和巨大的影响 为大量与围产期焦虑和睡眠障碍作斗争的妇女量身定做治疗方案。