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

基本信息

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
项目类别：
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

项目摘要

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.

焦虑症包括一系列病症，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。据报道，女性终生患病率高达 30%，因此这些疾病经常发生妊娠期失眠也很常见，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大约 4% 的孕妇使用其中一种药物用于治疗严重焦虑和失眠；使用这些药物的妇女在怀孕期间接受多种药物治疗很常见，其中 30- 40% 的人同时服用至少两种其他精神药物和非精神药物。苯二氮卓类镇静催眠药可穿过人类胎盘，因此可能会改变胎儿生长、解剖结构、身体功能和产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由妇女及其精神和产科保健提供者共同进行不幸的是，在怀孕之前，需要严格而全面的安全数据来告知风险与收益的权衡。证据稀少，证据相互矛盾，并且提出了许多安全问题。拟议的研究旨在通过生成有关安全性的高质量证据来解决这一关键的信息差距怀孕期间使用苯二氮卓类和非苯二氮卓类镇静催眠药，考虑到多种因素临床相关的不良妊娠结局，包括重大先天畸形、自发性畸形流产、早产、低出生体重、小于胎龄、低血糖、呼吸系统问题、NICU 入院和神经发育障碍。使用大量基于人口的公共和私人保险孕妇队列（N ≈ 450 万）将能够非常精确地量化效果，并探索特定药物的效果，剂量、妊娠暴露时间和多重疗法与所有评估药物安全性的研究都是如此。鉴于妊娠本质上是观察性的，最重要的挑战与现有文件中记录的潜在的混淆以及风险暴露和结果的错误分类该项目将受益于多学科团队的丰富经验和成熟经验。使用高度创新的设计和克服围产期精神病学研究中的这些挑战的记录先进的计算方法将通过启用对公共健康产生直接和巨大的影响。为大量患有围产期焦虑和睡眠障碍的女性量身定制治疗方案。