Maternal use of prescribed opioid analgesics and risk of adverse offspring outcomes

母亲使用处方阿片类镇痛药和后代不良后果的风险

• 批准号: 10112875
• 负责人: Brian M D'Onofrio
• 金额: $ 39.74万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10112875
• 关键词: Acetaminophen; Address; Adverse effects; Age; Analgesics; Animal Model; Attention deficit hyperactivity disorder; Basic Science; Behavior; Benefits and Risks; Birth; Brain; Characteristics; Child; Clinical; Congenital Abnormality; Data; Data Set; Decision Making; Development; Evaluation; Exposure to; Female; Female of child bearing age; First Pregnancy Trimester; General Population; Gestational Age; Goals; Human; Individual; Low Birth Weight Infant; Measures; Medicaid; Medical; Methods; Morbidity - disease rate; Mothers; Neighborhoods; Neurodevelopmental Disorder; Neurodevelopmental Problem; Observational Study; Opioid Analgesics; Outcome; Pain; Pain management; Patients; Pharmaceutical Preparations; Physicians; Pregnancy; Pregnant Women; Premature Birth; Prevalence; Public Health; Recommendation; Regimen; Reporting; Research; Research Personnel; Risk; Risk Estimate; Role; Safety; Sampling; Second Pregnancy Trimester; Siblings; Socioeconomic Factors; Source; Structural Congenital Anomalies; Testing; Third Pregnancy Trimester; Time; Translating; Woman; active comparator; adverse birth outcomes; adverse outcome; autism spectrum disorder; base; child bearing; cohort; comorbidity; comparison group; design; expectation; fetal opioid exposure; illicit opioid; improved; innovation; medical specialties; mortality; offspring; opioid use; opioid use disorder; population based; pregnant; prenatal influence; prescription opioid; programs; socioeconomics

Prescribed opioid analgesic (POA) use for the treatment of pain is common among women of childbearing age and pregnant women. Despite its prevalence, however, little is known about the effects of POA use in pregnancy on offspring development. Animal models demonstrate that prenatal opioid exposure can alter brain development and behavior, but whether this translates to risks for neurodevelopmental disorders in humans is not known. Findings from the few observational studies of POA use in pregnancy and birth outcomes are mixed and limited by poor study quality, including inadequate control for confounding. The current proposal seeks to address these limitations through comprehensive analysis of a large population-based sample. In particular, the objective of the current proposal is to improve our understanding of the use and safety of POAs in pregnancy, focusing on adverse birth outcomes (structural birth defects, small size for gestational age, and preterm birth) and neurodevelopmental disorders (autism spectrum and attention-deficit/hyperactivity disorders). We propose to analyze an unparalleled, nation-wide dataset of 1.25 million Swedish children born 2006-2017, which includes detailed assessment of POA use in pregnancy, birth outcomes and neurodevelopmental disorders, and a wide range of factors that could influence the likelihood of both treatment and offspring outcomes. Furthermore we propose to use and combine multiple advanced methods of analysis. In addition to adjustment for measured factors, we will use several types of comparison groups to help evaluate the role of unmeasured confounding, including siblings, offspring of mothers using another pain medication (i.e., prescribed acetaminophen as an active comparator), and offspring of mothers using POAs before but not during pregnancy. Finally, we also will evaluate the associations with paternal POA use during pregnancy as a negative control. Preliminary analyses demonstrating that POA use during pregnancy is associated with adverse offspring outcomes, but also with many psychiatric and socioeconomic factors associated with the offspring outcomes, highlight the importance of our proposal. The proposed research is significant because it will provide a greater description of the patient characteristics that influence POA use during pregnancy, as well as a better understanding of the specific risks of the practice for offspring outcomes associated with significant morbidity and mortality. The proposal is innovative due to (a) the use of unparalleled data drawn from the linkage of numerous national registers that provide precise measures for key constructs; (b) the use of multiple advanced methods and systematic evaluation of the validity of their assumptions; and (c) a unique interdisciplinary team of researchers. The results will provide critical information for medical decision-making regarding the pain management with POAs in pregnancy and among women of childbearing age, inform ensuing research to identify offspring at greatest risk of adverse outcomes related to POA use, and guide subsequent basic research into mechanisms behind the effects of fetal opioid exposure.

使用处方阿片类镇痛药 (POA) 治疗疼痛在育龄妇女中很常见 和孕妇。然而，尽管 POA 很流行，但人们对 POA 的使用效果知之甚少。 妊娠对后代发育的影响。动物模型证明产前阿片类药物暴露会改变大脑 发育和行为，但这是否会转化为人类神经发育障碍的风险 不知道。少数关于 POA 在妊娠和分娩结果中使用的观察性研究的结果是 由于研究质量差，包括对混杂因素的控制不充分，混合和限制。目前的提案 旨在通过对大量人口样本的综合分析来解决这些局限性。在 特别是，当前提案的目标是提高我们对 POA 的使用和安全性的理解 怀孕期间，重点关注不良出生结局（结构性出生缺陷、小于胎龄儿和 早产）和神经发育障碍（自闭症谱系和注意力缺陷/多动症） 障碍）。我们建议分析一个无与伦比的全国数据集，其中包含 125 万瑞典出生儿童 2006-2017 年，其中包括对 POA 在妊娠、分娩结果和 神经发育障碍，以及可能影响两种治疗可能性的多种因素 和后代的结果。此外，我们建议使用和结合多种先进的分析方法。 除了调整测量因素外，我们还将使用几种类型的比较组来帮助 评估不可测量的混杂因素的作用，包括兄弟姐妹、使用另一种痛苦的母亲的后代 药物（即处方对乙酰氨基酚作为活性比较剂），以及使用 POAs 的母亲的后代 怀孕前但不是怀孕期间。最后，我们还将评估与父亲在生育期间使用 POA 的关联。 妊娠作为阴性对照。初步分析表明，怀孕期间使用 POA 与不良后代结局相关，但也与许多精神和社会经济因素有关 与后代的结果相关，强调我们建议的重要性。拟议的研究是 意义重大，因为它将提供对影响 POA 使用的患者特征的更多描述 怀孕期间，以及更好地了解这种做法对后代结果的具体风险 与显着的发病率和死亡率相关。该提案之所以具有创新性，是因为 (a) 使用了无与伦比的 从众多国家登记册的链接中提取的数据，为关键结构提供精确的衡量标准； (b) 使用多种先进方法并系统评估其假设的有效性；和 (c) 独特的跨学科研究团队。结果将为医疗提供重要信息 关于妊娠期和育龄期妇女使用 POAs 进行疼痛管理的决策 年龄，为随后的研究提供信息，以确定与 POA 使用相关的不良后果风险最大的后代，以及 指导后续对胎儿阿片类药物暴露影响背后机制的基础研究。