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

处方阿片类止痛剂(POA)用于治疗疼痛在育龄妇女中很常见 还有怀孕的女人。然而，尽管POA普遍存在，但人们对POA在 怀孕对后代发育的影响。孕期使用POA的少数观察性研究的结果 出生结果好坏参半，并受到研究质量差的限制，包括对混淆的控制不足。 目前的建议旨在通过对大量人口的全面分析来解决这些限制- 基于样本。特别是，目前提案的目的是提高我们对使用的理解 孕期POA的安全性和安全性，重点关注不利的出生结局(结构性出生缺陷，体型较小 胎龄和早产)和神经发育障碍(自闭症和注意力- 缺陷/多动障碍)。我们建议分析一个无与伦比的、全国范围内125万人的数据集 2006-2017年出生的瑞典儿童，其中包括对怀孕、分娩期间使用POA的详细评估 结果和神经发育障碍，以及可能影响 治疗和后代结果都是如此。此外，我们建议使用和结合多个先进的 分析方法。除了对测量的因素进行调整外，我们还将使用几种类型的比较 帮助评估未测量混杂的作用的团体，包括兄弟姐妹、使用 另一种止痛药，以及母亲在怀孕前但不是在怀孕期间使用POA的子女。最后，我们 还将评估怀孕期间父亲使用POA作为阴性对照的相关性。初步 分析表明，怀孕期间使用POA与不良后代结局有关，但 此外，还有许多精神和社会经济因素与后代的结果有关，强调 我们建议的重要性。拟议的研究具有重要意义，因为它将提供对 怀孕期间影响POA使用的患者特征，以及对POA的更好理解 这种做法对后代结局的具体风险与显著的发病率和死亡率有关。这个 提案具有创新性，因为(A)使用了无与伦比的数据，这些数据来自许多国家的联系 为关键构造提供精确测量的寄存器；(B)使用多种先进方法和 对其假设的正确性进行系统评估；以及(C)一个独特的跨学科团队 研究人员。研究结果将为有关疼痛的医疗决策提供关键信息。 在妊娠期和育龄妇女中对POA进行管理，通知后续研究 确定与使用POA相关的不良后果风险最大的子女，并指导后续的基本 研究胎儿阿片类药物暴露影响背后的机制。这份补充材料将支持一名学生 作为NIDA暑期研究实习计划的一部分，她在这个项目上帮助我们。

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. 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, 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. This supplement will support a student as she assists us on this project as part of NIDA’s Summer Research Internship Program.