A Population-Based Study to Quantify the Risks of Opioid Analgesics in Pregnancy

一项基于人群的研究，旨在量化妊娠期阿片类镇痛药的风险

• 批准号: 9807271
• 负责人: Susan B Brogly
• 金额: $ 6.2万
• 依托单位: QUEEN'S UNIVERSITY AT KINGSTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-12 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9807271
• 关键词: Acetaminophen; Address; Affect; Analgesics; Birth; Canada; Caring; Case-Control Studies; Cessation of life; Characteristics; Clinical; Code; Codeine; Cohort Studies; Congenital Abnormality; Congenital Heart Defects; Data; Databases; Defect; Discipline of obstetrics; Dose; Enrollment; Etiology; Exposure to; First Pregnancy Trimester; Goals; Health Personnel; Health Services; Healthcare; Healthcare Systems; Heart Abnormalities; Hospitalization; Hydrocodone; Ice; Infant; Institutes; Insurance; Knowledge; Link; Marketing; Medicaid; Methods; Modernization; Monitor; Mothers; Narcotics; Neonatal Abstinence Syndrome; Observational Study; Ontario; Opiate Addiction; Opioid; Opioid Analgesics; Outcome; Pain; Pain management; Pharmaceutical Preparations; Population Study; Pregnancy; Pregnant Women; Premature Birth; Prenatal care; Privatization; Provider; Province; Records; Research; Risk; Safety; Sample Size; Science; Selection Bias; Small for Gestational Age Infant; Spinal Dysraphism; Sum; System; Teratogens; Tramadol; Uncertainty; Universal Coverage; Woman; adverse outcome; adverse pregnancy outcome; beneficiary; clinical care; cohort; follow-up; foot; high dimensionality; high risk; improved; infant outcome; opioid exposure; opioid mortality; opioid overdose; opioid use; opioid use in pregnancy; oral cleft; population based; postnatal; prenatal; prenatal exposure; prescription opioid; programs; safety study; stillbirth; systematic review; treatment choice

PROJECT SUMMARY Prescription opioid use in pregnancy has increased dramatically over the past two decades. Yet, few studies have examined the impact of opioids used for pain on adverse pregnancy outcomes. Some data suggest that prenatal opioid analgesics may be associated with a higher risk of certain birth defects. However, evidence is limited by discrepant study results, poor maternal recall of medication use, and small sample sizes. In addition to these concerns, there are little data on the risk of preterm and small for gestational age birth following opioid analgesic exposure, and stillbirth has not been studied. Evidence of the safe use of prenatal opioid analgesics is thus inconclusive. The primary goal of this study is to determine the risks associated with exposure to opioids for pain in pregnancy independent of biases that have affected prior studies. We will examine several important adverse pregnancy outcomes possibly associated with such exposure including specific birth defects, preterm birth, small for gestational age birth, and stillbirth. The outcomes of maternal and infant opioid dependence following prenatal opioid analgesic exposure also will be evaluated. To achieve this goal we have assembled a population-based cohort of all pregnancies in Ontario, Canada (N≈790,000) from 2012-2017, 30,262 of which were exposed to opioid analgesics during pregnancy. Using modern methods such as high-dimensional propensity score adjustment and sensitivity analyses of alternative referents (including infants unexposed to opioid analgesics and infants unexposed to opioid analgesics but prenatally exposed to other analgesics), we will determine the associations between particular opioid analgesic exposures during the etiologically relevant windows of gestation and these maternal and infant outcomes. This will be the first study to examine the duration and dose of prenatal analgesic opioids on the risk of these adverse outcomes. Our population-based cohort study will provide estimates of the absolute risk of these outcomes, which cannot be estimated from existing US case-control studies, and which are needed to inform maternal treatment choices. Studies of the safety of prenatal medications in extant US data such as Medicaid exclude 80% of pregnancies (i.e., women with restricted benefits, capitated care, private insurance, or incomplete enrollment during pregnancy) to have complete pregnancy data, which may result in selection bias or results that cannot be generalized. Concerns of generalizability also apply to US private insurance beneficiaries. To overcome these limitations we propose a population-based cohort study using an extant database of universal healthcare coverage and complete prescription data for Ontario, Canada’s most populous province of 13 million. Clinical care and characteristics of pregnant women in the US and Canada are similar, thus the results of this study will have direct relevance for US providers and pregnant women. Better understanding of the risks of prenatal opioid analgesics will direct treatment of pain in pregnancy and management of exposed infants.

项目摘要 在过去的二十年中，妊娠处方阿片类药物的使用急剧增加。但是，很少有研究 已经检查了用于疼痛的阿片类药物对不良妊娠结局的影响。一些数据表明 产前阿片类镇痛药可能与某些先天缺陷的风险更高有关。但是，证据是 受差异研究结果的限制，对药物使用的不良召回和少量样本量。此外 就这些担忧而言，几乎没有关于早产风险的数据 镇痛暴露和死产尚未研究。安全使用产前阿片类镇痛药的证据 因此尚无定论。 这项研究的主要目标是确定与阿片类药物接触疼痛有关的风险 怀孕独立于影响先前研究的偏见。我们将研究一些重要的广告 怀孕结果可能与这种暴露有关，包括特定的先天缺陷，早产， 小针对胎龄和死产。母体和婴儿阿片类药物依赖性的结果 还将评估产前阿片类镇痛药。为了实现这一目标，我们组装了 从2012 - 2017年开始，加拿大安大略省的所有怀孕（N≈790,000），其中30,262 在怀孕期间暴露于Ooid镇痛药。使用现代方法，例如高维 倾向评分的调整和替代指南的灵敏度分析（包括婴儿意外的婴儿 绿核酸镇痛药和婴儿意外的卵巢镇痛药，但在产前暴露于其他镇痛药）， 将确定在病因相关期间特定的阿片类镇痛暴露之间的关联 妊娠窗户以及这些母亲和婴儿的结果。这将是第一个研究 产前镇痛药的持续时间和剂量对这些不良结果的风险。我们的基于人群的 队列研究将提供这些结果的绝对风险的估计，这是无法从中估算的 现有的美国病例对照研究，需要为矩阵治疗选择提供信息。 在美国额外数据中的产前药物的安全性研究，例如医疗补助不包括80％的怀孕 （即有受限制福利，大写护理，私人保险或不完整入学率的妇女 怀孕）具有完整的怀孕数据，这可能导致选择偏见或结果不能是 广义。对普遍性的担忧也适用于美国私人保险受益人。克服这些 我们提出了一项基于人群的队列研究的限制 加拿大人口最多的1300万省安大略省的覆盖范围和完整的处方数据。临床 美国和加拿大孕妇的护理和特征是相似的，因此这项研究的结果将 与美国提供者和孕妇有直接的相关性。更好地理解产前的风险 阿片类镇痛药将指导妊娠疼痛和暴露婴儿的治疗。