Bayesian Mediation Analysis for Neonatal Neurodevelopmental Outcomes in Pregnancy with Opioid Exposure

阿片类药物暴露妊娠期新生儿神经发育结果的贝叶斯中介分析

• 批准号: 10176650
• 负责人: Xuerong Wen
• 金额: $ 25.67万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10176650
• 关键词: 6 year old; Alcohols; Animals; Anxiety; Attention deficit hyperactivity disorder; Award; Bayesian Method; Bayesian Modeling; Behavioral; Birth Certificates; Child; Child Development; Childhood; Classification; Clinical; Cognitive; Congenital Abnormality; Data; Data Analyses; Data Set; Data Sources; Detection; Development; Developmental Delay Disorders; Educational Assessment; Educational Status; Ensure; Exposure to; Fetal safety; Funding; Goals; Health; Incidence; Infant Health; Knowledge; Link; Logistic Regressions; Low Birth Weight Infant; Markov chain Monte Carlo methodology; Maternal Exposure; Mediating; Mediation; Mediator of activation protein; Medical; Mental Depression; Methods; Minor; Modeling; Mothers; Neonatal; Neonatal Abstinence Syndrome; Neurologist; Newborn Infant; Opioid; Outcome; Outcome Study; Pain management; Parents; Pathway interactions; Performance; Perinatal; Perinatal Care; Perinatal Exposure; Pharmaceutical Preparations; Pregnancy; Pregnant Women; Public Health; Records; Research; Research Design; Research Personnel; Resources; Risk; Role; Safety; Sample Size; Sampling; Signal Transduction; Social Sciences; Statistical Data Interpretation; Statistical Models; Structural Models; Testing; Time; United States; Work; adverse outcome; adverse pregnancy outcome; autism spectrum disorder; base; clinically relevant; epidemiology study; experience; fetal; fetal opioid exposure; flexibility; follow-up; improved; in utero; interest; kindergarten; malformation; maternal opioid use; medication safety; multilevel analysis; neonatal outcome; neurobehavioral; neurodevelopment; neuron apoptosis; obstetric outcomes; offspring; opioid exposure; opioid overdose; opioid use; opioid use in pregnancy; overdose death; prenatal exposure; prescription opioid; response; safety study; screening; skills; statistics; third grade; tool

Contact PD/PI: Wen, Xuerong ABSTRACT Mediation analysis is useful to quantify the direct and indirect relationship among maternal opioid exposure during pregnancy, short-term adverse neonatal outcomes, and long-term neurodevelopmental outcomes in children. There are different approaches to estimate mediation models, and Bayesian methods offer some advantages compared to their frequentist counterparts: possibility of including prior information, computational feasibility when a multilevel model structure is needed, and more flexibility in analyzing data with smaller sample sizes. In conducting the originally funded project (1R15HD097588), we have observed significant effects for pregnancy opioid exposure on multiple short-term congenital malformations and long-term neurodevelopmental outcomes in children. However, it is unclear whether the observed effects are direct or indirect, and whether the effect of maternal opioid usage on neonatal development remains significant after adjusting for mediation factors. The limited data sources restrain our knowledge and creates a formidable research opportunity. In this project, we will investigate mediation effects of maternal opioid use on multiple short- and long-term adverse pregnancy outcomes for children. Two linked datasets will be used to examine different outcomes, provide a long follow-up time, and validate the estimation of pregnancy window. Our findings from the originally awarded project have shown that prescription opioid use in pregnant women is associated with increased risk of congenital malformations and neonatal neurodevelopmental outcomes. It is necessary to further adjust for the mediation factors and determine the direct effects of opioid exposure during pregnancy. The focus of this project is to study the relationship between perinatal opioid exposure and adverse health outcomes in children. We hypothesize that prescription opioid use during pregnancy directly poses risks on long-term development of children, and that optimized pain management in pregnant women improves long-term health outcomes for children. Specific Aim 1: To identify the mediation factors that are on the causal pathway of maternal exposure to prescription opioids and neonatal neurodevelopmental outcomes. The goal of this aim is to identify the mediators that are significantly associated with maternal opioid exposure and also strongly correlated with child long-term neurodevelopmental outcomes. First, we will fit a multivariable logistic regression model to assess the association between short-term adverse neonatal outcomes and in-utero opioid exposure after adjusting for baseline potential confounding factors. Second, parametric and non-parametric correlations will be assessed for long-term neurodevelopmental outcomes and short-term adverse neonatal outcomes that are significantly related to in-utero opioid exposure. Third, a mediating risk scores will be calculated based on all selected mediators. Specific Aim 2: To formulate and estimate a Bayesian mediation model for the long-term neonatal neurodevelopmental outcome First, we will formulate a Bayesian mediation analysis model. The specification of a Bayesian mediation model requires the prior distribution elicitation for the unknown parameters, using information from previous studies when available, and a sampling distribution for the response or mediation variable. The choice of default priors allows for comparison with frequentist methods. Second, Markov Chain Monte Carlo methods (MCMC) will be applied to estimate Bayesian models. Posterior distributions will be obtained for all the parameters of interest, in particular for the effect of maternal opioid exposure during pregnancy. Posterior distribution analysis allows for the extraction of summary statistics of interest, posterior means, medians, and credible intervals. Robustness of results will be assessed for different prior distribution choices. Outcome: This work will significantly impact the field of opioid safety in pregnancy by accurately quantifying the association between perinatal exposure to prescription opioids with long term neurodevelopment and educational status in children. Project Summary/Abstract

联系人 PD/PI：文雪蓉 抽象的 中介分析有助于量化母亲阿片类药物暴露期间的直接和间接关系 妊娠、短期不良新生儿结局以及儿童长期神经发育结局。有 估计中介模型的不同方法，贝叶斯方法与其相比具有一些优势 频率论对应物：包括先验信息的可能性，多级模型时的计算可行性 需要结构，并且需要更灵活地分析较小样本量的数据。在进行最初资助的 项目（1R15HD097588），我们观察到妊娠期阿片类药物暴露对多种短期的显着影响 儿童先天畸形和长期神经发育结果。然而，尚不清楚是否 观察到的影响是直接的还是间接的，以及母亲使用阿片类药物对新生儿发育的影响是否仍然存在 调整中介因素后显着。有限的数据源限制了我们的知识并创造了强大的 研究机会。在这个项目中，我们将研究母亲使用阿片类药物对多种短期和 对儿童的长期不良妊娠结局。两个链接的数据集将用于检查不同的结果， 提供较长的随访时间，并验证妊娠窗口的估计。我们最初的发现 获奖项目表明，孕妇使用处方阿片类药物与妊娠风险增加有关 先天性畸形和新生儿神经发育结果。调解还需进一步调整 因素并确定怀孕期间阿片类药物暴露的直接影响。该项目的重点是研究 围产期阿片类药物暴露与儿童不良健康结果之间的关系。我们假设处方 怀孕期间使用阿片类药物直接对儿童的长期发育构成风险，并且优化疼痛 对孕妇的管理可改善儿童的长期健康结果。具体目标 1：确定 孕产妇接触处方阿片类药物和新生儿的因果途径的中介因素 神经发育结果。该目标的目的是确定与以下因素显着相关的中介者： 母亲阿片类药物暴露也与儿童长期神经发育结果密切相关。首先，我们将 拟合多变量逻辑回归模型来评估短期不良新生儿结局与 调整基线潜在混杂因素后的宫内阿片类药物暴露。二、参数化与非参数化 将评估长期神经发育结局和短期不良新生儿结局的相关性 与宫内阿片类药物暴露显着相关。第三，将根据所有选定的内容计算中介风险评分 调解员。具体目标 2：制定并估计长期新生儿的贝叶斯中介模型 神经发育结果 首先，我们将制定贝叶斯中介分析模型。规格 贝叶斯中介模型需要使用以下信息对未知参数进行先验分布推导： 先前的研究（如果有），以及响应或中介变量的抽样分布。默认的选择 先验允许与频率论方法进行比较。其次，马尔可夫链蒙特卡罗方法（MCMC）将 应用于估计贝叶斯模型。将为所有感兴趣的参数获得后验分布，特别是 妊娠期间母亲接触阿片类药物的影响。后验分布分析允许提取 感兴趣的汇总统计数据、后验均值、中位数和可信区间。将评估结果的稳健性 不同的先验分布选择。 结果：这项工作将通过准确量化阿片类药物在妊娠期的安全性领域产生重大影响 围产期处方阿片类药物暴露与长期神经发育和教育状况之间的关系 孩子们。 项目概要/摘要

项目成果

A Bayesian latent class model for predicting gestational age in health administrative data.

用于预测健康管理数据中胎龄的贝叶斯潜在类别模型。

• 发表时间: 2022-11
• 影响因子: 1.5
• 作者: Wang, Shuang;Puggioni, Gavino;Wen, Xuerong
• 通讯作者: Wen, Xuerong

Maternal Complications and Prescription Opioid Exposure During Pregnancy: Using Marginal Structural Models.

怀孕期间孕产妇并发症和处方阿片类药物暴露：使用边缘结构模型。

• 发表时间: 2021
• 影响因子: 4.2
• 作者: Wen, Xuerong;Wang, Shuang;Lewkowitz, Adam K;Ward, Kristina E;Brousseau, Erin Christine;Meador, Kimford J
• 通讯作者: Meador, Kimford J

Utilization of Antiseizure Medications in Women of Childbearing Age With Epilepsy and Nonepilepsy Indications: A Retrospective Cohort Study.

有癫痫和非癫痫症状的育龄妇女抗癫痫药物的使用：一项回顾性队列研究。

• 发表时间: 2023-09-05
• 影响因子: 9.9
• 作者: Lawal, Oluwadolapo D;Meador, Kimford J;Hume, Anne L;Wen, Xuerong
• 通讯作者: Wen, Xuerong

Association Between Prenatal Opioid Exposure and Neurodevelopmental Outcomes in Early Childhood: A Retrospective Cohort Study.

产前阿片类药物暴露与幼儿期神经发育结果之间的关联：一项回顾性队列研究。

• 发表时间: 2021-08
• 影响因子: 4.2
• 作者: Wen, Xuerong;Lawal, Oluwadolapo D;Belviso, Nicholas;Matson, Kelly L;Wang, Shuang;Quilliam, Brian J;Meador, Kimford J
• 通讯作者: Meador, Kimford J

Association of Gestational Opioid Exposure and Risk of Major and Minor Congenital Malformations.

妊娠期阿片类药物暴露与主要和轻微先天畸形风险的关联。

• 发表时间: 2021
• 影响因子: 13.8
• 作者: Wen, Xuerong;Belviso, Nicholas;Murray, Emily;Lewkowitz, Adam K;Ward, Kristina E;Meador, Kimford J
• 通讯作者: Meador, Kimford J