Evidence from animal models and epidemiological studies has linked prenatal alcohol exposure (PAE) to a broad range of long-term cognitive and behavioural deficits. However, there is a paucity of evidence regarding the nature and levels of PAE associated with increased risk of clinically significant cognitive deficits. To derive robust and efficient estimates of the effects of PAE on cognitive function, we have developed a hierarchical meta-analysis approach to synthesize information regarding the effects of PAE on cognition, integrating data on multiple outcomes from six U.S. longitudinal cohort studies. A key assumption of standard methods of meta-analysis, effect sizes are independent, is violated when multiple intercorrelated outcomes are synthesized across studies. Our approach involves estimating the dose–response coefficients for each outcome and then pooling these correlated dose–response coefficients to obtain an estimated “global” effect of exposure on cognition. In the first stage, we use individual participant data to derive estimates of the effects of PAE by fitting regression models that adjust for potential confounding variables using propensity scores. The correlation matrix characterizing the dependence between the outcome-specific dose–response coefficients estimated within each cohort is then run, while accommodating incomplete information on some outcome. We also compare inferences based on the proposed approach to inferences based on a full multivariate analysis.

中文翻译：

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针对涉及多个队列的多种结果的设置进行分层荟萃分析


来自动物模型和流行病学研究的证据表明，产前酒精暴露 (PAE) 与一系列长期认知和行为缺陷有关。然而，关于 PAE 的性质和水平与临床显着认知缺陷风险增加相关的证据很少。为了对 PAE 对认知功能的影响进行稳健和有效的估计，我们开发了一种分层荟萃分析方法来综合有关 PAE 对认知功能的影响的信息，整合来自六项美国纵向队列研究的多种结果的数据。荟萃分析标准方法的一个关键假设是效应大小是独立的，当跨研究综合多个相互关联的结果时，就会违反这一假设。我们的方法包括估计每个结果的剂量反应系数，然后汇总这些相关的剂量反应系数，以获得暴露对认知的估计“全局”影响。在第一阶段，我们使用个体参与者数据通过拟合回归模型来得出 PAE 影响的估计，该回归模型使用倾向得分调整潜在的混杂变量。然后运行相关矩阵，表征每个队列中估计的特定结果剂量反应系数之间的依赖性，同时适应某些结果的不完整信息。我们还比较了基于所提出的基于完整多变量分析的推论方法的推论。