当暴露影响亚组成员身份时：在围产期流行病学及其他领域构建相关因果问题
When exposure affects subgroup membership: Framing relevant causal questions in perinatal epidemiology and beyond
AI总结：
针对暴露会改变活产人群构成的问题，本文提出条件总效应与条件随机直接效应，并以 SEARCH 研究量化 HIV 检测治疗干预对婴儿无 HIV 生存的影响。
摘要：
围产期流行病学通常旨在评估暴露对婴儿结局的影响。当暴露影响分娩活产婴儿者的构成时（例如，通过影响生育力、行为或出生结局），这种“活产过程”会介导暴露对婴儿结局的影响。此前针对该情形提出的因果估计量包括：对复合出生与婴儿结局的总暴露效应、受控直接效应（例如强制出生）以及主层直接效应。以 SEARCH 研究中的围产期 HIV 传播作为启发性示例，我们提出两种替代因果估计量：1）条件总效应；以及 2）条件随机直接效应，后者是在一项假设干预下构建的，即从某个分布（可能以协变量为条件）中抽取中介变量值。所提出的条件总效应包含干预通过改变发生活产者的类型以及出生时机而产生的影响。所提出的条件随机直接效应则分离暴露对婴儿结局的效应，排除通过该活产过程产生的任何影响。在 SEARCH 中，该方法在研究基线时明确界定的 HIV 感染育龄女性目标人群内，量化了在干预对活产过程没有任何影响的情况下，一项普遍检测与治疗干预对婴儿无 HIV 生存的影响。我们的方法对广泛评估围产期流行病学中的干预效应具有意义，也适用于任何关注某一亚组内因果效应且暴露会影响该亚组成员身份的情形。
英文摘要：
Perinatal epidemiology often aims to evaluate exposures on infant outcomes. When the exposure affects the composition of people who give birth to live infants (e.g., by affecting fertility, behavior, or birth outcomes), this "live birth process" mediates the exposure effect on infant outcomes. Causal estimands previously proposed for this setting include the total exposure effect on composite birth and infant outcomes, controlled direct effects (e.g., enforcing birth), and principal stratum direct effects. Using perinatal HIV transmission in the SEARCH Study as a motivating example, we present two alternative causal estimands: 1) conditional total effects; and 2) conditional stochastic direct effects, formulated under a hypothetical intervention to draw mediator values from some distribution (possibly conditional on covariates). The proposed conditional total effect includes impacts of an intervention that operate by changing the types of people who have a live birth and the timing of births. The proposed conditional stochastic direct effects isolate the effect of an exposure on infant outcomes excluding any impacts through this live birth process. In SEARCH, this approach quantifies the impact of a universal testing and treatment intervention on infant HIV-free survival absent any effect of the intervention on the live birth process, within a clearly defined target population of women of reproductive age with HIV at study baseline. Our approach has implications for the evaluation of intervention effects in perinatal epidemiology broadly, and whenever causal effects within a subgroup are of interest and exposure affects membership in the subgroup.
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