Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York City, New York, USA.
Environ Health Perspect. 2021 Apr;129(4):47001. doi: 10.1289/EHP7961. Epub 2021 Apr 1.
Studies of the effects of prenatal environmental exposures on postnatal outcomes are particularly vulnerable to live birth bias; i.e., the bias that arises from the necessary restriction of the analysis to live births when that is influenced by both the exposure under study and unmeasured factors that also affect the outcome.
In the context of a recent publication of nitrogen dioxide () and autism spectrum disorder (ASD) that found an odds ratio (OR) of 0.77 per during pregnancy, we aimed to examine what parameters would be needed to account for this protective association through live birth bias.
We simulated the magnitude of bias under two selection mechanisms and when both mechanisms co-occur, assuming a true null effect. Simulation input parameters were based on characteristics of the original study and a range of plausible values for the prevalence of unmeasured factor and the ORs for the selection effects (i.e., the effects of and on loss and of on ASD). Each scenario was simulated 1,000 times.
We found that the magnitude of bias was small when and independently influenced pregnancy loss (collider-stratification without interaction), was stronger when loss preferentially occurred in (depletion of susceptibles), and was strongest when both mechanisms worked together. For example, ORs of 3.0 for , -loss, -ASD, and yielded ORs per of 0.95, 0.89, and 0.75 for the three scenarios, respectively. The bias is amplified with multiple , yielding ORs as low as 0.51.
Our simulations illustrate that live birth bias may lead to exposure-outcome associations that are biased downward, where the extent of the bias depends on the fetal selection mechanism, the strength of that selection, and the prevalence of . https://doi.org/10.1289/EHP7961.
研究产前环境暴露对产后结果的影响特别容易受到活产偏倚的影响；即，由于分析必须限于活产，而这种限制受到研究中的暴露以及也影响结果的未测量因素的影响，从而产生的偏倚。
在最近发表的一项关于二氧化氮（）和自闭症谱系障碍（ASD）的研究中，我们发现怀孕期间每增加 ，比值比（OR）为 0.77，我们旨在研究通过活产偏倚来解释这种保护关联需要哪些参数。
我们模拟了两种选择机制下的偏倚程度，以及当两种机制同时发生时，假设真实的零效应。模拟输入参数基于原始研究的特征以及未测量因素的流行率和选择效应（即 和 对妊娠丢失的影响以及 对 ASD 的影响）的合理范围的可能值。每个方案都模拟了 1000 次。
我们发现，当 和 独立影响妊娠丢失时（没有交互作用的共集分层），偏倚的程度较小，当 丢失优先发生在 时（易感者的消耗），偏倚程度更强，当两种机制同时作用时，偏倚程度最强。例如，对于 和 ，OR 分别为 3.0 的情况下，对于这三种情况， 每增加 导致的 OR 分别为 0.95、0.89 和 0.75。随着 的增加，偏倚会放大，导致的 OR 低至 0.51。
我们的模拟表明，活产偏倚可能导致暴露-结果关联向下偏倚，偏倚的程度取决于胎儿选择机制、该选择的强度以及 的流行率。https://doi.org/10.1289/EHP7961.
