Suarez Elizabeth A, Landi Suzanne N, Conover Mitchell M, Jonsson Funk Michele
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
Pharmacoepidemiol Drug Saf. 2018 Mar;27(3):307-314. doi: 10.1002/pds.4387. Epub 2018 Jan 17.
Administrative claim databases are increasingly being used to study the safety of medication exposures during pregnancy. These studies are restricted to live births due to a reliance on algorithms for estimating gestational age that are based on codes associated with live delivery. Conditioning on live birth may induce selection bias when studying the effect of a drug on a pregnancy complication if fetal death is a competing risk for the complication or is caused by the complication.
We simulated a population of 100,000 pregnancies and estimated the impact of selection bias on relative estimates for the effect of antidepressant exposure on the outcome of preeclampsia. We assumed that the exposure, outcome, and covariates increased the risk of fetal loss.
A downward bias in the risk ratio was consistently observed when conditioning on live births. When an unmeasured covariate was assumed to be a common cause of fetal death, antidepressant use, and preeclampsia, the direction of bias varied depending on the strength of the confounding relationship coupled with the selection bias. Despite the very low prevalence of stillbirth, the strength of the relationship between antidepressant use and stillbirth had a substantial impact on bias.
Conditioning on live birth can be problematic when studying pregnancy complications. Simple quantitative selection bias analysis in populations restricted to live births may not fully account for selection bias.
行政索赔数据库越来越多地用于研究孕期药物暴露的安全性。由于依赖基于与活产相关代码的算法来估计孕周，这些研究仅限于活产。如果胎儿死亡是并发症的竞争风险或由并发症引起，那么在研究药物对妊娠并发症的影响时，以活产为条件可能会导致选择偏倚。
我们模拟了10万名孕妇的群体，并估计了选择偏倚对抑郁症药物暴露对子痫前期结局的相对估计值的影响。我们假设暴露、结局和协变量会增加胎儿丢失的风险。
以活产为条件时，始终观察到风险比存在向下偏倚。当假定一个未测量的协变量是胎儿死亡、抗抑郁药使用和子痫前期的共同原因时，偏倚的方向会因混杂关系的强度以及选择偏倚而有所不同。尽管死产的发生率非常低，但抗抑郁药使用与死产之间关系的强度对偏倚有很大影响。
在研究妊娠并发症时，以活产为条件可能会出现问题。在仅限于活产的人群中进行简单的定量选择偏倚分析可能无法完全解释选择偏倚。
