Kinlaw Alan C, Graham Hillary L, Ananth Cande V
Division of Pharmaceutical Outcomes and Policy, University of North Carolina School of Pharmacy, Chapel Hill, North Carolina, USA.
Cecil G. Sheps Center for Health Services Research, University of North Carolina, Chapel Hill, North Carolina, USA.
Paediatr Perinat Epidemiol. 2025 Jun 5. doi: 10.1111/ppe.70010.
Generally, studies in perinatal epidemiology restrict cohort entry to 20 weeks of gestation, but exposures and outcomes may occur earlier. This restriction may introduce left truncation bias.
To examine the impact of left truncation bias when estimating the causal effect of abruption on perinatal mortality in the context of abnormal placentation, with spontaneous abortion (SAB) as a censoring event.
Through 80 Monte Carlo simulation scenarios based on realistic clinical assumptions, we estimated risk differences (RD), risk ratios (RR) and bias parameters for the abruption-perinatal mortality association.
Censoring by SAB ranged from 5.6% to 7.6% across simulation setups. The risk of mortality was underestimated in observable (left-truncated) data at ≥ 20 weeks compared to an unobservable cohort starting follow-up at placental implantation (conception cohort). Underestimation of risks was stronger among abruption pregnancies. RDs for the abruption-mortality association were biased by +1% to +3% among conceptions with normal implantation and by +5% to +43% among abnormal placentation. Due to the disproportionate underestimation of mortality among nonabruption pregnancies, RRs were overestimated by 1.1 to 1.2-fold for normal implantations and by 1.1 to 8.4-fold for abnormal implantations.
The findings of this simulation study highlight the critical importance of placentation in successful pregnancy. Abnormal placentation has profound consequences for unsuccessful pregnancies, remarkably increasing the risks of early losses, placental abruption and other obstetrical complications. This study underscores that left truncation can bias the abruption-perinatal mortality association, differentially by whether the placentation was normal or abnormal. However, defining the causal question regarding the abruption-perinatal mortality association requires consideration of the target population, which may include all conceptions. In studies of these effects, outcome follow-up capability may introduce left truncation bias. We do not prescribe one analytic approach to account for left truncation, but rather, the approach should be guided by the causal question.
一般来说,围产期流行病学研究将队列纳入限制在妊娠20周,但暴露和结局可能更早出现。这种限制可能会引入左截断偏倚。
以自然流产(SAB)作为删失事件,研究在胎盘异常情况下估计胎盘早剥对围产期死亡率的因果效应时左截断偏倚的影响。
通过基于现实临床假设的80个蒙特卡洛模拟场景,我们估计了胎盘早剥与围产期死亡率关联的风险差(RD)、风险比(RR)和偏倚参数。
在所有模拟设置中,因SAB删失的比例在5.6%至7.6%之间。与从胎盘着床开始随访的不可观察队列(受孕队列)相比≥20周时的可观察(左截断)数据中,死亡率风险被低估。在胎盘早剥妊娠中,风险低估更为明显。在着床正常的受孕中,胎盘早剥与死亡率关联的RD偏差为+1%至+3%,在胎盘异常的受孕中为+5%至+43%。由于非胎盘早剥妊娠中死亡率的低估不成比例,正常着床的RR高估了1.1至1.2倍,异常着床的RR高估了1.1至8.4倍。
本模拟研究结果突出了胎盘形成在成功妊娠中的关键重要性。胎盘异常对妊娠失败有深远影响,显著增加了早期流产、胎盘早剥和其他产科并发症的风险。本研究强调左截断会使胎盘早剥与围产期死亡率的关联产生偏倚,根据胎盘形成是否正常而有所不同。然而,定义胎盘早剥与围产期死亡率关联的因果问题需要考虑目标人群,这可能包括所有受孕情况。在这些效应的研究中,结局随访能力可能会引入左截断偏倚。我们并未规定一种分析方法来处理左截断问题,相反,该方法应由因果问题来指导。