Latour Chase D, Klose Mark, Edwards Jessie K, Song Zoey, Jonsson Funk Michele, Wood Mollie E
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Paediatr Perinat Epidemiol. 2025 Jul 7. doi: 10.1111/ppe.70043.
Pregnancy loss is recognised as a competing event in studies of prenatal medication use. A healthy live birth also precludes subsequent pregnancy outcomes, yet is often censored in time-to-event analyses.
Using a Monte Carlo simulation, we examined bias resulting from censoring versus accounting for healthy live birth as a competing event in estimates of the total effect of prenatal medication use on pregnancy outcomes.
We simulated 2000 cohorts of 7500 conceptions with chronic hypertension under 12 treatment profiles. Ongoing pregnancies were indexed into the trial and randomly assigned to initiate or not initiate antihypertensives. Using time-to-event methods, we estimated absolute risks, risk differences (RD) per 100 pregnancies, and risk ratios (RR) for two outcomes, mirroring a prior trial: (i) composite fetal death or severe prenatal preeclampsia and (ii) small for gestational age (SGA) live birth. For the composite outcome, we conducted analyses where non-preeclamptic live birth was: (1) a censoring event and (2) a competing event. For SGA live birth, we conducted analyses where fetal death and non-SGA live birth were: (1) censoring events; (2) a competing event and censoring event, respectively; and (3) competing events.
For the composite outcome, censoring non-preeclamptic live births overestimated the absolute risk by 42.3 to 49.1 percentage points; RD and RR estimates were biased (e.g., RD bias range -6.18 to 0.46). For SGA live birth, analyses censoring non-SGA live births (with or without fetal death as a competing event) overestimated absolute risk by 30.0 to 37.7 and 40.9 to 52.4 percentage points on average; RD and RR estimates were biased (e.g., RD bias range -7.45 to 0.79 and -9.62 to 1.81, respectively). Analyses in which healthy live births were modelled as competing events produced unbiased risks, RDs and RRs.
Censoring healthy live births resulted in overestimated risks as well as biased and imprecise total treatment effect estimates. Such inaccuracies about risks undermine informed patient-provider decision-making.
在产前药物使用研究中，妊娠丢失被视为一个竞争事件。健康活产同样会排除后续的妊娠结局，但在事件发生时间分析中常被截尾。
通过蒙特卡洛模拟，我们研究了在估计产前药物使用对妊娠结局的总体影响时，将健康活产作为竞争事件进行截尾与考虑该事件所导致的偏差。
我们模拟了2000个队列，每个队列有7500例患有慢性高血压的妊娠情况，设置了12种治疗方案。将正在进行的妊娠纳入试验，并随机分配以启动或不启动抗高血压药物治疗。使用事件发生时间方法，我们估计了两种结局的绝对风险、每100次妊娠的风险差异（RD）和风险比（RR），这与之前的一项试验类似：（i）复合胎儿死亡或重度产前子痫前期，以及（ii）小于胎龄（SGA）活产。对于复合结局，我们进行了分析，其中非子痫前期活产被视为：（1）一个截尾事件，以及（2）一个竞争事件。对于SGA活产，我们进行了分析，其中胎儿死亡和非SGA活产被视为：（1）截尾事件；（2）分别为竞争事件和截尾事件；以及（3）竞争事件。
对于复合结局，将非子痫前期活产截尾会使绝对风险高估42.3至49.1个百分点；RD和RR估计值存在偏差（例如，RD偏差范围为-6.18至0.46）。对于SGA活产，将非SGA活产截尾的分析（无论是否将胎儿死亡作为竞争事件）平均使绝对风险高估30.0至37.7个百分点以及高估40.9至52.4个百分点；RD和RR估计值存在偏差（例如，RD偏差范围分别为-7.45至0.79和-9.62至1.81）。将健康活产模拟为竞争事件的分析得出了无偏的风险、RD和RR。
将健康活产截尾导致风险高估以及总体治疗效果估计存在偏差且不准确。这些关于风险的不准确信息会损害医患共同的明智决策。
