National Institute of Environmental Health Sciences, P.O. Box 12233, Durham, NC, 27709, USA.
Department of Obstetrics and Gynecology, McGill University, Montreal, QC, Canada.
Eur J Epidemiol. 2018 Jun;33(6):523-530. doi: 10.1007/s10654-018-0373-0. Epub 2018 Mar 7.
Preterm delivery is one of the strongest predictors of neonatal mortality. A given exposure may increase neonatal mortality directly, or indirectly by increasing the risk of preterm birth. Efforts to assess these direct and indirect effects are complicated by the fact that neonatal mortality arises from two distinct denominators (i.e. two risk sets). One risk set comprises fetuses, susceptible to intrauterine pathologies (such as malformations or infection), which can result in neonatal death. The other risk set comprises live births, who (unlike fetuses) are susceptible to problems of immaturity and complications of delivery. In practice, fetal and neonatal sources of neonatal mortality cannot be separated-not only because of incomplete information, but because risks from both sources can act on the same newborn. We use simulations to assess the repercussions of this structural problem. We first construct a scenario in which fetal and neonatal factors contribute separately to neonatal mortality. We introduce an exposure that increases risk of preterm birth (and thus neonatal mortality) without affecting the two baseline sets of neonatal mortality risk. We then calculate the apparent gestational-age-specific mortality for exposed and unexposed newborns, using as the denominator either fetuses or live births at a given gestational age. If conditioning on gestational age successfully blocked the mediating effect of preterm delivery, then exposure would have no effect on gestational-age-specific risk. Instead, we find apparent exposure effects with either denominator. Except for prediction, neither denominator provides a meaningful way to define gestational-age-specific neonatal mortality.
早产是新生儿死亡的最强预测因素之一。某种暴露可能直接增加新生儿死亡的风险，也可能通过增加早产的风险间接增加新生儿死亡的风险。评估这些直接和间接影响的努力受到以下事实的影响：新生儿死亡来自两个不同的分母（即两个风险组）。一个风险组包括易受宫内病理（如畸形或感染）影响的胎儿，这可能导致新生儿死亡。另一个风险组包括活产儿，他们（与胎儿不同）易受不成熟和分娩并发症的影响。实际上，胎儿和新生儿来源的新生儿死亡无法分开——不仅因为信息不完整，而且因为来自两个来源的风险都可能对同一新生儿产生影响。我们使用模拟来评估这个结构问题的影响。我们首先构建一个情景，其中胎儿和新生儿因素分别对新生儿死亡做出贡献。我们引入一种暴露，这种暴露会增加早产（从而增加新生儿死亡）的风险，而不会影响新生儿死亡风险的两个基线组。然后，我们使用特定胎龄的胎儿或活产儿作为分母，计算暴露和未暴露的新生儿的明显胎龄特异性死亡率。如果在胎龄上进行条件化成功阻断了早产的中介作用，那么暴露对胎龄特异性风险就没有影响。相反，我们发现无论使用哪个分母，都存在明显的暴露效应。除了预测，这两个分母都没有提供一种有意义的方法来定义胎龄特异性的新生儿死亡率。
