Mitchell Emily M, Hinkle Stefanie N, Schisterman Enrique F
From the Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD.
Epidemiology. 2016 Mar;27(2):182-7. doi: 10.1097/EDE.0000000000000413.
There is substantial interest in understanding the impact of gestational weight gain on preterm delivery (delivery <37 weeks). The major difficulty in analyzing the association between gestational weight gain and preterm delivery lies in their mutual dependence on gestational age, as weight naturally increases with increasing pregnancy duration. In this study, we untangle this inherent association by reframing preterm delivery as time to delivery and assessing the relationship through a survival framework, which is particularly amenable to dealing with time-dependent covariates, such as gestational weight gain. We derive the appropriate analytical model for assessing the relationship between weight gain and time to delivery when weight measurements at multiple time points are available. Since epidemiologic data may be limited to weight gain measurements taken at only a few time points or at delivery only, we conduct simulation studies to illustrate how several strategically timed measurements can yield unbiased risk estimates. Analysis of the study of successive small-for-gestational-age births demonstrates that a naive analysis that does not account for the confounding effect of time on gestational weight gain suggests a strong association between higher weight gain and later delivery (hazard ratio: 0.89, 95% confidence interval = 0.84, 0.93). Properly accounting for the confounding effect of time using a survival model, however, mitigates this bias (hazard ratio: 0.98, 95% confidence interval = 0.97, 1.00). These results emphasize the importance of considering the effect of gestational age on time-varying covariates during pregnancy, and the proposed methods offer a convenient mechanism to appropriately analyze such data.See Video Abstract at http://links.lww.com/EDE/B13.
了解孕期体重增加对早产（孕周<37周分娩）的影响受到广泛关注。分析孕期体重增加与早产之间关联的主要困难在于它们对孕周存在相互依赖性，因为体重会随着孕期延长而自然增加。在本研究中，我们通过将早产重新定义为分娩时间，并通过生存框架评估二者关系来理清这种内在关联，该框架特别适合处理诸如孕期体重增加这类随时间变化的协变量。当有多个时间点的体重测量数据时，我们推导了评估体重增加与分娩时间关系的合适分析模型。由于流行病学数据可能仅限于在少数几个时间点或仅在分娩时进行的体重增加测量，我们进行了模拟研究，以说明几次策略性定时测量如何能得出无偏风险估计。对连续小于胎龄儿出生的研究分析表明，未考虑时间对孕期体重增加的混杂效应的简单分析显示，体重增加较高与分娩较晚之间存在强关联（风险比：0.89，95%置信区间=0.84，0.93）。然而，使用生存模型恰当地考虑时间的混杂效应可减轻这种偏差（风险比：0.98，95%置信区间=0.97，1.00）。这些结果强调了在孕期考虑孕周对随时间变化的协变量影响的重要性，并且所提出的方法提供了一种方便的机制来恰当地分析此类数据。见视频摘要：http://links.lww.com/EDE/B13 。
