It's About Time: A Survival Approach to Gestational Weight Gain and Preterm Delivery

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.