here 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 (HR 0.89, 95%
CI: 0.84 to 0.93). Properly accounting for the confounding effect of time using a
survival model, however, mitigates this bias (HR 0.98, 95% CI: 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