Gestational Age at Arrest of Development: An Alternative Approach for Assigning Time at Risk in Studies of Time-Varying Exposures and Miscarriage

The time between arrest of pregnancy development and miscarriage represents a window in which the pregnancy is nonviable and not developing. In effect, the pregnancy loss has already occurred, and additional exposure cannot influence its outcome. However, epidemiologic studies of miscarriage traditionally use gestational age at miscarriage (GAM) to assign time in survival analyses, which overestimates duration of exposure and time at risk. In Right From the Start, a pregnancy cohort study (2000-2012), we characterized the gap between estimated gestational age at arrest of development (GAAD) and miscarriage using transvaginal ultrasound in 500 women recruited from 3 states (North Carolina, Tennessee, and Texas). We compared effect estimates from models using GAAD with GAM to assign time at risk through a simulation study of several exposure patterns with varying effect sizes. The median gap between GAAD and miscarriage was 23 days (interquartile range, 15-32). Use of GAAD decreased the bias and variance of the estimated association for time-varying exposures, whereas half the time using GAM led to estimates that differed from the true effect by more than 20%. Using GAAD to assign time at risk should result in more accurate and consistent characterization of miscarriage risk associated with time-varying exposures.