Zika virus (ZIKV) infection during pregnancy is associated with microcephaly and other birth defects, collectively termed Congenital Zika Syndrome (CZS). During the epidemic in 2015-16, ZIKV spread through the Americas and quickly joined the list of other known teratogenic pathogens, TORCH. Multiple ZIKV vaccines have been developed for protection of pregnant women and women of childbearing age. However, ZIKV infection incidence has since waned substantially, and adverse birth outcomes are rare outcomes of infection. Studying a vaccine's protective efficacy against CZS in a large phase III clinical trial may be infeasible in such times of low incidence. Should trials be initiated, researchers may resort to alternative clinical endpoints. In this study, we simulate a variety of vaccine clinical trial scenarios to evaluate the feasibility of the CZS endpoint in vaccine studies and compare CZS to other potential outcomes: ZIKV infection detected through weekly, biweekly, or monthly testing and laboratory-confirmed, symptomatic Zika Virus Disease. We compare the sample size required for 80% statistical power to detect vaccine efficacy and trial duration for each scenario. Our results show the feasibility of CZS clinical endpoints depends on the timing of simulated clinical trials in the course of a seasonal epidemic, due to CZS risk varying with trimester of infection. This result highlights additional considerations needed when designing vaccine efficacy trials of protection against teratogenic pathogens.