wo-sided test is assumed in the sample size calculation. Based on the literature [39], the best estimation of incidence of PE in the high risk population is 12%. With an alpha error of 5% and a power of >90%, 3,064 women (1,532 in each group) are required to demonstrate a decrease of 30% in the incidence of PE (from 12% to 8.4%) in the trial group (4.0 mg of folic acid) as compared with the placebo group [40]. We will recruit 3,656 high risk women within the study period. This will allow for noncompliance, withdrawn, loss to follow up, and other unanticipated events. The power in our study to detect 30% reduction of PE is 90%. Based on findings from observational studies, all showed unanimously a 30% or more reduction in PE in the supplementation group, suggesting that a 30% reduction in the trial arm as compared with placebo arm is achievable. Moreover, a 30% reduction would be considered clinically important.
We anticipate a rate of loss to follow up of