The distribution of baseline and pregnancy characteristics was similar between the two groups.

Pre-eclampsia is a serious medical condition, affecting about 3-5% of pregnancies,1 2 accounting for more than 35 000 maternal deaths annually worldwide and an important factor in maternal morbidity.1 3 4

Future directions for this research include exploration of the increased risk of pre-eclampsia in mothers carrying twins and using high dose folic acid, and the potential protective effect of folic acid on perinatal death warrants ongoing study

The data coordinating centre managed treatment allocation, and all participants, site investigators, coordinators and other research staff, and members of the trial coordinating centre were blinded to treatment allocation after randomisation. No unmasking occurred during the trial.

FACT has several notable strengths. Firstly, it was designed to be as conclusive as possible in a rigorous,large, randomised, double blinded, placebo controlled, phase III, international and multicentre trial.

Among participants with primary outcome data available (n=2301), 169 (14.8%) in the folic acid group had a diagnosis of pre-eclampsia compared with 156 (13.5%) in the placebo group (relative risk 1.10, 95%confidence interval 0.90 to 1.34, P=0.37).

The current study, the Folic Acid Clinical Trial (FACT), was designed and conducted to evaluate the effect of daily supplementation with 4.0 mg folic acid beyond the first trimester on the risk of developing pre-eclampsia among pregnant women at high risk for this condition

We excluded women if they had a known fetal anomaly or fetal death, a history of maternal medical complications (including renal disease with altered renal function) or epilepsy, cancer, or current use of folic acid antagonists.

Baseline data was collected

Between-group comparison of data was carried out.

Data was collected 1 year after treatment was started

The number of withdrawals was calculated

Within-patient data were analyzed in terms of changes in outcome measures