Study designs of evaluations included in the review
Eligible studies were randomised controlled trials (RCTs). All of the included trials were multicentre studies and one was multinational.
Specific interventions included in the review
Eligible studies compared a combination of vitamins C and E with placebo. Studies in which another antioxidant was combined with vitamins C and E, or which studied only vitamin C or vitamin E compared with placebo, were excluded. In all of the included trials, the vitamin C dose was 1,000 mg and the vitamin E dose was 400 mg.
Participants included in the review
Studies of pregnant women were eligible for inclusion. The mean age of the women in the included trials, where reported, was between 26 and 31 years. Three of the 4 included trials enrolled women at high risk of pre-eclampsia, while the remaining trial enrolled patients with no or few risk factors for pre-eclampsia.
Outcomes assessed in the review
Studies where the primary outcome was pre-eclampsia or a hypertensive disorder of pregnancy were eligible. In detail, the maternal outcomes assessed included incidence of pre-eclampsia, severe pre-eclampsia, gestational hypertension and severe gestational hypertension. Infant or foetal outcomes included the incidence of foetal or neonatal loss, pre-term birth (before 37 weeks' gestation), small for gestational age (below the 10th percentile), low birth weight (under 2.5 kg) and birth weight. The secondary outcomes recorded for mothers and infants included the use of magnesium sulphate for pre-eclampsia, an Apgar score below four at 5 minutes, necrotising enterocolitis, retinopathy of prematurity and the need for mechanical ventilation.
The review only reported outcomes consistently reported across studies in the analyses. For maternal outcomes, this was only the case for pre-eclampsia; for foetuses or neonates, this was the case for foetal or neonatal loss, pre-term birth and small for gestational age.
How were decisions on the relevance of primary studies made?
Three independent investigators performed the searches and selected the studies. The results were compared and a consensus reached with the help of two further reviewers.