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This systematic review suggests that use of antioxidants during pregnancy may help reduce the risk of pre-eclampsia, but may increase the risk of preterm birth. These findings, however, come from low-quality trials and therefore this intervention cannot be recommended for implementation at the present time. Several trials evaluating vitamin C and E supplementation during either low- or high-risk pregnancy are currently ongoing, and may provide more reliable evidence to guide clinical practice.

This review analysed data form seven trials involving 6082 pregnant women taking, or not taking, different antioxidant regimens to prevent pre-eclampsia. The review examined randomized controlled and controlled clinical trials that had compared antioxidants (vitamin C, or E alone, both in combination, or selenium or lycopene) with nothing or placebo and reported on clinical outcomes, namely pre-eclampsia, preterm delivery, small-for-gestational age, perinatal mortality, birth weight and gestational age at birth. Most of the women (5021) included in the total figure of 6082 were participants in a, quasi-randomized trial published in 1942 (1). Comparative studies without random allocation of subjects were excluded. The trials were identified by electronic searches of the Cochrane Controlled Trials Register, MEDLINE and EMBASE, using standard methodology of the Cochrane Collaboration. Data analysis and reporting also followed standard Cochrane methods.

The main analysis suggests that the risk of pre-eclampsia is reduced when antioxidants are administered during pregnancy. Many pre-specified subgroup analyses are presented in the review according to women's risk status, trial quality, gestational age at entry, and dose level. All subgroup analyses are consistent with the main analysis, which further suggest that antioxidants may be a promising approach for the prevention of pre-eclampsia. Moreover, compared to controls, women receiving antioxidants also had a reduced risk of having a small-for-gestational-age infant (Relative risk [RR] 0.64, 95% confidence interval [CI] 0.47 to 0.87, three trials, 634 women). A negative finding, however, is the increased risk of preterm birth, which may partly explain the effect of the intervention (i.e. if gestation is shorter, the probability of a woman developing pre-eclampsia may be lower).

The review is unbiased and thorough. The data are clearly tabulated and graphically presented for overall findings and for different subgroups. The main conclusion—the absence of sufficient evidence of effectiveness—is supported by the data presented.

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