Combined Vitamin C and E Supplementation for the Prevention of Preeclampsia: A Systematic Review and Meta-Analysis

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To perform a systematic review and meta-analysis of the effectiveness of combined vitamin C and E (vitCE) supplementation for the prevention of preeclampsia.

Data Sources.

PubMED, Web of Science, and Cochrane Central Register of Controlled Trials from inception through June 2010, and bibliographies of review articles and eligible studies.

Methods of Study Selection.

Fifteen eligible studies that evaluated vitCE supplementation for the prevention of preeclampsia were identified. On the basis of prespecified inclusion and exclusion criteria, 9 were included in the meta-analysis. All were randomized controlled trials. The reporting and methodologic quality of the included studies was assessed with the CONSORT checklist and the Jadad scale.

Tabulation, Integration, and Results.

The 9 included studies had moderate-to-high CONSORT and Jadad scores. The incidence of preeclampsia was 9.7% (949 of 9833) in the vitCE group and 9.5% (946 of 9842) in the placebo group. A random effects model was used for pooling and no difference was found in the relative risk (RR) of preeclampsia between the vitCE and placebo groups (RR: 0.98; 95% confidence interval [CI]: 0.87–1.10). The incidence of gestational hypertension was 22.6% (1915 of 8491) in the vitCE group and 20.3% (1728 of 8500) in the placebo group (RR: 1.11, 95% CI: 1.05–1.17). The incidence of placental abruption was 0.58% (43 of 7379) in the vitCE group and 0.87% (64 of 7361) in the placebo group (RR: 0.67, 95% CI: 0.46–0.98). No significant differences were observed for other maternal and neonatal outcomes.


Combined VitCE supplementation does not decrease the risk of preeclampsia and should not be offered to gravidas for the prevention of preeclampsia or other pregnancy induced hypertensive disorders. Furthermore, combined supplementation with vitCE increased the risk of GH but decreased the risk of placental abruption. However, these latter associations may not be causal, especially since they were the product of multiple statistical comparisons, and the 95% CI around the point estimates almost included one.

Learning Objectives:

After completion of this educational activity, the obstetrician/gynecologist should be better able to assess the causes of preeclampsia and related conditions; evaluate and interpret the evidence regarding the use of combined vitamins C and E in prevention of preeclampsia and related conditions; and interpret and understand the effects of the supplementation of vitamins C and E for the prevention of preeclampsia or other pregnancy induced hypertensive disorders.

Target Audience:

Obstetricians & Gynecologists, Family Physicians

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