Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT): a randomised placebo-controlled trial

Abstract

Background: Results of several trials of antioxidant use during pregnancy have not shown a reduction in pre-eclampsia, but the effect in women with diabetes is unknown. We aimed to assess whether supplementation with vitamins C and E reduced incidence of pre-eclampsia in women with type 1 diabetes.

Methods: We enrolled women from 25 UK antenatal metabolic clinics in a multicentre randomised placebo-controlled trial. Eligibility criteria were type 1 diabetes preceding pregnancy, presentation between 8 weeks' and 22 weeks' gestation, singleton pregnancy, and age 16 years or older. Women were randomly allocated in a 1:1 ratio to receive 1000 mg vitamin C and 400 IU vitamin E (alpha-tocopherol) or matched placebo daily until delivery. The randomisation sequence was stratified by centre with balanced blocks of eight patients. All trial personnel and participants were masked to treatment allocation. The primary endpoint was pre-eclampsia, which we defined as gestational hypertension with proteinuria. Analysis was by modified intention to treat. This study is registered, ISRCTN27214045.

Findings: Between April, 2003, and June, 2008, 762 women were randomly allocated to treatment groups (379 vitamin supplementation, 383 placebo). The primary endpoint was assessed for 375 women allocated to receive vitamins, and 374 allocated to placebo. Rates of pre-eclampsia did not differ between vitamin (15%, n=57) and placebo (19%, 70) groups (risk ratio 0.81, 95% CI 0.59-1.12). No adverse maternal or neonatal outcomes were reported.

Interpretation: Supplementation with vitamins C and E did not reduce risk of pre-eclampsia in women with type 1 diabetes. However, the possibility that vitamin supplementation might be beneficial in women with a low antioxidant status at baseline needs further testing.

Funding: The Wellcome Trust.

Figure 1

Trial profile

Figure 2

PAI-1 to PAI-2 ratio by weeks' gestation PAI-1 to PAI-2 ratio in vitamin and placebo groups at baseline, 26 weeks', and 34 weeks' gestation (within 2 weeks). Boxes show IQRs, and medians are shown by horizontal lines. Vertical lines extend to the highest and lowest values, but outliers (results exceeding the upper quartile by more than 1·5 times the IQR) are identified as individual symbols. Values greater than 5 are shown by arrows at the top of the figure. PAI=plasminogen activator inhibitor.

Figure 3

Plasma ascorbate and serum α-tocopherol concentrations, by weeks' gestation Mean plasma ascorbate (A) and serum α-tocopherol (B) concentrations in vitamin and placebo groups at baseline, 26 weeks', and 34 weeks' gestation (within 2 weeks). Error bars show 95% CIs.