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


RESULTS
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.


CONCLUSIONS
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.


BACKGROUND
The Wellcome Trust.
McCance
David R
DR
Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, UK. david.mccance@belfasttrust.hscni.net
Holmes
Valerie A
VA
Maresh
Michael J A
MJ
Patterson
Christopher C
CC
Walker
James D
JD
Pearson
Donald W M
DW
Young
Ian S
IS
D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D005260:Female; D006801:Humans; D018384:Oxidative Stress; D011225:Pre-Eclampsia / Q000503:physiopathology / Q000517:prevention & control*; D011247:Pregnancy; D014810:Vitamin E / Q000627:therapeutic use*; D055815:Young Adult
D000975:Antioxidants; D014810:Vitamin E; D001205:Ascorbic Acid