Introduction
Pre-eclampsia aff ects 2–3% of all pregnancies, and every
year is responsible for about 60 000 deaths worldwide.1
In
the UK, hypertensive disease in pregnancy is a major cause
of maternal death.2
Pre-eclampsia is a syndrome in which
the placenta is implicated in the evolution of a generalised
maternal infl ammatory response, characterised by
activation of maternal vascular endothelial cells and
leucocytes.3,4 Markers of oxidative stress are present in the
placenta and maternal circulation of aff ected women,
suggesting it as a cause of the disorder. As such, antioxidants
might help to prevent pre-eclampsia, though this
notion has yet to be tested in large randomised trials.4,5
In 1999, we published the results of a small, randomised
controlled trial6
in which we assigned women at risk of
pre-eclampsia daily vitamin C (1000 mg) and vitamin E
(400 IU) from 16–22 weeks’ gestation. The primary
outcome was a reduction in maternal concentrations of
biomarkers of pre-eclampsia; the disorder itself was a
secondary outcome. The trial was stopped early after an
interim analysis showed a signifi cant improvement in
the primary outcome (plasminogen-activator inhibitor
[PAI]1-to-PAI-2 ratio); rate of pre-eclampsia was also
reduced. Women entered the trial mainly on the basis of
an abnormal uterine artery doppler waveform (a
recognised risk factor for pre-eclampsia). The fi ndings
of another, smaller study7
of women judged at risk of
pre-eclampsia on the basis of their clinical history
indicated no evidence of benefi t with the same