144

SCIENCE & PRACTICE

Pre-eclampsia:

than

pregnancy-induced
hypertension

more

and eclampsia are the most important

of maternal death in the USA, Scandinavia, Iceland,
Finland, and the UK.1-3 They occupy the same prime
position as they did nearly 40 years ago.4
Pre-eclampsia is not only common and dangerous for
both mother and baby, but also unpredictable in onset and
progression, and incurable except by termination of the
pregnancy. Because the pathogenesis is unclear there is no
specific diagnostic test; the disorder is recognised by the
concurrence of pregnancy-induced changes that regress
after delivery, of which hypertension and proteinuria are the
easiest to recognise and the signs by which the maternal
syndrome is defined.
Several classification schemes have been proposed to aid
clinical recognition of pre-eclampsia. The scheme
advocated by the US National Institutes of Health working
group on hypertension in pregnancy is outlined in table 1.5 It
emphasises, as do other similar classifications, the
distinction between a woman whose hypertension antedates
pregnancy and one with increased blood pressure as a sign of
pre-eclampsia. This classification helps greatly in
recognition of the patient with the disorder but has had the
of overemphasising
the
undesirable
consequence
importance of hypertension in the pathophysiology. As a
result, patients with other signs of pre-eclampsia but
without an increase in blood pressure may be mismanaged.
The recognition of the HELLP (haemolysis, elevated liver
enzyme activity, low platelets) variant of the disorder
emphasises how important it is to look at the whole
pathophysiological picture in diagnosing and managing
pre-eclampsia. Conversely, the emphasis on raised blood
pressure leads to the conclusion that all women whose blood
pressure increases during pregnancy have a single disorder.
Although appropriate for clinical management, this concept
has hindered understanding of the pathophysiology and
natural history of the disease. Epidemiological studies have
shown at least two forms of pregnancy-related
hypertension—pre-eclampsia, which increases fetal and
maternal mortality and morbidity but in which the

Pre-eclampsia

causes

cardiovascular abnormalities completely disappear aft

pregnancy, and transient hypertension, which predicts fix
hypertension in later life but has no acute consequenc
Unfortunately, research to find out the pathophysiologic
mechanisms of pre-eclampsia has been guided by strategi
useful in the understanding of hypertension. Thus, studi
have concentrated on measuring pressor agents a
mineralocorticoids and investigating renal pathophysiolog
Here we review the pathological and physiological chang
of pre-eclampsia that show that this syndrome is more th

pregnancy-induced hypertension.

Pathological changes
The

pathological changes present in women dying wi

eclampsia are listed in table 11. The widespread presence
haemorrhage and necrosis suggests reduced perfusi
rather than the gross vascular disruption that would
expected with mechanical damage from high blo
pressure. In the brain, the most frequent lesion is petechi
haemorrhage (perhaps agonal), and the subendocardi
necrosis found in this disorder is identical
hypovolaemic shock.6

to

that

seen

The

changes observed in renal and decidual vessels

with pre-eclampsia and eclampsia provide spec
insights. Electron-microscopic examination of renal biop
samples from pre-eclamptic women reveals changes seen
no other form of hypertension .7 The primary pathologi
change is in the glomerular capillary endothelial cells. T
cells are greatly increased in size, with electron-de
cytoplasmic inclusions that may occlude the capill
lumen. These changes support the idea that pre-eclampsi
a unique disease of pregnancy and direct attention
vascular endothelial damage in this disorder.
In normal pregnancy, as a result of trophoblastic invasi
there are striking changes in the arteries supplying
women

ADDRESSES:

Department of Obstetrics, Gynecology,

Reproductive Sciences, Magee Womens Hospital, Universit
Pittsburgh, Forbes Avenue, Pittsburgh, Pennsylvania 152
USA (Prof J. M. Roberts, MD); and Nuffield Department
Obstetrics and Gynaecology, John Radcliffe Hospital, Oxfo
UK (Prof C. W. G. Redman, FRCP). Correspondence to Prof James
Roberts.