It is clear that defects in spiral artery remodeling and trophoblast invasion, two related but separate processes, are

characteristic of hypertensive disorders of pregnancy and fetal growth restriction [5,6]. These processes result in
impaired placentation and placental ischemia, which are thought to be the primary events leading to placental release
of soluble factors that cause systemic endothelial dysfunction resulting in the preeclamptic phenotype
By comparison, in preeclampsia, cytotrophoblast cells infiltrate the decidual portion of the spiral arteries, but fail to
penetrate the myometrial segment [9,10]. The spiral arteries fail to develop into large, tortuous vascular channels
created by replacement of the musculoelastic wall with fibrinoid material; instead, the vessels remain narrow,
resulting in placental hypoperfusion
Plasma volume is reduced amongst women with pre-eclampsia (Comparison of total blood volume in normal,
preeclamptic, and nonproteinuric gestational hypertensive pregnancy by simultaneous measurement of red blood cell
and plasma volumes 1998). This association has led to the suggestion that expanding the plasma volume might
improve maternal and uteroplacental circulation, and so potentially improve outcome for both the woman and her
baby.
All of the clinical features of preeclampsia can be explained as clinical responses to generalized endothelial
dysfunction [76,77]. As an example,
1. Hypertension results from disturbed endothelial control of vascular tone
2. Proteinuria and edema are caused by increased vascular permeability
3. Coagulopathy is the result of abnormal endothelial expression of procoagulants
4. Headache, seizures, visual symptoms, epigastric pain, and fetal growth restriction are the sequelae of
endothelial dysfunction in the vasculature of target organs, such as the brain, liver, kidney, and placenta.
Plasma volume is reduced amongst women with pre-eclampsia, and this reduction is associated with a low
concentration of serum albumin (a type of protein). This association has led to the suggestion that, for women with
pre-eclampsia, expanding the plasma volume might improve maternal and uteroplacental circulation
Plasma volume expansion for treatment of pre-eclampsia (Cochrane Review 2000 3 trials involving total of 61
women)
The results of this review are inconclusive about the effects of plasma volume expansion for treatment of women with
pre-eclampsia. There is a strong argument that the use of plasma volume expansion, especially colloid solutions,
during pregnancy should be restricted to randomised trials.
Repeated albumin infusions do not lower blood pressure in preeclampsia - 1991
Since intravascular volume contraction is regarded as an important pathological feature in preeclampsia, it has
been proposed that plasma volume expansion could be a therapeutic manoeuver that interrupts the pathogenetic chain
of hypovolemia inducing increased vascular resistance. Furthermore, tissue perfusion should be improved and, if
albumin is used as plasma expander agent, interstitial edema should also be reduced. We report the results observed in
an open pilot study in ten preeclamptic patients treated with daily albumin infusions (0.4 to 1 g/kg) from 7 to 36 days.
No acute effects were shown on blood pressure, and the need for antihypertensive therapies did not decrease in
the following days. Serial evaluation after at least five or ten days of repeated albumin infusions did not show stable
changes in electrolytes excretion, renal clearances, serum protein concentration and hematocrit value, nor in
aldosterone, renin and atrial natriuretic peptide basal levels, while proteinuria tended to increase. Uteroplacental and
fetoplacental blood flow acutely ameliorated in 3 cases only after albumin 1 g/Kg, but reached basal values again on
the next day. The clinical implications are that daily albumin infusions with this schedule dosage do not lower
blood pressure and that they are unable to induce stable changes in renal function, uteroplacental and
fetoplacental resistance. No maternal complications were observed during the conservative management, but fetal
mortality was high (6/10). Given the uncontrolled study, we cannot know whether similar results had been achieved
by conventional therapy only.

In normal pregnancy the total body albumin mass increases, but the serum albumin concentrations and colloid
osmotic pressure decrease. Plasma volume and interstitial volume increase, and that capillary permeability is
unchanged. In pre-eclampsia the plasma volume contracts and there is an increased transcapillary escape rate of
Evans' blue with little change in the interstitial compartment volume [37]. Serum albumin concentrations and the
plasma colloid osmotic pressure are both reduced in severe pre-eclampsia, but vascular permeability, rather than renal
loss, has been suggested as the main determinant of this [38].
A randomised controlled trial comparing two temporising management strategies, one with and one without
plasma volume expansion, for severe and early onset pre-eclampsia. Ganzevoort 2005
OBJECTIVES: Plasma volume expansion may benefit both mother and child in the temporising management of
severe and early onset hypertensive disorders of pregnancy.
DESIGN: Randomised clinical trial. Setting Two university hospitals in Amsterdam, The Netherlands.
POPULATION: Two hundred and sixteen patients with a gestational age between 24 and 34 completed weeks with
severe pre-eclampsia, haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome or severe fetal growth
restriction (FGR) with pregnancy-induced hypertension, admitted between 1 April 2000 and 31 May 2003.
METHODS: One hundred and eleven patients were randomly allocated to the treatment group, (plasma volume
expansion and a diastolic BP target of 85-95 mmHg) and 105 to the control group (intravenous fluid restriction and
BP target of 95-105 mmHg). In the treatment group, a dose of 250 mL hydroxyethylstarch (HES) 6% (200/0.5)
was given twice daily over 4 hours.
MAIN OUTCOME MEASURES: Neonatal neurological development at term age (Prechtl score), perinatal death,
neonatal morbidity and maternal morbidity.
RESULTS: Baseline characteristics were comparable between groups. The median gestational age was 30 weeks. In
the treatment group, patients received higher amounts of intravenous fluids (median 813 mL/day vs 14 mL/day; P <
0.001) with a concomitant decreased haemoglobin count (median -0.6 vs-0.2 mmol/L; P < 0.001). Neither
neurological scores nor composite neonatal morbidity differed. A trend towards less prolongation of pregnancy
(median 7.4 vs 11.5 days; P= 0.054) and more infants requiring oxygen treatment >21% (66 vs 46; P= 0.09) in the
treatment group was observed. There was no difference in major maternal morbidity (total 11%), but there were
more caesarean sections in the treatment group (98%vs 90%; P < 0.05).
CONCLUSION: The addition of plasma volume expansion in temporising treatment does not improve maternal
or fetal outcome in women with early preterm hypertensive complications of pregnancy.