Preeclampsia is a common and well-recognised complication of human pregnancy. It remains one of the main causes of maternal and fetal mortality and morbidity worldwide and no single cause has been identified, though there are many known risk factors. It is a multi-system disorder that affects the vascular endothelium and appears to originate from the placenta. No treatment exists, save the delivery of the fetus and placenta. There is no single diagnostic test for preeclampsia and it remains a clinical diagnosis only. A reliable diagnostic or predictive test could lead to new treatments and this would be of great clinical benefit as it would allow both more effective antenatal surveillance of high-risk pregnancies and also facilitate further research into the aetiology and treatment of preeclampsia. Previously published work has indicated a potential link between preeclampsia and IPGs. The nature of Inositol Phosphoglycans (IPGs) and their involvement (actual and theorised) in several pathologies is described. Pilot clinical data is presented to evaluate the utility of an ELISA assay for IPG-P in the screening and diagnosis of preeclampsia. The assay demonstrates a correlation between IPG-P levels in maternal urine and amniotic fluid in normal women but not in preeclampsia. The levels in preeclamptic women suggest a correlation with clinical severity of the disease. A hypothesis is presented suggesting disruption of maternal-fetal equilibrium in the preeclamptic disease state. Total IPG-P bioactivity assays of serum samples show no difference between preeclamptic and normal women, and it may therefore play no role in the condition. Alternatively, there is the possibility that a sub-fraction or an unidentified, abnormal IPG-P form is part of the process. Additionally, the ELISA assay demonstrates increased urinary IPG-P levels in normotensive labouring women. A second hypothesis is presented to suggest potential links between the onset of normal labour and the pathophysiology of preeclampsia. Finally, proposals for further work are discussed.

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Normal pregnancy was compared to preeclamptic (PE) pregnancy with respect to glomerular ultrafiltration nitric oxide (NO) activity, derived from the metabolism of L-arginine (L-arg) to citrulline. Two biomathematical models, the "isoporous plus shunt" (mean pore size ro, shunt component wo) and "lognormal" (mean pore size U, standard deviation S), together with fractional dextran clearance (betaD) enabled estimation of glomerular ultrafiltration parameters (Kf~ ultrafiltration coefficient, DP-transglomerular pressure). NO activity was assed from plasma and 24hr urinary NOx (nitrate and nitrite), second messenger cyclic GMP (cGMP) and NO synthase inhibitor asymmetric-D-methyl-arginine 9ADMA). Late pregnant (LP) and post partum (PP) data are presented. As NO might mediate gestational renal vasodilatation, the effects of infused L-arginine (NO precursor) compared to glycine, on ultrafiltration were examined, testing the hypothesis that NO deficiency is important in renal vasoconstriction and hypofiltration of PE.;Normal pregnancy is associated with increased GFR, ERPF, wo and S (p<0.05). PE pregnancy is associated with reduced Kf but increased ro, wo U and S. PE values PP approach controls. From the indices that were utilised, there was no evidence of significant NO deficiency in Preeclampsia and even if there was a relative deficiency the infusion of the NO precursor L-arginine failed to augment the decreased renal haemodynamics of Preeclampsia. In PE the hypofiltration therefore has both a haemodynamic and a structural basis, it recovers PP and L-arg has no ameliorating effect in LP, or PP.

Pre-eclampsia (PE) is a pregnancy specific condition that affects 2-3% of women. At present the cause of PE is unknown, however the main pathological features are impaired placentation, with inadequate invasion of the spiral arteries by syncytiotrophoblasts, and systemic endothelial damage, contributing to increased perinatal and maternal morbidity and mortality. PE may have life time consequences for the fetus in terms of greater predisposition to adult cardiovascular disease.

Preeclampsia (PE) is the commonest hypertensive disorder seen in pregnancy and is a significant cause for maternal mortality and morbidity world wide. Its impact on perinatal morbidity and mortality is difficult to measure. It is a well known fact that women who develop PE are at an increased risk of essential hypertension and other cardiovascular mortality like stroke and heart attacks. Recent literature has suggested that women who develop PE have increased markers of cardiovascular disease at the time of booking their pregnancy. We have previously demonstrated that reduction in capillary density after venous congestion (Structural capillary rarefaction) is an early marker for essential hypertension. We hypothesized that structural capillary rarefaction could be an early marker for PE. We aim to measure capillary density in primigravid Caucasian women with no other complications (low risk group) and in women with previous PE and Essential hypertension (high risk group). We measured fasting blood sugar, fasting insulin, fasting lipid profile at booking, VEGFR2 (angiogenic), sFlt-1 (antiangiogenic) and Endoglin (anti-angiogenic) factors along with their routine blood tests (11-16 weeks, 27-32 weeks, 34-38 weeks). Our objective was to find if capillary rarefaction existed before the onset of PE and if acted as a mediator of this syndrome, if so could it be used to predict PE either as a stand alone marker or in combination with other known predictive factors measured in this study. We recruited 326 subjects to participate in the study to measure capillary density at 11-16 weeks, 20-24 weeks, 28-31 weeks, 34-38 weeks and 5-15 weeks postnatally. After 150 women were followed up for all 5 visit and a normogram of capillary density changes in pregnancy was established, we selectively followed up women who had a uterine artery pulsatality index of < 2.5 at 21 weeks scan as they were low risk of developing PE. 15 women were lost for follow up and 5women were excluded because of violation of the protocol. 1 pregnancy was terminated for a foetal anomaly. A total of 305 women were analyzed. At the initial analysis it was found that capillary rarefaction occurred at 20 weeks in women who later developed preeclampsia. We measured VEGFR2 an endothelial progenitor cell marker involved in neoangiogenesis of capillaries. We also measured anti-angiogenic factors sFlt-1 and Endoglin in a cohort of women in the normotensive group at random and all the samples in the PE group. We found that capillary density at baseline and after venous congestion decreases as pregnancy progresses in normal pregnancy. In women who develop Preeclampsia the magnitude of decrease in capillary density at baseline and after venous congestion is exaggerated and is earlier compared to women who remained normotensive. The changes in anti-angiogenic factors are also exaggerated when compared to normal pregnancy. The VEGFR2 levels are lower at 34-38 weeks visit in women who had term preeclampsia when compared to normotensive women. Structural rarefaction of skin capillaries at 20-24 weeks gestation and 27-32 weeks gestation were reliable predictors of preeclampsia. Combining capillary rarefaction with uterine artery doppler pulsatility index can further increase the sensitivity and specificity of the prediction. We also confirmed that previous history of preeclampsia or chronic hypertension and high UAD pulsatility index were independent predictors of preeclampsia.

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