This study aimed to identify if the clinical features of proteinuric pre-eclampsia or the biochemical markers of endothelial dysfunction associated with this syndrome are altered according to parity in a direction that would suggest a different pathophysiology. Groups of 27 primigravid and 35 multigravid women with pre-eclampsia (defined as blood pressure > 140/90 mmHg and 2+ proteinuria) were studied ante-partum, and at 6 weeks and 6 months post-partum. Clinical markers of severity of pre-eclampsia, including blood pressure, markers of renal, hepatic and coagulatory function, and biochemical markers of endothelial dysfunction were measured. Fetal outcome was assessed by birthweight and birthweight percentile. Ante-partum systolic blood pressure was 10 mmHg higher in the primigravida, and this difference was independent of age and anti-hypertensive medication. Analysis of systolic blood pressure before and after delivery showed the primigravid women to have elevated systolic blood pressure over the whole time period ( P < 0.01). The primigravid women had more severe hepatic dysfunction, with elevated aspartate aminotransferase levels, but plasma creatinine, proteinuria, platelet counts and haematocrit were similar, indicating that renal and coagulatory function and plasma volume were affected to the same extent in the two groups and were independent of parity. Birthweight was similar in the two groups, and the percentage of infants weighing less than the 10th centile for gestation was also similar. Biochemical markers of endothelial dysfunction, assessed by measuring the urinary prostacyclin metabolite 2,3-dinor-6-oxo-prostaglandin F 1α and plasma endothelin 1, did not differ according to parity. There were no differences in a number of other biochemical markers of pre-eclampsia, including plasma albumin, uric acid, triacylglycerol, and total, low-density lipoprotein and high-density lipoprotein cholesterol. Basophil, monocyte and lymphocyte counts were elevated before delivery in primigravid women with pre-eclampsia. The differences in lymphocyte counts persisted post-partum. Further studies are required to clarify the role, if any, of monocytes, basophils and lymphocytes in the pathophysiology of pre-eclampsia. In conclusion, the elevated systolic blood pressure and raised aspartate aminotransferase levels observed in primigravida suggest a more severe form of pre-eclampsia. The lack of differences in birthweight and other biochemical and endothelial markers of severity of pre-eclampsia do not suggest a different pathophysiology; however, the persistently higher white cell counts in the primigravid pre-eclamptics are of interest, and might reflect differences in immune responses in the two groups. We suggest that studies of the pathophysiology of pre-eclampsia should include multigravida, as long as there is adequate post-partum follow-up to exclude underlying disease.

1. This study was designed to seek evidence for excessive lipid peroxidation in pre-eclamptic women using 8-iso-prostane as a novel bioactive marker of lipid peroxidation in vivo. Plasma free, total and urinary 8-iso-prostane were measured in 20 women with proteinuric pre-eclampsia, and compared with 18 age- and gestation-matched pregnant control subjects, before delivery and at 6 weeks postpartum. 2. Plasma free 8-iso-prostane was significantly elevated in the pre-eclamptic women compared with control subjects before delivery, and fell to control levels post-partum. Conversely, levels in women with normal pregnancy rose post-partum 3. Total plasma 8-iso-prostane levels were not significantly elevated in pre-eclamptic women compared with control subjects during pregnancy, but fell significantly in the pre-eclamptic women postpartum, suggesting that they had relatively higher levels compared with their non-pregnant state. 4. Urinary 8-iso-prostane excretion was significantly lower in the pre-eclamptic women compared with control subjects during pregnancy, suggesting that renal clearance of 8-iso-prostane is impaired in pre-eclampsia. 5. Increased levels of plasma free 8-iso-prostane in pre-eclampsia could be due to an increase in lipid peroxidation, an increase in phospholipase A 2 activity or a reduction in renal clearance of 8-iso-prostane, or a combination of all three. The potent direct and indirect vasoconstrictor actions of 8-iso-prostane may contribute to the pathogenesis of pre-eclampsia.