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Pre-eclampsia (PE) affects 2-8% of pregnancies and is responsible for significant morbidity and mortality. The maternal clinical syndrome (defined by hypertension, proteinuria, and organ dysfunction) is the result of endothelial dysfunction. The endothelial response to increased levels of soluble FMS-like Tyrosine Kinase 1 (sFLT1) is thought to play a central role. sFLT1 is released from multiple tissues and binds VEGF with high affinity and antagonizes VEGF. Expression of soluble variants of sFLT1 is a result of alternative splicing; however, the mechanism is incompletely understood. We hypothesize that neuro-oncological ventral antigen 2 (NOVA2) contributes to this. NOVA2 was inhibited in human umbilical vein endothelial cells (HUVECs) and multiple cellular functions were assessed. NOVA2 and FLT1 expression in the placenta of PE, pregnancy-induced hypertension, and normotensive controls was measured by RT-qPCR. Loss of NOVA2 in HUVECs resulted in significantly increased levels of sFLT1, but did not affect expression of membrane-bound FLT1. NOVA2 protein was shown to directly interact with FLT1 mRNA. Loss of NOVA2 was also accompanied by impaired endothelial functions such as sprouting. We were able to restore sprouting capacity by exogenous VEGF. We did not observe statistically significant regulation of NOVA2 or sFLT1 in the placenta. However, we observed a negative correlation between sFLT1 and NOVA2 expression levels. In conclusion, NOVA2 was found to regulate FLT1 splicing in the endothelium. Loss of NOVA2 resulted in impaired endothelial function, at least partially dependent on VEGF. In PE patients, we observed a negative correlation between NOVA2 and sFLT1., (© 2022. The Author(s).)

Objective: To describe the maternal and neonatal outcomes and prolongation of pregnancies with severe early onset pre-eclampsia before 26 weeks of gestation., Design: Nationwide case series., Setting: All Dutch tertiary perinatal care centres., Population: All women diagnosed with severe pre-eclampsia who delivered between 22 and 26 weeks of gestation in a tertiary perinatal care centre in the Netherlands, between 2008 and 2014., Methods: Women were identified through computerised hospital databases. Data were collected from medical records., Main Outcome Measures: Maternal complications [HELLP (haemolysis, elevated liver enzyme levels, and low platelet levels) syndrome, eclampsia, pulmonary oedema, cerebrovascular incidents, hepatic capsular rupture, placenta abruption, renal failure, and maternal death], neonatal survival and complications (intraventricular haemorrhage, retinopathy of prematurity, necrotising enterocolitis, bronchopulmonary dysplasia, and sepsis), and outcome of subsequent pregnancies (recurrent pre-eclampsia, premature delivery, and neonatal survival)., Results: We studied 133 women, delivering 140 children. Maternal complications occurred frequently (54%). Deterioration of HELLP syndrome during expectant care occurred in 48%, after 4 days. Median prolongation was 5 days (range: 0-25 days). Neonatal survival was poor (19%), and was worse (6.6%) if the mother was admitted before 24 weeks of gestation. Complications occurred frequently among survivors (84%). After active support, neonatal survival was comparable with the survival of spontaneous premature neonates (54%). Pre-eclampsia recurred in 31%, at a mean gestational age of 32 weeks and 6 days., Conclusions: Considering the limits of prolongation, women need to be counselled carefully, weighing the high risk for maternal complications versus limited neonatal survival and/or extreme prematurity and its sequelae. The positive prospects regarding maternal and neonatal outcome in future pregnancies can supplement counselling., Tweetable Abstract: Severe early onset pre-eclampsia comes with high maternal complication rates and poor neonatal survival., (© 2017 Royal College of Obstetricians and Gynaecologists.)

Objectives: Lifestyle interventions in obese pregnant women reduce adverse maternal outcomes of pregnancy. However, the association between weight change due to interventions and the actual reduction in complications is unknown. The objective of this study was to determine the association between gestational weight gain (GWG) and the rate of pregnancy complications., Study Design: The authors included randomized controlled trials (RCTs) assessing the effect of lifestyle interventions during pregnancy on GWG and adverse maternal and fetal outcomes. For each outcome they assessed the association between GWG and the risk of adverse pregnancy outcomes., Results: They analyzed data of 23 RCTs (4,990 women). Increased GWG was associated with a nonsignificant increase in the incidence of preeclampsia (PE) (0.2% per gained kg, 95% confidence interval [CI] 0.5 to 0.9%, p > 0.05), gestational diabetes (GDM) (0.3% per gained kg, 95% CI -0.5 to 1.0%, p > 0.05), and induction of labor (IOL) (1.5% per gained kg, 95% CI -0.9 to 3.9%, p > 0.05)., Conclusions: Reduction in GWG due to lifestyle interventions in pregnancy had statistically nonsignificant effects on lowering the incidence of PE, GDM, and IOL. Possibly, the beneficial effect of lifestyle interventions on pregnancy outcomes is due to an effect independent of the reduction of GWG., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The association between preeclampsia and cardiovascular disease has been an increasing area of interest over the last years. Cardiovascular disease is the number one cause of death in women in the western world and more women than men die of heart disease each year. The most common pregnancy disorder is preeclampsia. Preeclampsia is defined by hypertension and de novo proteinuria and remains responsible for high maternal and fetal morbidity and mortality worldwide. Pregnancy has been described as a "stress test" for future cardiovascular disease, to identify women young enough to benefit from screening. Women with a history of early onset (severe) preeclampsia have the highest risk of cardiovascular disease later. However, the exact underlying link between the two disorders is still unknown. In this review we describe different facets of the association between preeclampsia and cardiovascular disease and we give an overview of the recent literature.

Objective: To assess the economic consequences of labour induction compared with expectant monitoring in women with gestational hypertension or pre-eclampsia at term., Design: An economic analysis alongside the Hypertension and Pre-eclampsia Intervention Trial At Term (HYPITAT)., Setting: Obstetric departments of six university and 32 teaching and district hospitals in the Netherlands., Population: Women diagnosed with gestational hypertension or pre-eclampsia between 36(+0) and 41(+0) weeks of gestation, randomly allocated to either induction of labour or expectant monitoring., Methods: A trial-based cost-effectiveness analysis was performed from a societal perspective during a 1-year time horizon., Main Outcome Measures: One-year costs were estimated and health outcomes were expressed as the prevalence of poor maternal outcome defined as either maternal complications or progression to severe disease., Results: The average costs of induction of labour (n = 377) were €7077 versus €7908 for expectant monitoring (n = 379), with an average difference of -€831 (95% CI -€1561 to -€144). This 11% difference predominantly originated from the antepartum period: per woman costs were €1259 for induction versus €2700 for expectant monitoring. During delivery, more costs were generated following induction (€2190) compared with expectant monitoring (€1210). No substantial differences were found in the postpartum, follow-up and for non-medical costs., Conclusion: In women with gestational hypertension or mild pre-eclampsia at term, induction of labour is less costly than expectant monitoring because of differences in resource use in the antepartum period. As the trial already demonstrated that induction of labour results in less progression to severe disease without resulting in a higher caesarean section rate, both clinical and economic consequences are in favour of induction of labour in these women., Trial Registration: The trial has been registered in the clinical trial register as ISRCTN08132825., (© 2010 The Authors Journal compilation © RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology.)

Objective: To investigate differences in body composition and fat distribution between women with previous pre-eclampsia or small-for-gestational-age (SGA) offspring and those with uncomplicated pregnancies., Design: Cohort study., Setting: Population-based study in a genetically isolated population in the southwest of the Netherlands., Population: Women after pregnancies complicated by pre-eclampsia (n=45), SGA offspring (n=53) and uncomplicated pregnancies (n=106)., Methods: Women were compared for body composition and fat distribution variables, assessed by dual-energy X-ray absorptiometry (DXA) and anthropometrics at a mean follow-up time of 10.8 (SD +/- 5.9) years after pregnancy., Main Outcome Measures: Total lean and fat mass, android fat mass, gynoid fat mass, android-to-gynoid fat ratio, waist and hip circumference, waist-to-hip ratio., Results: Women with previous pre-eclampsia compared with controls had higher mean total fat mass index (11.5 +/- 0.6 versus 9.7 +/- 0.4 kg/m(2); P = 0.03), lean mass index (15.8 +/- 0.3 versus 14.5 +/- 0.2 kg/m(2); P =0.001) and body mass index ([BMI]; 28.4 +/- 0.8 versus 25.4 +/- 0.5 kg/m(2); P = 0.005). Their waist circumferences (90.7 +/- 2.0 versus 78.5 +/- 1.3 cm; P < 0.001) and waist-to-hip ratios (0.86 +/- 0.01 versus 0.77 +/- 0.01; P < 0.001) were also higher as well as android fat mass (2.8 +/- 0.2 versus 2.1 +/- 0.1 kg; P = 0.01) and android-to-gynoid fat ratios (0.45 +/- 0.02 versus 0.39 +/- 0.01; P = 0.02). Mean total fat, lean and BMI was not significantly different between women with previous SGA offspring and controls, yet waist-to-hip ratios (0.83 +/- 0.01; P < 0.001) were higher. The observed differences in waist and hip circumference, waist-to-hip ratio and gynoid fat mass could not be attributed to differences in BMI., Conclusion: Women with previous pre-eclampsia or SGA offspring pregnancies compared with those with uncomplicated pregnancies have a preferential fat accumulation in the abdominal over hip region, which may explain, at least partly, their increased cardiovascular risk.

The STOX1 gene, identified as a candidate gene for pre-eclampsia in Dutch women, is placentally expressed and subject to imprinting with preferential transmission of the maternal allele. In our study, STOX1-Y153H frequencies were similar in 157 women with pre-eclampsia (65%) and in 157 controls (64%) from the general Dutch population. In an isolated Dutch population, a distortion could not be demonstrated in the transmission of STOX1-Y153H variation from heterozygous mothers to offspring in 50 and 56 families with pregnancies complicated by pre-eclampsia or intrauterine growth restriction, respectively. Our findings do not confirm previous suggestions that STOX1 plays a major role in Dutch women with pre-eclampsia.

Although the aetiology of preeclampsia is unknown, there is substantial evidence that it finds its roots in abnormal placentation. Prerequisites for successful placentation include trophoblast invasion, degradation and remodelling of the uterine decidual extracellular matrix, and apoptosis without thrombosis. We tested this hypothesis by analysing the effect of functional polymorphisms in the genes coding for MMP9, MMP3 and annexin A5 on the risk of preeclampsia using a case-control design. In 163 women with preeclampsia and 163 controls we studied the association with polymorphisms in the MMP9 (-1562 C/T), MMP3 (-1612 5A/6A) and annexin A5 (-1 C/T) genes using logistic regression analysis. A lower prevalence of the rare T allele of the MMP9 (-1562 C/T) polymorphism in women with preeclampsia was found (odds ratio 0.48, 95% confidence interval 0.25-0.90). The distribution of the MMP3 (-1612 5A/6A) and annexin A5 (-1 C/T) gene polymorphisms were similar in cases and controls. Our results suggest that the MMP9-1562T allele is associated with a reduced risk of preeclampsia and therefore may protect against maladaptation of the spiral arteries and decreased decidual degradation. The elevated MMP9 concentrations reported to be associated with the -1562T allele might be essential for the development of an adequate maternal-fetal interface early in pregnancy by facilitating trophoblast apoptosis and degradation.

Recently, it has been proposed that abnormalities in coagulation and fibrinolysis contribute to the development of preeclampsia by increasing the thrombotic tendency. This hypothesis was tested in women who have had preeclampsia (cases) compared with matched controls. Polymorphisms in the thrombophilia genes [plasminogen activator inhibitor type 1 [PAI-1 -675(4G/5G)], thrombin activatable fibrinolysis inhibitor (TAFI -438G/A and 1040C/T), methylenetetrahydrofolate reductase (MTHFR 677C/T), factor V (FV Leiden R/Q506), prothrombin (FII 20210G/A) and factor XIIIA (FXIIIA V/L34)] were determined in 157 women with preeclampsia and 157 women with uncomplicated pregnancy. The associated risk of preeclampsia was analyzed using logistic regression methods. The frequency distributions of the genotypes of these six polymorphisms in thrombophilia genes were similar in the case and control groups. We found no differences in the prevalence of genetic risk factors of thrombosis in women with preeclampsia compared with controls, which makes it unlikely that these polymorphisms are risk factors for preeclampsia.

Recently, it has been described that human fertility is associated with the interleukin 10 (IL10) -2849 AA genotype. Pre-eclampsia is the most common pregnancy-specific complication. In the pathogenesis of pre-eclampsia, IL10 may affect maternal intravascular inflammation as well as endothelial dysfunction. Therefore, we tested the hypothesis that pre-eclampsia is associated with genetic variation in the IL10 promoter region in a case-control study for pre-eclampsia. Women homozygous for the IL10 -2849A allele have a threefold reduced risk for pre-eclampsia compared to controls (odds ratio 0.29; 95% CI 0.10-0.83). No differences in genotype frequency were found for polymorphisms in the IL10 promoter region at positions -1082, -819 and -592. This suggests that there is a genetically determined mechanism which protects the mother against pre-eclampsia, as reflected in the lower frequency of the IL10 -2849AA genotype in pre-eclamptic women.

Objectives: (1) To assess the recurrence rate of pre-eclampsia in women with this history before 34 weeks of pregnancy and thrombophilia. (2) To evaluate the effects of low-molecular-weight heparin (LMWH) on pregnancy outcome., Methods: In a multicentre retrospective study subsequent pregnancies of women with a history of pre-eclampsia necessitating birth before 34 weeks and thrombophilia were analysed. Of 58 women, 26 received LMWH and aspirin (ASA) and 32 ASA (22) or no (10) medication in their subsequent pregnancies., Results: In eight women treated with LMWH and ASA and in 16 women receiving ASA or no medication pre-eclampsia recurred in the subsequent pregnancy. (OR 0.55, 95% CI 0.15-1.31) There were no significant differences in birth weight or gestational age between both groups., Conclusions: The recurrence rate of pre-eclampsia in women with thrombophilic disorders is high in this small retrospective study. No positive effect was found for LMWH treatment. A multicentred randomised study has been started to reach an adequate number of patients to evaluate the influence of LMWH treatment.

Although the pathophysiology of pre-eclampsia is unknown, several studies have indicated that abnormal placentation early in pregnancy might play a key role. It has recently been suggested that this abnormal placentation may result in transfusion of fetal cells (feto-maternal transfusion) in women with pre-eclampsia. In the present study, fetal nucleated red blood cells were isolated from 20 women with pre-eclampsia and 20 controls using a very efficient magnetic activated cell sorting (MACS) protocol. The number of male cells was determined using two-color fluorescence in situ hybridization (FISH) for X and Y chromosomes. Significantly more XY cells could be detected in women with pre-eclampsia (0.61+/-1.2 XY cells/ml blood) compared to women with uncomplicated pregnancies (0.02+/-0.04 XY cells/ml blood) (Mann-Whitney U-test, p<0.001). These results suggest that fetal cell trafficking is enhanced in women with pre-eclampsia, and this finding may contribute to the understanding of the pathophysiology of the disease., (Copyright 2001 John Wiley & Sons, Ltd.)

Objective: Recently, it has been proposed that hereditary coagulation abnormalities leading to an increased venous thrombosis risk may play a role in the development of preeclampsia. We tested this hypothesis in women who have had preeclampsia compared with matched control subjects., Study Design: We conducted a case-control study of 163 women with preeclampsia during 1991-1996. Control subjects were matched for age and delivery date. Patients and control subjects were tested for the presence of factor V Leiden, prothrombin 20210A allele, protein C, protein S, and antithrombin deficiency. Logistic regression methods were used for data analysis., Results: The prevalence of these genetic risk factors was similar in the patient group (12.9%) and the control group (12.9%; odds ratio, 1.0; 95% confidence interval, 0.5-3.9). Unexpectedly, we found a high prevalence of factor V Leiden in the control group (9.2%)., Conclusion: We found no differences in the prevalence of genetic risk factors of thrombosis in women with preeclampsia compared with control subjects.

Eicosanoids play an important role in the pathogenesis of preeclampsia. The major eicosanoid metabolite reported to be secreted by endothelial cells, the vasodilator prostacyclin, is generally reduced in preeclampsia. By contrast, it was shown previously that prostacyclin secretion by cultured human umbilical vein endothelial (HUVE) cells is increased significantly after exposure to blood from preeclamptic women. In the current study, eicosanoid profiles in conditioned media from HUVE cells incubated with pregnancy plasma were analyzed by high-performance liquid chromatography, thin layer chromatography and quantitative radio- and enzyme immunoassays. More prostaglandin F2alpha, prostacyclin and 8-isoprostane were secreted after exposure to plasma from preeclamptic women than plasma from matched, normal pregnant patients. Predominant secretion of the vasoconstrictor prostaglandin F2alpha by HUVE cell cultures and a stimulatory effect of preeclampsia plasma on eicosanoid biosynthesis underscore the importance of bioactive lipids in the vasospasm associated with clinical preeclampsia.

During the past decade a new hypothesis has been formulated that explains many of the disparate findings associated with the pregnancy syndrome preeclampsia. With an increased awareness of the physiological significance of vascular endothelial cell function, the seemingly unrelated signs of hypertension, proteinuria, edema, and hypercoagulability have converged to provide clinical evidence of a unifying pathophysiological mechanism: systemic, maternal endothelial cell dysfunction. Investigators have attempted to test this hypothesis through two approaches. The first approach involves the identification of in vivo markers of vascular endothelial cell injury in women with clinically evident preeclampsia. The second approach focuses on the ability of circulating factors derived from the serum or plasma of patients afflicted with preeclampsia to perturb endothelial cell function in vitro. In this review we summarize the increasingly compelling evidence that maternal vascular endothelial cells are a critical target for toxic humoral activities that precipitate the multifaceted preeclampsia syndrome.

Objective: Reduced trophoblastic migration into the decidua during the first half of pregnancy is a fundamental abnormality in preeclampsia. CA 125 and insulin-like growth factor binding protein-1 are major endometrial proteins whose primary sources are decidual epithelial and stromal cells, respectively. We hypothesized that reduced trophoblastic invasion in pregnancies destined for preeclampsia would affect the maternal vascular deportation of these decidual proteins., Study Design: CA 125 and insulin-like growth factor binding protein-1 concentrations were analyzed by radioimmunoassays of plasma from preeclamptic and matched control patients in a longitudinal, nested case-control study., Results: CA 125 concentrations did not differ with respect to pregnancy outcome or trimester. Midtrimester plasma insulin-like growth factor binding protein-1 concentrations were significantly lower in women who later had preeclampsia compared with normal pregnant controls., Conclusion: These findings provide biochemical evidence that abnormalities of trophoblastic invasion affect the maternal vascular deportation of a decidual stromal protein. Lower circulating concentrations of insulin-like growth factor binding protein-1 in women destined to have preeclampsia were observed 12 to 26 weeks before the onset of clinical signs of this syndrome.

Objective: Our purpose was to compare plasma concentrations of type II phospholipase A2 in normal and preeclamptic pregnancies and to determine whether plasma from preeclamptic patients increases endothelial cell secretion of type II phospholipase A2., Study Design: We compared the plasma levels of type II phospholipase A2 in 23 patients with normal pregnancies and 25 patients with strictly defined preeclampsia. Plasma samples were collected throughout pregnancy and stored at -80 degrees C. Patients with preeclampsia were matched closely as possible with controls for maternal age, race, gestational age at blood sampling, and parity. Plasma levels of type II phospholipase A2 were measured by enzyme immunoassay. To investigate endothelial cell type II phospholipase A2 production, we measured levels of prostacyclin and type II phospholipase A2 in conditioned media from cultured human umbilical vein endothelial cells exposed to plasma from preeclamptic and normal pregnant patients., Results: The mean plasma type II phospholipase A2 level in the mild preeclampsia group (6.1 +/- 3.0 ng/ml, n = 6) was not different from that in control patients (6.0 +/- 3.2 ng/ml, n = 23). However, the mean type II phospholipase A2 level in patients with severe preeclampsia (19.9 +/- 12.3 ng/ml, n = 19) was significantly higher when compared with the other two groups (p < 0.001). Prostacyclin concentrations in conditioned media of endothelial cells exposed to plasma from patients with preeclampsia were elevated compared with cells incubated with control plasma (8.6 +/- 1.7 vs 4.0 +/- 5.0 ng/ml, p < 0.05). However, the concentration of type II phospholipase A2 in conditioned medium was not significantly different (1.6 +/- 0.3 vs. 1.8 +/- 1.0 ng/ml, p = 0.40)., Conclusions: Plasma concentrations of type II phospholipase A2 are elevated in preeclampsia and correlate well with the severity of disease. Plasma from preeclamptic women increased secretion of prostacyclin, but not type II phospholipase A2 by endothelial cells in culture.

Objective: We investigated differences in prostacyclin production by endothelial cells exposed to plasma from either preeclamptic women or normal pregnant women., Study Design: A case-control study of matched preeclamptic and normal pregnancies was used to compare prostacyclin synthesis by human umbilical vein endothelial cells incubated with pregnancy plasma for 24 hours. Prostacyclin concentrations in conditioned media were measured by radioimmunoassay of its stable metabolite (6-keto-prostaglandin F1 alpha). Human umbilical vein endothelial cell lysates were used to determine concentrations of the enzymes cyclooxygenase and prostacyclin synthase., Results: Prostacyclin production by human umbilical vein endothelial cells incubated with plasma from preeclamptic women was significantly greater than that by cells exposed to normal pregnancy plasma. Differences in prostacyclin production under the two experimental conditions could be explained neither by differences in enzyme mass nor activities of cyclooxygenase and prostacyclin synthase., Conclusion: The stimulatory effect of preeclampsia plasma on prostacyclin biosynthesis in human umbilical vein endothelial cells appears to be manifested at a step(s) proximal to the activation of cyclooxygenase. Possible mechanisms are increased phospholipase A2, lipoprotein, or lipid peroxide activities in preeclampsia.

Objective: Our purpose was to determine the presence and degree of endothelial injury, by measuring plasma concentrations of cellular fibronectin, in pregnancies complicated by preeclampsia or intrauterine growth retardation., Study Design: A matched, nested, case-control study design was used. Plasma was collected prospectively from pregnant women throughout gestation. At least 12 weeks after delivery women with preeclampsia, both preeclampsia and intrauterine growth retardation, or intrauterine growth retardation alone were identified. Normal controls were matched to these patients by age, race, and gestational age. Stored plasma, which had been obtained in the third trimester, was assayed for cellular fibronectin by means of a sensitive and specific enzyme immunoassay. After an appropriate transformation of the data results were compared with one-way analysis of variance with Fisher's post hoc test., Results: Patients with preeclampsia (n = 18) had higher plasma cellular fibronectin concentrations than did control patients (n = 68) with median values of 2.8 and 1.4 micrograms/ml, respectively (p < 0.001, using transformed data). Patients with intrauterine growth retardation alone (n = 10) had 2.3 micrograms/ml cellular fibronectin, significantly higher than values of controls (p < 0.02 using transformed data) and significantly lower than those of patients with preeclampsia (p < 0.05 using transformed data)., Conclusion: Pregnancies complicated by preeclampsia had significantly higher plasma cellular fibronectin concentrations than did pregnancies with intrauterine growth retardation alone, which in turn had significantly higher plasma cellular fibronectin concentrations than did control pregnancies. We speculate that endothelial involvement in intrauterine growth retardation is confined to the uteroplacental circulation, whereas it is systemic in preeclampsia.

Objective: Elevated growth factor activity in women with preeclampsia is caused by an acid- and heat-labile protein complex with a native molecular mass of 150,000. The major plasma insulin-like growth factor-binding protein-3 has identical molecular characteristics. We hypothesized that increased endothelial cell release or decreased proteolytic degradation of insulin-like growth factor-binding protein-3 in preeclampsia would result in higher circulating levels of insulin-like growth factors and hence in increased mitogenic activity., Study Design: Plasma insulin-like growth factor-binding protein-3 concentrations were determined by iodine-125 insulin-like growth factor-II radioligand blots of nonreducing gels in 16 normal and 16 preeclamptic patients collected from a prospective, case-control study. Enzyme-linked immunosorbent assays also were performed with a specific anti-insulin-like growth factor-binding protein-3 antiserum., Results: Insulin-like growth factor-binding protein-3 concentrations were not different between women with normal versus preeclamptic pregnancies (p = 0.23). Enzyme-linked immunosorbent assays confirmed these results in a subset of patients., Conclusions: The findings indicate that insulin-like growth factor-binding protein-3 concentrations do not account for the elevated mitogenic activity observed in plasma from women with preeclampsia and are not a useful screening test for preeclampsia risk.

Pre-eclampsia is a pregnancy-specific syndrome of unknown etiology, defined by clinical findings of elevated blood pressure combined with proteinuria and oedema. The decidual portion of the spiral arteries of women who later develop pre-eclampsia does not undergo the normal pregnancy-induced remodelling that converts these vessels to high volume-low resistance conduits. We have postulated that this failure leads to vascular spasm, restricted blood flow, placental ischaemia and the release of toxic substances that enter the maternal circulation, resulting in multi-organ disease. The complex and interwoven pathways of endocrine, paracrine and autocrine factors appear to result in a vicious cycle of endothelial cell dysfunction, which is expressed clinically as pre-eclampsia.

This prospective, nested, case-control study investigated whether maternal plasma fetal fibronectin reflects reduced trophoblastic invasion at 16 to 20 weeks in women who later have preeclampsia. Concentrations of fetal fibronectin were 8.7 +/- 2.6 micrograms/ml in women with preeclampsia and 8.1 +/- 2.5 micrograms/ml in matched controls (p greater than 0.5). These results are discussed.

Objective To investigate differences in body composition and fat distribution between women with previous pre-eclampsia or small-for-gestational-age (SGA) offspring and those with uncomplicated pregnancies. Design Cohort study. Setting Population-based study in a genetically isolated population in the southwest of the Netherlands. Population Women after pregnancies complicated by pre-eclampsia ( n=45), SGA offspring ( n=53) and uncomplicated pregnancies ( n=106). Methods Women were compared for body composition and fat distribution variables, assessed by dual-energy X-ray absorptiometry (DXA) and anthropometrics at a mean follow-up time of 10.8 (SD ±5.9) years after pregnancy. Main outcome measures Total lean and fat mass, android fat mass, gynoid fat mass, android-to-gynoid fat ratio, waist and hip circumference, waist-to-hip ratio. Results Women with previous pre-eclampsia compared with controls had higher mean total fat mass index (11.5 ± 0.6 versus 9.7 ± 0.4 kg/m2; P = 0.03), lean mass index (15.8 ± 0.3 versus 14.5 ± 0.2 kg/m2; P =0.001) and body mass index ([BMI]; 28.4 ± 0.8 versus 25.4 ± 0.5 kg/m2; P = 0.005). Their waist circumferences (90.7 ± 2.0 versus 78.5 ± 1.3 cm; P < 0.001) and waist-to-hip ratios (0.86 ± 0.01 versus 0.77 ± 0.01; P < 0.001) were also higher as well as android fat mass (2.8 ± 0.2 versus 2.1 ± 0.1 kg; P = 0.01) and android-to-gynoid fat ratios (0.45 ± 0.02 versus 0.39 ± 0.01; P = 0.02). Mean total fat, lean and BMI was not significantly different between women with previous SGA offspring and controls, yet waist-to-hip ratios (0.83 ± 0.01; P < 0.001) were higher. The observed differences in waist and hip circumference, waist-to-hip ratio and gynoid fat mass could not be attributed to differences in BMI. Conclusion Women with previous pre-eclampsia or SGA offspring pregnancies compared with those with uncomplicated pregnancies have a preferential fat accumulation in the abdominal over hip region, which may explain, at least partly, their increased cardiovascular risk. [ABSTRACT FROM AUTHOR]

The STOX1 gene, identified as a candidate gene for pre-eclampsia in Dutch women, is placentally expressed and subject to imprinting with preferential transmission of the maternal allele. In our study, STOX1-Y153H frequencies were similar in 157 women with pre-eclampsia (65%) and in 157 controls (64%) from the general Dutch population. In an isolated Dutch population, a distortion could not be demonstrated in the transmission of STOX1-Y153H variation from heterozygous mothers to offspring in 50 and 56 families with pregnancies complicated by pre-eclampsia or intrauterine growth restriction, respectively. Our findings do not confirm previous suggestions that STOX1 plays a major role in Dutch women with pre-eclampsia. [ABSTRACT FROM AUTHOR]