Pre-eclampsia is a pregnancy-related condition characterized by hypertension, proteinuria and endothelial dysfunction. VEGF165b, formed by alternative splicing of VEGF (vascular endothelial growth factor) pre-mRNA, inhibits VEGF165-mediated vasodilation and angiogenesis, but has not been quantified in pregnancy. ELISAs were used to measure means±S.E.M. plasma VEGF165b, sEng (soluble endoglin) and sFlt-1 (soluble fms-like tyrosine kinase-1). At 12 weeks of gestation, the plasma VEGF165b concentration was significantly up-regulated in plasma from women who maintained normal blood pressure throughout their pregnancy (normotensive group, 4.90±1.6 ng/ml; P<0.01, as determined using a Mann-Whitney U test) compared with non-pregnant women (0.40±0.22 ng/ml). In contrast, in patients who later developed pre-eclampsia, VEGF165b levels were lower than in the normotensive group (0.467±0.209 ng/ml), but were no greater than non-pregnant women. At term, plasma VEGF165b concentrations were greater than normal in both pre-eclamptic (3.75±2.24 ng/ml) and normotensive (10.58 ng/ml±3.74 ng/ml; P>0.1 compared with pre-eclampsia) pregnancies. Patients with a lower than median plasma VEGF165b at 12 weeks had elevated sFlt-1 and sEng pre-delivery. Concentrations of sFlt-1 (1.20±0.07 and 1.27±0.18 ng/ml) and sEng (4.4±0.18 and 4.1±0.5 ng/ml) were similar at 12 weeks of gestation in the normotensive and pre-eclamptic groups respectively. Plasma VEGF165b levels were elevated in pregnancy, but this increase is delayed in women that subsequently develop pre-eclampsia. In conclusion, low VEGF165b may therefore be a clinically useful first trimester plasma marker for increased risk of pre-eclampsia.

Objective Pre-eclampsia is diagnosed by hypertension and proteinuria, probably caused by endothelial dysfunction, resulting in symptoms including oedema, inflammation and altered metabolism. Vascular endothelial growth factor A (VEGF-A) is detected at higher concentrations in plasma from patients with pre-eclampsia than in plasma from normotensive pregnant patients when determined by radioimmunoassay. This study tested the hypothesis that circulating VEGF-A in pre-eclamptic plasma is biologically active in vivo, and aimed to identify specific isoforms responsible for this activity.Design Plasma from pre-eclamptic (n = 17) and normotensive (n = 10) pregnant women was perfused into Rana mesenteric microvessels, and the subsequent change in microvascular permeability was measured using a single-vessel perfusion microocclusion technique.Results Pre-eclamptic but not normotensive plasma resulted in a 5.25 ± 0.8-fold acute increase in vascular permeability (P = 0.0003). This increase could be blocked by the incubation of plasma with bevacizumab, an antibody to VEGF-A (n = 7; P = 0012), and by VEGF-A receptor inhibition by SU5416 at doses specific to VEGF-A receptor-1 (VEGFR1), but not by the VEGF-A receptor-2 inhibitor, ZM323881. Although VEGF 165 b levels were not significantly altered in the PET samples, the increase in permeability was also inhibited by incubation of preeclamptic plasma with an inhibitory monoclonal antibody specific for VEGF 165 b (n = 6; P < 0.01), or by the addition of placental growth factor 1 (PlGF-1; n = 3; P < 0.001). PlGF-1 was detected at lower concentrations in pre-eclamptic plasma than in normotensive plasma.Conclusions These findings suggest that circulating VEGF-A levels in pre-eclampsia are biologically active because of a loss of repression of VEGFR1 signalling by PlGF-1, and VEGF 165 b may be involved in the increased vascular permeability of preeclampsia.

The aim of this study was to determine the compliance rates for women being offered routine antenatal anti-D prophylaxis in two obstetric units in the UK. Haemolytic disease of the newborn (HDN) is a potentially serious condition that can result in substantial morbidity and sometimes death. Current guidelines recommend that 500 IU anti-D immunoglobulin G (IgG) should be offered to all non-sensitized RhD-negative women at 28 and 34 weeks' gestation in order to prevent the risk of RhD sensitization in pregnancy. Implementing guidance, however, remains a challenge. We conducted a retrospective audit of 207 RhD-negative, non-sensitized pregnant women attending obstetric units during 2004 to assess compliance with national guidance on the provision of antenatal anti-D prophylaxis. Informed consent for routine antenatal anti-D prophylaxis was documented for 185 of these women. In total, 86.5% of women received the two doses of anti-D IgG. The majority of women received their first and second doses within 1 week of 28 and 34 weeks' gestation (87.0 and 86.0%, respectively). Accurate records of prophylactic anti-D IgG were maintained and updated. This audit demonstrates that the level of patient compliance with the two-dose regimen was high.

A 73-year-old man presented with a huge intra-abdominal mass. Initially a gastrointestinal stromal tumour (GIST) was diagnosed, but his tumour was subsequently classified as a spindle cell sarcoma. Difficulties in the classification of rare intra-abdominal tumours are discussed.

There is a significant glycocalyx present at the maternal-fetal interface of the human placenta, with increasing evidence to suggest it has an important role in placental function. Glycocalyx is adversely affected by traditional tissue processing and fixation techniques. Using transmission electron microscopy, we present methodologies for reliably imaging and measuring glycocalyx of both the syncytiotrophoblast and fetal capillary endothelium in term healthy placentae. These techniques can be used to study the role of the placental glycocalyx in both health and disease, including pre-eclampsia. HIGHLIGHTS: • Glycocalyx is present at the maternal-fetal interface of the human placenta • A new method for the ultrastructural imaging of placental glycocalyx is presented • Visualisation of placental glycocalyx is enhanced by these methods • These techniques can be used to study the role of the placental glycocalyx

BackgroundPre-eclampsia remains a dominant cause of maternal and fetal mortality in developed countries. In a previous prospective study we identified a fall in the VEGF-A isoform VEGF-A165b in the plasma of patients in the first trimester to be a predictor of later pre-eclampsia. VEGF-A165b has been shown to have potent cytoprotective properties in many cell types. We therefore tested the hypothesis that VEGF-A165b may be cytoprotective for placental trophoblasts.MethodsWe used an immortalised first trimester trophoblast cell line exposed to chemical toxicity, and physiological (<2% O2) and atmospheric oxygen (21% O2) in the presence or absence of VEGF-A165b, angiogenic VEGF-A165a, a non-specific anti-VEGF-A blocking antibody (bevacizumab), or a specific anti-VEGF-A165b antibody. Cell viability and cytotoxicity were measured by trypan blue and LDH assay respectively.ResultsUnder high (21%) levels of oxygen, trophoblast viability was increased, and cytotoxicity reduced by exogenous recombinant VEGF-A165b (p < 0.05, n = 10) or VEGF-A165a. The cytoprotective effect was not seen under lower (<2%) oxygen conditions, where VEGF-A165b was upregulated. However inhibition of VEGF-A with blocking antibodies (bevacizumab or anti-VEGF-A165b) had marked cytotoxic effects under low oxygen conditions presumably through the blockade of autocrine survival pathways.ConclusionsThese results show that when trophoblasts are exposed to lower oxygen tensions (as they are early in the 1st trimester) endogenous VEGF-A165b contributes to their survival through an autocrine pathway. In contrast in high oxygen conditions exogenous VEGF-A isoforms have a greater effect on trophoblast survival.

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Since its discovery in 1997, the presence of cell-free fetal DNA in the maternal bloodstream has been put to clinical use to detect variety of fetal conditions, in the antenatal period. The use of fetal DNA can offer a highly accurate screen for the presence of Down syndrome (trisomy 21). This has numerous advantages over standard first trimester combined screening for Down syndrome; for example, a reduction in miscarriages due to its non-invasive nature. This article considers a number of issues that need to be resolved before widespread implication of this type of screening into standard NHS practice.