Fetal blood grouping using cell free DNA - an improved service for RhD negative pregnant women.

Red cell alloimmunisation involves the transplacental movement of maternally derived red cell antibodies into the fetal circulation, causing red cell haemolysis, fetal anaemia and ultimately fetal death. Current standard UK practice is to prevent sensitisation to the D antigen by administering anti-D at about 28 weeks' gestation to all RhD negative pregnancies. The determination of fetal blood group by non-invasive cell free fetal DNA testing offers an improved and more efficient service to RhD negative pregnant women and avoids the potential iatrogenic harm associated with standard practice. It also has significantly improved the management of women with red cell alloimunisation to D and other antigens. This review summarises the past and future management of red cell alloimmunisation during pregnancy and the impact of ffDNA tests.

Impaired vascular permeability regulation caused by the VEGF165b splice variant in 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 micro-occlusion 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 pre-eclamptic plasma with an inhibitory monoclonal antibody specific for VEGF165b (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 VEGF165b may be involved in the increased vascular permeability of pre-eclampsia.