Maternal and fetal outcomes following unplanned conversion to general anesthetic at elective cesarean section.

OBJECTIVE: To investigate risk factors predicting unplanned conversion to general anesthesia during elective cesarean section, and to examine maternal and fetal outcomes associated with unplanned conversion compared with other modes of anesthesia. STUDY DESIGN: A retrospective cohort at a UK center (2008 to 2013). Women (4337) underwent elective cesarean section. Delivery outcomes were compared according to anesthesia type using logistic regression. RESULT: Women (1.6%) underwent unplanned conversion to general anesthetic. Unplanned conversion was associated with higher parity (odds ratio (OR) 3.82, confidence interval (CI; (1.58 to 9.62)) and maternal age ⩾40 (OR 4.40, CI (1.08 to 29.88)). Compared with spinal anesthetic, unplanned conversion was associated with increased likelihood of maternal hemorrhage ⩾1.5 l (OR 5.74, CI (1.90 to 14.01)) and delayed neonatal respiration (OR 4.76, CI (1.76 to 11.05)). Adverse outcomes were not significantly more likely compared with planned general anesthetic. CONCLUSION: Higher parity and maternal age are risk factors for unplanned conversion to general anesthetic. There is no increase in the likelihood of adverse outcomes with unplanned versus planned general anesthetic.

Accuracy of nuchal translucency measurement depends on equipment used and its calibration.

OBJECTIVES: To determine the effect of different ultrasound machine-probe combinations on nuchal translucency (NT) measurements and to assess how this impacts on the accuracy of the NT-derived component of first-trimester screening for trisomy 21. METHODS: Sixteen different ultrasound machine-probe combinations were used for axial measurement of 2.0-, 3.0- and 4.0-mm spaced targets in an ultrasound phantom. Differences between the measured and known values were determined. The mean of the axial measurements was used to calculate adjusted risks for trisomy 21, given specific clinical scenarios. RESULTS: Differences observed using different machine-probe combinations for the 2.0-mm target ranged from 1.8-2.2 mm; for the 3.0-mm target, 2.7-3.2 mm; and for the 4-mm target, 3.7-4.3 mm, and exceeded those due to intraobserver variability. For a fetal crown-rump length of 50.0 mm and NT measurement of 2.0 mm, the maximum/minimum measurements in the fetus of a 40-year-old woman led to derived risks ranging from 1 in 32 (NT, 2.2 mm) to 1 in 189 (NT, 1.8 mm) and in the fetus of a 20-year-old with an NT of 3.0 mm these ranged from 1 in 102 (NT, 3.2 mm) to 1 in 160 (NT, 2.7 mm). CONCLUSIONS: We have described the effect of machine-probe combinations on small but very precise ultrasound measurements. Such machine-probe combinations led to greater variability than those ascribed to intraobserver differences, and significantly affected the screening risk for the same fixed measurement. This finding has implications for Down syndrome screening algorithms and audit of ultrasound operators. Furthermore, most ultrasound machines are neither calibrated nor specified for measurements of tenths of a mm.

The impact of national guidance for anomaly screening and invasive testing: unintended consequences.

Recent guidance from the UK National Screening Committee (NSC) and the Fetal Anomaly Screening Programme (FASP) has led to important changes in prenatal ultrasound diagnosis and invasive testing. These relate to prenatal ultrasound investigation of what were previously known as 'soft markers' for Down's syndrome at the time of the detailed anomaly scan and as to whether full karyotype or FISH (fluorescent in situ hybridisation)/QFPCR (quantitative fluorescence PCR) testing for trisomies should be carried out when an invasive test is performed. Neither recommendation is directly related to the other but both in combination could have profound implications for the detection of chromosomal abnormalities other than trisomy 21 (Down's syndrome). In the light of two cases recently managed in one regional fetal medicine unit, we retrospectively reviewed cases where, with correct application of the NSC and FASP recommendations, non-lethal and clinically important chromosomal abnormalities would most likely not have been detected.

Vasoactive and permeability effects of vascular endothelial growth factor-165 in the term in vitro dually perfused human placental lobule.

Vascular endothelial growth factor (VEGF) is an important vasodilator and effector of permeability in systemic blood vessels. Molecular and tissue culture techniques have provided evidence for its placental synthesis and release. Using an in vitro dual-perfusion model of the term placental lobule from normal pregnancy, we report here the relative secretion of total VEGF, soluble VEGF receptor (VEGFR)-1, and free VEGF into the maternal and fetoplacental circulations of the placenta. We tested the hypothesis that VEGF has vasomotor and permeability effects in the fetoplacental circulation of the human placenta, and we examined the broad intracellular pathways involved in the vasodilatory effect that we found. We show that total VEGF is released into the fetal and maternal circulations in a bipolar fashion, with a bias toward maternal side output. Soluble VEGFR-1 was also secreted into both circulations with bias toward the maternal side. Consequently, free VEGF (12.8 +/- 2.4 pg/ml, mean +/- se) was found only in the fetoplacental circulation. VEGF-165 was found to be a potent vasodilator of the fetoplacental circulation (maximum response: 77% of previous steady-state fetal-side inflow hydrostatic pressure after preconstriction with U46619; EC(50) = 71 pm). This vasodilatory effect was mediated by the VEGFR-2 receptor and nitric oxide in a manner-independent of the involvement of prostacyclin and the src-family tyrosine kinases. However, nitric oxide could explain only 50% of the vasodilatory effect. Finally, we measured the permeability of the perfused placenta to inert hydrophilic tracers and found no difference in the presence and absence of VEGF.

The effects of vascular endothelial growth factor on endothelial cells: a potential role in preeclampsia.

OBJECTIVES: Preeclampsia is primarily a disorder of the maternal endothelium. An as yet unidentified circulating factor causes widespread alteration in endothelial function, and levels of vascular endothelial growth factor are elevated in preeclampsia. We hypothesized that vascular endothelial growth factor is involved in the alteration of endothelial function and set out to find further evidence for this contention. STUDY DESIGN: Bovine microvascular endothelial cells (B-88) were cultured in vitro. These cultured cells were then stimulated with vascular endothelial growth factor and with plasma from women with preeclampsia in the presence and absence of anti-vascular endothelial growth factor antibody. Prostacyclin, nitric oxide, and lactate dehydrogenase levels were measured. RESULTS: Vascular endothelial growth factor induced a significant concentration-dependent increase in prostacyclin production but not nitric oxide production. Cells stimulated with plasma from women with preeclampsia showed increases in production of both prostacyclin and nitric oxide. Vascular endothelial growth factor concentration in plasma was correlated with prostacyclin production by stimulated cells. The increase in prostacyclin production that usually followed the addition of plasma did not occur when anti-vascular endothelial growth factor antibody was present. CONCLUSIONS: Vascular endothelial growth factor has the ability to alter endothelial cell function in a manner analogous to that of plasma from women with preeclampsia.

Plasma from women with pre-eclampsia induces an in vitro alteration in the endothelium-dependent behaviour of myometrial resistance arteries.

OBJECTIVE: To compare the in vitro effect of plasma from normal pregnant women and women with pre-eclampsia on the endothelium-dependent behaviour of myometrial resistance arteries from normal pregnant women. DESIGN: An in vitro comparative study. SETTING: Nottingham City Hospital. SAMPLE: Uterine biopsy specimens were obtained from normal pregnant women delivered by elective caesarean section at term. Plasma was collected from nulliparous women with pre-eclampsia (n = 18), and from multiparous normal pregnant women (n = 18), all samples being matched for maternal age and gestation at venepuncture. Pools of plasma from women with pre-eclampsia and normal pregnant women were formed from these samples and were used in all the experiments. METHODS: Myometrial resistance vessels obtained from the uterine biopsies were incubated with normal pregnant plasma, plasma from women with pre-eclampsia, or without plasma. Wire myography was employed to study the effect of plasma on the endothelium-dependent behaviour of these vessels. RESULTS: Incubation of vessels from normal pregnant women with plasma from women with pre-eclampsia resulted in a significant reduction in endothelium-dependent relaxation, compared with vessels incubated either with plasma from normal pregnant women or without plasma. This alteration in endothelial function occurred after an incubation period of one hour and required a threshold concentration for its effect to become established. Removal of the vascular endothelium abolished these changes in vessel behaviour. There were no plasma-induced alterations in the endothelium-independent behaviour of the vascular smooth muscle. CONCLUSIONS: This study supports the hypothesis that plasma from women with pre-eclampsia is capable of altering endothelium-dependent myometrial relaxation in vessels from pregnant women.

VEGF via VEGF receptor-1 (Flt-1) mimics preeclamptic plasma in inhibiting uterine blood vessel relaxation in pregnancy: implications in the pathogenesis of preeclampsia.

Preeclampsia is a multisystem disorder characterized by hypertension and proteinuria. There is accumulating evidence that this is a disease of the endothelium, with an as-yet unidentified circulating factor, or factors, causing the observed alteration in vascular function. We previously reported that the function of myometrial vessels is altered on exposure to plasma from women with preeclampsia. Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that acts via two high-affinity receptors (KDR and Flt-1), and its production is increased in preeclampsia. Here we report that VEGF and its Flt-1 receptor may play a pivotal role in the altered vascular function of preeclampsia. Myometrial resistance vessels were obtained at the time of cesarean section. Using the Mulvany wire myograph, the endothelium-dependent behavior of these vessels was studied. Incubation of vessels from pregnant women with VEGF resulted in a reduction of endothelium-dependent relaxation that mimicked the reduction induced by plasma from women with preeclampsia. The altered function that occurred upon exposure of vessels to VEGF or plasma from women with preeclampsia did not occur when plasma was incubated with antibodies to VEGF before vessel incubation. The presence of an anti-KDR receptor antibody had no effect on VEGF response. However, in the presence of an anti-Flt-1 receptor antibody, VEGF or plasma from women with preeclampsia no longer attenuated the endothelium-dependent relaxation (p < 0.05). The changes observed with VEGF and plasma from women with preeclampsia and their subsequent blockade with anti-VEGF antibody and anti-Flt-1 receptor antibody strongly suggest that VEGF acting through the Flt-1 receptor is pivotal in the pathogenesis of this disease.

Preeclampsia: the endothelium, circulating factor(s) and vascular endothelial growth factor.

It has been proposed that endothelial cell activation is the primary event in the multisystem disorder of preeclampsia. Evidence for endothelial involvement in this condition abounds. The best-characterized morphologic abnormality of this syndrome, glomerular endotheliosis, involves endothelial cells. Also associated with preeclampsia is a loss of endothelial cell integrity, with the consequent increase in vascular permeability, and an increase in the circulating levels of the endothelial cell markers, fibronectin, von Willebrand factor, tissue plasminogen activator, and plasminogen activator inhibitor-1. It is now well documented that endothelial activation contributes to the coagulation abnormalities observed in this disease. There is much evidence that the endothelial alterations in preeclampsia result from one or more circulating factors. The incubation of cultured endothelial cells with serum or plasma samples, taken from normal pregnant women and women with preeclampsia, results in marked alterations in cell behavior and metabolic processes. More recently, experiments employing myographic techniques have demonstrated convincingly the effects of a circulating factor(s) on the function of endothelial cells of resistance arteries. Vascular endothelial growth factor (VEGF) possesses many of the characteristics required of a candidate circulating factor. It contains a hydrophobic secretory signal sequence, exerts in vitro effects specific to vascular endothelial cell, and promotes endothelial expression of procoagulant activity. Circulating VEGF concentrations are elevated in women with preeclampsia, and VEGF increases microvascular endothelial cell prostacyclin production in a dose-dependent manner, analogous to the acute effects of plasma from patients with preeclampsia. Similarly, in myographic studies, when myometrial resistance arteries are incubated with VEGF, there are dose-dependent alterations in endothelium-dependent behavior, mirroring those found after incubation with plasma from patients with preeclampsia.

Activation of endothelial cells by plasma from women with preeclampsia: differential effects on four endothelial cell types.

OBJECTIVE: To compare the ability of plasma from a population of women with preeclampsia and a population of plasma from women with normal pregnancies to activate four different endothelial cell types. METHODS: The secretion of nitrite and 6-keto prostaglandin F1 alpha by four endothelial cell types (isolated from the microvasculature of human decidua and skin, as well as a human umbilical vein endothelial cell line and a bovine coronary microvascular cell line) was assessed following a 24-hour incubation with plasma samples from the two groups. RESULTS: Nitrite production (an indicator of nitric oxide release) was detectable in only the decidual endothelial cells and the bovine microvascular endothelial cells (B-88), whereas 6-keto prostaglandin F1 alpha (stable metabolite of prostacyclin) was detectable in all cells. Only in the B-88 cells was there a greater production of nitrite or 6-keto prostaglandin F1 alpha in response to incubation with plasma from the preeclamptic patients when compared to plasma from the normotensive controls. CONCLUSION: The different responses of various endothelial cell types to the activating effects of plasma from preeclamptic women indicate that another important caveat to be considered when bioassaying for the circulating factor(s) of preeclampsia is the choice of endothelial cell to be studied.