Predictive value of pulse oximetry for the development of fetal acidosis.

AIMS: To determine the predictive value of fetal pulse oximetry (FPO) for the development of fetal acidosis in cases of non-reassuring fetal heart rate (FHR). METHODS: In a prospective observational study, pulse oximetry monitoring was examined in cases of non-reassuring FHR during singleton cephalic delivery at 36-42 weeks' gestation. The study examined whether fetal arterial oxygen saturation (FSpO(2)) values <30% for at least 10 min during the last 60 min before delivery increase the risk of fetal acidosis. The predictive reliability of this algorithm and the correlation to fetal acidosis [umbilical artery pH (UApH) <7.15] were analyzed. RESULTS: We included 101 patients with non-reassuring FHR during delivery. The incidence of fetal acidosis was significantly higher when FSpO(2) values <30% were recorded for at least 10 min (P=0.0). An UApH <7.15 was reliably excluded with a negative predictive value of 98.7% and detected with a sensitivity of 92.9%. CONCLUSIONS: A low pulse oximetry oxygen saturation <30% for at least 10 min correlates highly with fetal acidosis in cases of non-reassuring FHR. FPO reliably excludes moderate to advanced acidosis and can reduce the frequency of fetal blood analysis (FBA) in cases of non-reassuring cardiotocography (CTG).

Diagnosis and treatment of peripartum bleeding.

Severe peripartum hemorrhage (PPH) contributes to maternal morbidity and mortality and is one of the most frequent emergencies in obstetrics, occurring at a prevalence of 0.5-5.0%. Detection of antepartum risk factors is essential in order to implement preventive measures. Proper training of obstetric staff and publication of recommendations and guidelines can effectively reduce the frequency of PPH and its resulting morbidity and mortality. Therefore, an interdisciplinary expert committee was formed, with members from Germany, Austria, and Switzerland, to summarize recent scientific findings. An up-to-date presentation of the importance of embolization and of the diagnosis of coagulopathy in PPH is provided. Furthermore, the committee recommends changes in the management of PPH including new surgical options and the off-label use of recombinant factor VIIa.

Below median birth weight in appropriate-for-gestational-age preterm infants as a risk factor for bronchopulmonary dysplasia.

AIMS: To assess the presence of chorioamnionitis and intrauterine growth as prenatal risk factors for broncho pulmonary dysplasia (BPD) in appropriate-for-gestational-age (AGA) infants of <28 weeks' gestation. METHODS: Gender, race, birth weight, gestational age, histology of the placenta, diagnosis of BPD at 36 weeks' gestation, postnatal dexamethasone treatment, and death were recorded in 150 preterm infants born at <28 weeks' gestation, and admitted between 1996 and 2001. RESULTS: In 122 AGA infants (mean gestational age: 26.18 weeks, mean birth weight: 837 g), BPD was associated with gestational age-related birth weights below the 50(th) centile. Intrauterine growth deceleration started between 25 and 26 weeks' gestation. Chorioamnionitis was not related to BPD. CONCLUSIONS: AGA infants of 26-28 weeks' gestation with birth weights below the median showed an increased risk of developing BPD.

Using recombinant activated factor VII, B-Lynch compression, and reversible embolization of the uterine arteries for treatment of severe conservatively intractable postpartum hemorrhage: new method for management of massive hemorrhage in cases of placenta increta.

OBJECTIVE: To investigate a new method for management of massive postpartum hemorrhage in cases of abnormal placenta adhesion. DESIGN: Case report. SETTING: University hospital. PATIENT(S): An 18-year-old nullipara presented with fulminant postpartum bleeding after cesarean section due to placenta increta. The patient developed hemorrhagic and septic shock associated with disseminated intravascular coagulation. INTERVENTION(S): Treatment with uterotonic drugs like oxytocin and prostaglandins and conservative procedures like transfusion of packed red cells and fresh frozen plasma failed to control the diffuse bleeding. Further intervention consisted of B-Lynch sutures, recombinant activated factor VII, and reversible embolization of the uterine arteries. RESULT(S): The bleeding stopped after operative B-Lynch compression and recombinant activated factor VII. In the interval, the bleeding continued under therapeutically resistant disseminated intravascular coagulation, and finally bilateral reversible embolization of the uterine arteries was performed to avoid an emergency hysterectomy to preserve fertility in this young woman. CONCLUSION(S): This is a case of abnormal placenta adhesion with massive postpartum hemorrhage in which different conservative and operative treatments were combined to avoid a hysterectomy with loss of fertility and major psychological impact for the young mother.

Antibiotic therapy for preterm premature rupture of membranes - results of a multicenter study.

AIMS: To evaluate whether primary application of mezlozillin in preterm premature rupture of membranes (pPROM) prolongs pregnancy and lowers neonatal morbidity. METHODS: In this prospective, randomized, double blind, placebo-controlled multicenter study a total of 105 pregnant women with pPROM between 24 + 0 and 32 + 6 weeks of gestation were examined receiving i.v. injections of corticoids and tocolytics as well as mezlocillin (3 x 2 g/d) or placebo. Assessed factors were prolongation of pregnancy and neonatal morbidity such as neonatal infection, respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC). RESULTS: Prolongation of pregnancy by more than 7 days was achieved in 63.8% of the mezlocillin group versus 44.8% of the placebo group (P < 0.05). The babies of mothers treated with anibiotics had fewer neonatal infections, RDS, IVH and NEC. Total morbidity was significantly lowered in the verum group (P = 0.02). CONCLUSIONS: Antibiotic administration following preterm premature rupture of membranes is associated with a prolongation of pregnancy and a reduction of neonatal infectious morbidity.

Antihypertensive therapy in patients with pre-eclampsia: A prospective randomised multicentre study comparing dihydralazine with urapidil.

BACKGROUND: Drug treatment is imperative for pregnant women with pregnancy-induced hypertension (PIH) and pre-eclampsia. For more than 40 years, dihydralazine has been the drug of choice for this indication. Another particularly effective and better tolerable antihypertensive is urapidil. Yet only a few studies on limited patient collectives have been published on the clinical experience with urapidil in PIH. METHODS: Urapidil was interindividually compared to dihydralazine in a total of 42 patients, at six participating clinical centres. Patients were randomly assigned to the treatment groups. Urapidil was administered at an initial dose of 12.5-25mg, dihydralazine was administered at a uniform initial dose of 5mg. Patients were closely monitored for the initial 24h of therapy. Until delivery and in the postpartal phase, mother and baby underwent four additional follow-up checks at regular intervals. RESULTS: Either drug was effective in lowering BP. Urapidil treatment proved to be better controllable. There were clear differences as to tolerability. In the urapidil group, one patient complained of headaches. In the dihydralazine group, six patients experienced adverse occurrences. Under dihydralazine treatment, some marked HR increases occurred, interpretable as reflectory tachycardia. CONCLUSIONS: Urapidil proved to be equally effective as dihydralazine in lowering BP in patients with pre-eclampsia, but showed a better controllability and tolerability. Urapidil can hence be recommended as a promising alternative for patients with PIH.

Soluble vascular endothelial growth factor receptor-1 (sFLT-1) mediates downregulation of FLT-1 and prevents activated neutrophils from women with preeclampsia from additional migration by VEGF.

Neutrophil activation and increased migration is associated with preeclampsia and is resolved after delivery. Preeclampsia is an inflammatory disorder where altered levels of vascular endothelial growth factor (VEGF) and the circulating soluble fms-like tyrosine kinase 1 (sFlt-1) have a pathogenic role. VEGF, by binding to FLT-1, induces leukocytic chemotaxis. We studied expression and function of FLT-1 in maternal neutrophils during preeclampsia and normal pregnancies. Analysis of maternal neutrophils showed the relationship between FLT-1 expression and week of gestation. Preeclamptic women express lower FLT-1 and sFLT-1 in neutrophils. In contrast, serum levels of sFLT-1 in patients with preeclampsia are increased and, therefore, inhibit upregulation of FLT-1 in neutrophils by neutralizing VEGF. VEGF-dependent FLT-1 expression is regulated by changing FLT-1-promoter activity. Promoter activity is decreased by sFLT-1. In vitro experiments demonstrated that migration of neutrophils is regulated by VEGF via FLT-1 and excess of sFLT-1. Thus, VEGF-dependent migration of neutrophils is decreased during preeclampsia as a consequence of excess circulating sFlt1. But, they still increase migration by fMLP and, therefore, migration of neutrophils from preeclamptic women is highly activated when compared with the normotensive group. In conclusion, besides being involved in inducing an antiangiogenic state in the serum, excess of sFLT-1 seems to prevent activated neutrophils from women with preeclampsia from additional migration by VEGF. We provide evidence that neutrophils may be involved in the pathophysiology of pregnancy-related hypertensive disorders.

Shear stress-induced up-regulation of the intermediate-conductance Ca(2+)-activated K(+) channel in human endothelium.

OBJECTIVE: Wall shear stress associated with blood flow is a major stimuli for generation of endothelial vasodilating and antithrombotic factors and it also regulates endothelial gene expression. Activation of endothelial intermediate-conductance Ca(2+)-activated K(+) channels (IK(Ca)) is important for the control of endothelial function by inducing cell hyperpolarization and thus generation of the endothelium-derived hyperpolarizing factor. In the present study we tested whether the IK(Ca) encoding IKCa1 gene is regulated by laminar shear stress (LSS). METHODS: Human umbilical vein endothelial cells (HUVEC) were subjected to LSS with a magnitude of 0.5-15 dyn/cm(2) and time intervals of 2-24 h in a flow cone apparatus. Expression of the IKCa1 gene and IK(Ca)-functions were determined by using real time RT-PCR and patch-clamp techniques. RESULTS: A short 2-4 h-or long 24 h-exposure to a LSS with a low (venous) magnitude of 0.5 dyn/cm(2) had no effect on IKCa1 expression levels. An exposure for 2 and 4 h to LSS with an intermediate magnitude of 5 dyn/cm(2) was also ineffective, whereas an exposure for 24 h induced a significant threefold up-regulation of IKCa1 expression levels. An exposure to LSS with a higher (arterial) magnitude of 15 dyn/cm(2), resulted in an eightfold up-regulation of IKCa1 expression levels after a 4 h-exposure and a fourfold increase of IKCa1 expression levels at 24 h. The increased IKCa1 expression levels following exposure to high levels of LSS resulted in enhanced IK(Ca) whole-cell currents and in an increased hyperpolarization of the endothelium in response to ATP and the IK(Ca) opener 1-EBIO. Inhibition of the mitogen-activated protein kinase/extracellular-signal-regulated kinase (ERK) kinase 1/2 (MEK/ERK) pathway by PD98059 prevented the LSS-induced up-regulation of IKCa1 expression levels and IK(Ca) whole-cell currents indicating that augmentation of IKCa1 expression levels is mediated by the LSS-induced activation of the MEK/ERK pathway. CONCLUSION: Long term exposure to LSS up-regulates expression and function of endothelial IK(Ca). This increase might represent a new important mechanism in endothelial adaptation to altered hemodynamics.

Parent bisphenol A accumulation in the human maternal-fetal-placental unit.

Bisphenol A (BPA), an endocrine disruptor, is employed in the manufacture of a wide range of consumer products. The suggestion that BPA, at amounts to which we are exposed, alters the reproductive organs of developing rodents has caused concern. At present, no information exists concerning the exposure of human pregnant women and their fetuses to BPA. We therefore investigated blood samples from mothers (n = 37) between weeks 32 and 41 of gestation. Afer the births, we also analyzed placental tissue and umbilical cord blood from the same subjects. We developed a novel chemical derivatization-gas chromatography/mass spectrometry method to analyze parent BPA at concentrations < 1 micro g/mL in plasma and tissues. Concentrations of BPA ranged from 0.3 to 18.9 ng/mL (median = 3.1 ng/mL) in maternal plasma, from 0.2 to 9.2 ng/mL (median = 2.3 ng/mL) in fetal plasma, and from 1.0 to 104.9 ng/g (median = 12.7 ng/g) in placental tissue. BPA blood concentrations were higher in male than in female fetuses. Here we demonstrate parent BPA in pregnant women and their fetuses. Exposure levels of parent BPA were found within a range typical of those used in recent animal studies and were shown to be toxic to reproductive organs of male and female offspring. We suggest that the range of BPA concentrations we measured may be related to sex differences in metabolization of parent BPA or variable maternal use of consumer products leaching BPA.

Up-regulation of endothelial stretch-activated cation channels by fluid shear stress.

OBJECTIVE: Stretch-activated cation channels (SAC) have been suggested to act as endothelial mechanosensors for hemodynamic forces. Ca(2+) influx through SAC could induce an intracellular Ca(2+) signal stimulating Ca(2+)-dependent synthesis of vasodilators like NO, prostacyclin, or EDHF. In the present study we tested whether laminar shear stress (LSS) regulates SAC function. METHODS: Electrophysiological properties of SAC were investigated in human umbilical vein endothelial cells (HUVEC) subjected to defined levels of LSS in a flow-cone apparatus. RESULTS: In HUVEC, we identified a Ca(2+) permeable SAC that was activated by membrane stretch. Single-channel current densities of SAC in cell-attached patches were significantly increased in HUVEC exposed to an LSS of 5 dyn/cm(2) for 4 h (1.15+/-0.17 SAC/patch) compared to HUVEC kept in stationary culture (0.46+/-0.07 SAC/patch). Exposure of HUVEC to a higher LSS of 15 dyn/cm(2) for 4 h induced similar up-regulation of SAC (1.27+/-0.21 SAC/patch). After 24 h exposure to LSS of 15 dyn/cm(2), single-channel current densities of SAC remained up-regulated (1.07+/-0.18 SAC/patch) compared to controls. In addition, stretch-sensitivity of SAC (channel activity NP(o) at -30 mmHg) significantly increased after 2 h of exposure to LSS of 5 and 15 dyn/cm(2) and remained up-regulated after 24 h. Inhibition of protein kinases and tyrosine kinases by H7 and genistein, respectively, prevented LSS-induced alteration of SAC function. CONCLUSION: Single-channel current density and mechanosensitivity of SAC in HUVEC is up-regulated by LSS. Up-regulation of SAC function leads to enhanced mechanosensitive Ca(2+) influx, and represents a novel adaptive mechanism of the endothelium in the presence of altered hemodynamic forces.