[Management of postpartum hemorrhage (PPH): algorithm of the interdisciplinary D-A-CH consensus group PPH (Germany - Austria - Switzerland)]. / Management der postpartalen Blutung (PPH): Algorithmus der Interdisziplinären D-A-CH-Konsensusgruppe PPH (Deutschland - Österreich - Schweiz).

Postpartum hemorrhage (PPH) is one of the main causes of maternal deaths even in industrialized countries. It represents an emergency situation which necessitates a rapid decision and in particular an exact diagnosis and root cause analysis in order to initiate the correct therapeutic measures in an interdisciplinary cooperation. In addition to established guidelines, the benefits of standardized therapy algorithms have been demonstrated. A therapy algorithm for the obstetric emergency of postpartum hemorrhage in the German language is not yet available. The establishment of an international (Germany, Austria and Switzerland D-A-CH) "treatment algorithm for postpartum hemorrhage" was an interdisciplinary project based on the guidelines of the corresponding specialist societies (anesthesia and intensive care medicine and obstetrics) in the three countries as well as comparable international algorithms for therapy of PPH.The obstetrics and anesthesiology personnel must possess sufficient expertise for emergency situations despite lower case numbers. The rarity of occurrence for individual patients and the life-threatening situation necessitate a structured approach according to predetermined treatment algorithms. This can then be carried out according to the established algorithm. Furthermore, this algorithm presents the opportunity to train for emergency situations in an interdisciplinary team.

[Impact of iatrogenic preterm birth on newborn morbidity]. / Einfluss der iatrogenen Frühgeburt auf die frühkindliche Morbidität.

The incidence of premature births is not decreasing in developed countries, but rather shows a tendency to increase. This rise is primarily due to an increase in the number iatrogenic late preterm births at a gestational age between 34 + 0 and 36 + 6 weeks. Late preterm births account for up to 80% of all preterm births and these newborns have higher morbidity and mortality rates and a higher rate in neurodevelopmental long-term impairment in comparison to term infants. In order to reduce iatrogenic preterm birth, it is necessary to apply standardised treatment algorithms especially in cases of mild preeclampsia and intrauterine growth restriction.

Decreased umbilical artery compliance and igf-I plasma levels in infants with intrauterine growth restriction - implications for fetal programming of hypertension.

Epidemiological studies link intrauterine growth restriction (IUGR) to arterial hypertension in adulthood. We compared umbilical arteries from IUGR (n=12, <5th weight percentile) vs. appropriate for gestational age (AGA) infants (n=12) using structural and functional analyses. The vessel wall area of umbilical arteries in the IUGR group was significantly smaller than in the AGA group (2.8 vs. 3.8mm(2), P<0.05). Myographic measurements showed that maximal tension [mN/mm] as well as maximal force [mN] were both significantly increased in IUGR arteries compared with AGA arteries (P<0.05). Serum levels of IGF-I, a regulator of elastin synthesis, were significantly lower in IUGR cord blood (P<0.01) than in AGA cord blood. These IGF-I serum levels correlated significantly with maximum tension in umbilical arteries (P<0.01). Low intrauterine IGF-I serum levels may account for thinner and stiffer umbilical arteries in IUGR infants in comparison to AGA infants thereby providing a potential link to arterial hypertension in adulthood.

Changes in olfactory function with several pregnancies?

OBJECTIVE: To investigate whether olfactory performance decreases as a function of the number of pregnancies, previous research having indicated that olfactory function decreases in the course of pregnancy. METHODS: In a prospective study three groups of women were investigated (total n = 93), women who have given birth to no children (group 0), to one child (group 1), and to two or three children (group 2). Olfactory function was assessed using the "Sniffin' Sticks" kit. RESULTS: There was no significant difference in olfactory function between the three groups. CONCLUSION: While pregnancy is typically accompanied by changes in olfactory performance, these alterations obviously do not translate into a long-lasting change in olfactory function dependent on the number of pregnancies.

[Calcium-supplementation in pregnancy--is it a must?]. / Kalziumsupplementation in der Schwangerschaft--ein Muss (?).

The pregnant woman's body provides daily doses between 50 and 330 mg to support the developing fetal skeleton. This high fetal demand for calcium in pregnancy is facilitated by profound physiological interactions between mother and fetus. The D-A-CH organization (which represents the German, Austrian and Swiss Nutrition Offices) and the Institute of Medicine (IOM) of the US recommend a daily consumption of 1000 mg calcium for pregnant and lactating women at an age over 19 years. The average consumption of calcium in western countries is about 800 mg in young women. Therefore calcium consumption in pregnancy should be encouraged, especially during the second and third trimester of pregnancy and during lactation. Proper calcium consumption can be attained by diet with healthy nourishment including 3-4 snacks of milk or milk-derived products such as yogurt and cheese and calcium-rich mineral waters. In these women calcium-supplementation in pregnancy is not necessary. In women with chronic autoimmunologic disorders, low-molecular-weight-heparin therapy during pregnancy, lactose intolerance or in women who prefer to skip milk and milk products due to personal preference the supplementation of 500 to 1000 mg calcium in addition to dietary measures is recommended. Calcium supplementation in pregnancy has been associated with a reduced risk of pregnancy-induced hypertension, but this effect is only seen in persons with a low basal calcium intake. There are reports in literature that calcium supplementation in pregnancy protects against low-birthweight in newborns, which is defined as a birthweight of < 2500 g or that calcium supplementation lowers offspring blood pressure thus helping to prevent hypertension in the next generation. These reports are either preliminary or are not applicable to the Swiss population or need confirmation. Therefore calcium supplementation is only recommended in order to achieve a daily uptake of at least 1000 mg/day in pregnant women.

Recent insights into the roles of nitric oxide and renin-angiotensin in the pathophysiology of preeclamptic pregnancy.

Normal pregnancy involves marked maternal hemodynamic adaptations; these are suppressed in preeclampsia, leading to serious complications for mother and baby. The cause of preeclampsia is unknown, but may involve primary pathology at the maternal/fetal interface. However, the systemic manifestations of the disease are associated with widespread maternal vascular endothelial damage and dysfunction. There has been considerable recent interest in the possible roles for nitric oxide (NO) deficiency and for alterations in the renin angiotensin system (RAS) in the pathophysiology of preeclampsia. The following is an overview of the hemodynamic responses to normal pregnancy, an evaluation of the possible roles of NO and the RAS in these adaptations, and a review of the important aspects of these systems in preeclampsia.

Adrenomedullin gene expression in human placental tIssue and leukocytes: a potential marker of severe tIssue hypoxia in neonates with birth asphyxia.

OBJECTIVE: The aim of the present study was to investigate the role of adrenomedullin (ADM) as a hypoxia-inducible marker of clinically relevant tIssue hypoxia in acute birth asphyxia of term newborn infants. METHODS: For this purpose, ADM mRNA was determined in human placental tIssue of 20 term pregnancies complicated by birth asphyxia (pH and base deficit values, clinical score). In addition, ADM mRNA was measured in leukocytes of the asphyxiated newborn infants during the first 12 h of life (n=12). Controls were available from ten healthy term pregnancies. In vitro, hypoxia-inducible expression of ADM mRNA was evaluated in human choriocarcinoma cells (BeWo) and human leukocytes exposed to hypoxia (1% O(2)) for 1-24 h. mRNA levels were measured by TaqMan real-time PCR. RESULTS: In vitro, ADM mRNA related to porphobilinogen deaminase (PBGD) mRNA levels significantly increased in response to hypoxia within a period of 4 h in leukocytes and 12 h in BeWo cells. In human placental tIssue, significantly higher levels of ADM/PBGD mRNA were present in asphyxiated newborn infants with severe hypoxic-ischemic encephalopathy (HIE) (n=5) compared with patients with mild or no HIE (n=15). Increased levels of ADM/PBGD mRNA levels were found during the first hours of life in leukocytes of neonates with severe HIE compared with controls. CONCLUSIONS: Our results indicate an upregulation of ADM gene expression in human placenta and leukocytes in clinically relevant hypoxic-ischemic birth complications and suggest ADM gene expression as a promising marker for severe complications due to perinatal asphyxia such as HIE.

Skin flux during reactive hyperemia and local hyperthermia in patients with preeclampsia.

OBJECTIVE: To test the contribution of the endothelium to the maximum vasodilatation in patients with preeclampsia and healthy pregnant controls. METHODS: Laser-Doppler flowmetry, which is a noninvasive method for the continuous measurement of skin blood flow, was used to test the response of skin microcirculation to the above-mentioned stimuli in 14 patients with preeclampsia and 20 normotensive pregnant controls. RESULTS: In normotensive pregnant controls, the reactive hyperemic response after a 3-minute ischemia in the forearm reaches values of 77 +/- 16% of the maximum vasodilatation, which was induced by local hyperthermia of 42C. In patients with preeclampsia, this response was significantly (P <.05) reduced (43 +/- 9%). CONCLUSION: Vascular reactivity is altered in skin vessels of patients with preeclampsia in vivo. This alteration seems to be attributable mainly to the endothelium.

Prenatal findings in patients with prolonged QT interval in the neonatal period.

OBJECTIVE: To describe prenatal abnormalities of cardiac rhythm in patients with prolonged QT interval in the neonatal period. DESIGN: A retrospective analysis of the results of fetal echocardiography and the outcome in patients with prolonged QT interval in the neonatal period who had been referred for prenatal evaluation. SETTING: Two university hospitals. PATIENTS: Nine patients with prolonged QT interval in the neonatal period who had been referred for prenatal evaluation. Fetal echocardiograms were obtained from 24 to 40 weeks of gestation. Indications were fetal bradycardia (five patients), a family history of long QT syndrome (two patients), and complex arrhythmias (two patients). RESULTS: Seven fetuses had persistent sinus bradycardia without ventricular arrhythmias (heart rates 70-120 beats/ min). Five patients were treated with propranolol, after the diagnosis had been established by postnatal electrocardiogram (ECG). One of these patients died suddenly at the age of 3 weeks, after the treatment had been stopped because of profound bradycardia. One of the remaining two patients who did not receive propranolol had a syncope at the age of 6 weeks. Two fetuses presented with frequent runs of ventricular tachycardia and intermittent bradycardia caused by intermittent, functional second degree atrioventricular block. Both patients died on the first day of life despite treatment with propranolol and transvenous temporary pacing. CONCLUSIONS: Sinus bradycardia in an otherwise normal fetus may be a symptom of long QT syndrome. Postnatal ECGs and a family examination are strongly recommended in these children. In fetuses with frequent runs of ventricular tachycardia and intermittent second degree atrioventricular block long QT syndrome should be suspected prenatally. These high risk patients should be delivered in centres with a paediatric cardiology unit.

Influence of reduced intracellular glutathione availability on the secretion of vasoactive substances by human umbilical vein endothelial cells.

OBJECTIVE: Oxidative stress might be the reason for endothelial dysfunction in preeclampsia. The glutathione-peroxidase system is one of the primary antioxidants in the endothelium. We tested the effect of oxidative stress by reduction of glutathione availability on the secretion of vasoactive substances in endothelial cells. METHODS: Endothelial cells in culture were incubated with different concentrations of buthionine-[S,R]-sulfoximine (BSO) or 1-chloro-2,4-dinitrobenzene (CDNB), both leading to a reduced intracellular availability of glutathione. The secretion of the vasoactive substances nitric oxide (NO), endothelin-I (ET-1), and prostacyclin (PGI2) was measured with respect to vitality and proliferation rate of the endothelial cells in culture. MAIN OUTCOME MEASURE: Effect of oxidative stress on the secretion of vasoactive substances from endothelial cells. RESULTS: The oxidants CDNB and BSO have (in concentrations before evidence of cytotoxicity) a stimulating effect on the production of PGI2, they inhibit NO availability, and they do not significantly interfere with ET-1 production. Conclusion Oxidative stress in vitro induces an imbalance in the secretion of NO, ET-1, and PGI2 in endothelial cells.

Nitric oxide synthase activity and Doppler parameters in the fetoplacental and uteroplacental circulation in preeclampsia.

OBJECTIVE: We investigated the hypothesis that changes in blood flow in the uteroplacental and fetoplacental circulation in preeclampsia are associated with an abnormality of placental or uterine placental bed nitric oxide (NO) synthesis. METHODS: We measured pulsatility indices on Doppler waveform analysis from uterine and umbilical arteries in 20 patients with preeclampsia and 14 healthy pregnant controls before elective cesarean section. During cesarean section, biopsies from the uterine placental bed and the placenta were taken and the nitric oxide synthase (NOS) activity was measured by the [3H] L-arginine-[3H] L-citrulline conversion assay in these samples. RESULTS: The NOS activity was significantly lower in the uterine placental bed in comparison to the placental tissue (p < 0.01). Placental NOS activity was similar between patients with preeclampsia and healthy controls and in the groups with either a pathological or a normal Doppler flow in the umbilical artery. In the uterine placental bed however, NOS activity from patients with preeclampsia was significantly lower (p < 0.01), whereas the blood flow resistance in the uterine arteries was elevated (p < 0.01) in comparison to healthy controls. CONCLUSIONS: Our data show that pathological Doppler waveforms in the uterine arteries of patients with preeclampsia are paralleled by diminished NOS activity in the uterine placental bed. Therefore, the compromised NO production in the uterine placental bed may play an important role in the impaired uteroplacental blood flow and potentially in some pathological features of preeclampsia such as intervillous thrombosis formation and fetal growth retardation.

Production of vasoactive substances by human umbilical vein endothelial cells after incubation with serum from preeclamptic patients.

OBJECTIVE: To determine the in vitro effect of serum from preeclamptic patients on the proliferation, viability and secretion of vasoactive substances by human umbilical vein endothelial cells (HUVEC). STUDY DESIGN: HUVEC were incubated for 24h with sera from 16 preeclamptic, 19 healthy pregnant and 8 healthy nonpregnant women. Proliferation rates were determined by cell counting and vitality by trypan blue staining. The vasoactive substances, 6-keto-prostaglandin F(1alpha), nitrite and nitrate, and endothelin-1 (ET-1) were measured in endothelial cell supernatants. RESULTS: The preeclamptic serum had no effect on cell proliferation or vitality compared with control sera. It induced more HUVEC production of ET-1, but not of prostacyclin (PGI2) or nitric oxide compared with control serum. CONCLUSION: Preeclamptic serum appears to contain a factor(s) that specifically stimulates ET-1 secretion from HUVEC without altering cell growth or vitality.

Surgery of a splenic artery aneurysm during pregnancy.

We report a case of ligation of the splenic artery with splenectomy during pregnancy due to a splenic artery aneurysm. The risk of aneurysmal rupture is increased in multipara and during pregnancy. As a result of high maternal and fetal morbidity and mortality elective surgery should be performed.

Surgical treatment of HELLP syndrome-associated liver rupture -- an update.

In some 2% of the cases of the HELLP syndrome, severe spontaneous bleeding into the liver accompanied by haemorrhagic liver cell necrosis and rupture of the organ occurs and represents one of the main cause of death. On the basis of our own experience with four cases, a review of the literature is presented with particular focus on a therapeutic concept based on appropriate surgery. Within a MEDLINE search covering the period 1990-1999, the case reports of this kind of liver complication in the literature were analysed in terms of clinical course and outcome.In addition to our own four patients, a total of 49 cases with rupture of the liver were found in the literature. Despite surgical interventions, HELLP syndrome-associated liver rupture carried a mortality of 39%. Most patients died of haemorrhagic shock and organ failure. In order to improve survival, patients with ruptured liver or hepatic failure should be transferred to a centre with the necessary experience in liver surgery including liver transplantation. An interdisciplinary approach is required, including the use of temporary packing of the liver to control the bleeding, and during the further course of the condition, possibly even liver transplantation, as in one of our own cases.

Laser Doppler technique for the measurement of digital and segmental systolic blood pressure.

A technique is described for measuring digital and segmental systolic blood pressure by laser Doppler fluxmetry. A transparent plastic capsule contains the small sphygmomanometer cuff connected to a Statham manometer. It has a hole for positioning the probe at the very tips of fingers or toes. An advantage of this method over the conventional strain-gauge technique is that it is better suited for determinations at short digits where it is difficult to fix a strain-gauge. Moreover, it allows consecutive pressure and flux measurements at almost identical distal sites without moving the probe. The correlation between the values obtained by the conventional and laser Doppler procedures are excellent. Systolic pressures were determined on 14 extremities of 7 healthy controls and on 20 extremities of 14 patients with intermittent claudication due to peripheral arterial occlusive disease. Measuring sites were the upper arm, forearm, index finger, ankle and big toe. The values agree well with those obtained earlier by the strain-gauge technique.

Intrauterine subdural hemorrhage in a preterm neonate possibly associated with maternal low-molecular weight heparin treatment.

We report intrauterine subdural hemorrhage in a preterm infant delivered by cesarean section at 32 weeks following vaginal bleeding of a mother treated with low-molecular weight heparin (LMWH) for deep vein thrombosis. The subdural hematomas were partially calcified, proving antenatal occurrence. Maternal trauma during pregnancy, intrauterine infection, cerebral vascular malformation and congenital coagulopathy as known etiologies of subdural hemorrhage could be ruled out. Intrauterine subdural hemorrhage may be an exceptional complication of maternal LMWH treatment.

[The impact of epidural analgesia on birth experience]. / Auswirkungen der Periduralanästhesie (PDA) auf das Geburtserlebnis.

BACKGROUND: The satisfaction of our patients with the intrapartum analgesia and differences between labour with and without epidural analgesia (EDA) were analysed retrospectively. PATIENTS AND METHODS: In March 2004 questionnaires were sent to all women who gave birth between 1 January 2003 and 30 June 2003 at the University Hospital of Zurich. RESULTS: 45.5% of the questionnaires were returned. The EDA-rate reached 47.3%. Women with EDA had a significant longer delivery and the vacuum was more often used (p < 0.001 each). There was no difference between births with or without EDA concerning Apgar- and pH-scores from the umbilical artery. Several factors had an impact on satisfaction: higher age (> 30 years) (p = 0.012), the feeling that this labour was less painful than the previous (p = 0.010), the ability to control labour pain (p = 0.002), to influence drug therapy of pain (p < 0.001). CONCLUSION: Our results show, that the individual care and involvement of women in the birth process and pain therapy had a greater influence on satisfaction with birth than the type of analgesia.