[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.

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.

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.

[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.

Hypoxia activates the human placental vascular endothelial growth factor system in vitro and in vivo: up-regulation of vascular endothelial growth factor in clinically relevant hypoxic ischemia in birth asphyxia.

OBJECTIVE: We investigated the influence of acute hypoxia on the placental vascular endothelial growth factor system in vitro and in vivo in acute birth asphyxia compared with pregnancies that were complicated by preeclampsia and with healthy control subjects. STUDY DESIGN: Messenger RNA levels for vascular endothelial growth factor, flt-1, and KDR were measured by TaqMan real-time polymerase chain reaction in human placental choriocarcinoma cells (BeWo) that were exposed to hypoxia (1% oxygen, 5% carbon dioxide, 94% nitrogen) and in placental tissue of neonates with birth asphyxia (n = 20), newborn infants of mothers with preeclampsia (n = 20), and gestational age-matched control subjects. Immunhistologically, placental vascular endothelial growth factor protein expression was compared among the groups. RESULTS: In BeWo cells, vascular endothelial growth factor, flt-1 and KDR messenger RNA increased in a time-dependent manner in response to hypoxia. In vivo, vascular endothelial growth factor/beta-actin and KDR/beta-actin messenger RNA were significantly higher in placental tissue of newborn infants with severe hypoxic-ischemic encephalopathy than with newborn infants with mild or no hypoxic-ischemic encephalopathy and control subjects. In chronic placental hypoxia (preeclampsia), vascular endothelial growth factor and both receptors were found to be up-regulated. Increased placental vascular endothelial growth factor expression was confirmed by immunohistologic examination. CONCLUSION: The vascular endothelial growth factor system is up-regulated in response to placental hypoxia and is assumed to be a potential early indicator of severe birth asphyxia.

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.

Effect of endothelin-1 on intracellular glutathione and lipid peroxide availability and on the secretion of vasoactive substances by human umbilical vein endothelial cells.

BACKGROUND: The major pathophysiologic changes observed in preeclampsia suggest that endothelial cell dysfunction plays an important role in this disorder. The pathway mediating endothelial cell layer dysfunction is unknown. The concentration of endothelin-1 (ET-1), a potent mammalian vasoconstrictor peptide produced by the vascular endothelium, has been observed to be significantly increased in preeclampsia. In this study, we determined the in vitro effect of endothelin-1 on glutathione and lipid peroxide levels and on the secretion of vasoactive substances by human umbilical vein endothelial cells (HUVECs). METHODS: Human umbilical vein endothelial cells were incubated for 24 h in the presence of different concentrations of ET-1 (0-1000 pmol L(-1)), which were shown in an earlier experiment to have no effects on vitality and proliferation rate of HUVECs. The levels of glutathione (GSH) and lipid peroxides (LPO) were measured in endothelial cell lysates. For the measurement of vasoactive substances, levels of nitric oxide (NO), prostacyclin (PGI2) and thromboxane A2 (TXA2) were measured in endothelial cell supernatants. RESULTS: At lower concentrations (5-50 pmol L(-1)), ET-1 increases the intracellular content of LPO, stimulates the secretion of TXA2, but inhibits the secretion of PGI2 in endothelial cells compared with control cells. At higher concentrations (100-1000 pmol L(-1)), ET-1 increases the intracellular content of GSH, but results in a decrease of LPO, and increase of PGI2, back to control levels. ET-1 has no effect on NO secretion. CONCLUSION: These findings demonstrate that at concentrations corresponding to values in plasma from preeclamptic women, ET-1 induces oxidative stress and results in altered secretion of vasoactive substances in human endothelial cells. We conclude that ET-1 may participate in the pathway leading to endothelial cell dysfunction seen in preeclampsia.

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.

Fetal sinus bradycardia and the long QT syndrome.

OBJECTIVE: Recent evidence in literature shows that the long QT syndrome accounts for a fraction of the sudden infant death syndrome. Newborn infants with prolongation of the Q-T interval often show sinus bradycardia, which led us to test whether children who were diagnosed with long QT syndrome also show sinus bradycardia in the cardiotocogram before birth. STUDY DESIGN: We identified 18 children who were born from singleton pregnancies at or near term in whom long QT syndrome (corrected QT interval, >0.440 second) was diagnosed after birth or in childhood. Cardiograms during pregnancy and delivery were available from 17 of the 18 children. RESULTS: The cardiotocogram showed persistent fetal sinus bradycardia (baseline heart rate permanently below 120 beats/min) in 12 of 17 fetuses (71%) with long QT syndrome. Two fetuses had additional intermittent tachyarrhythmias. CONCLUSION: Sinus bradycardia in the cardiotocogram during delivery or in pregnancy may indicate long QT syndrome in the fetus. Postnatal electrocardiography should be performed in these children to rule out or confirm a prolongation of the Q-T interval.

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.

Deletion 15q24-26 in prenatally detected diaphragmatic hernia: increasing evidence of a candidate region for diaphragmatic development.

Survival of children with congenital diaphragmatic hernia (CDH) is mainly dependent on the extent of lung hypoplasia and the presence of additional congenital anomalies or chromosomal aberrations. A chromosomal deletion 15q25-q26.2 in a fetus with prenatally diagnosed CDH and growth retardation is reported. Despite optimal pre- and neonatal management the baby died shortly after birth. There is increasing evidence that the long arm of chromosome 15, and especially the region 15q24 to 15q26, plays a crucial role in the development of the diaphragm. The finding of a deletion within 15q24-26 in a fetus with CDH has to be considered a predictor of poor prognosis. It is of utmost interest for proper parental counselling to search in fetuses with CDH for subtle chromosomal lesions paying special attention to chromosome 15q.

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.

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.