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Abstract Background Perinatal asphyxia is, even in developed countries, one the major causes of neonatal morbidity and mortality. Therefore, if foetal distress during labour is suspected, one should try to restore foetal oxygen levels or aim for immediate delivery. However, studies on the effect of intrauterine resuscitation during labour are scarce. We designed a randomised controlled trial to investigate the effect of maternal hyperoxygenation on the foetal condition. In this study, maternal hyperoxygenation is induced for the treatment of foetal distress during the second stage of term labour. Methods/design This study is a single-centre randomised controlled trial being performed in a tertiary hospital in The Netherlands. From among cases of a suboptimal or abnormal foetal heart rate pattern during the second stage of term labour, a total of 116 patients will be randomised to the control group, where normal care is provided, or to the intervention group, where before normal care 100% oxygen is supplied to the mother by a non-rebreathing mask until delivery. The primary outcome is change in foetal heart rate pattern. Secondary outcomes are Apgar score, mode of delivery, admission to the neonatal intensive care unit and maternal side effects. In addition, blood gas values and malondialdehyde are determined in umbilical cord blood. Discussion This study will be the first randomised controlled trial to investigate the effect of maternal hyperoxygenation for foetal distress during labour. This intervention should be recommended only as a treatment for intrapartum foetal distress, when improvement of the foetal condition is likely and outweighs maternal and neonatal side effects. Trial registration EudraCT, 2015-001654-15; registered on 3 April 2015. Dutch Trial Register, NTR5461; registered on 20 October 2015.

Following publication of the original article [1], the authors noticed that the sample size for the study group was incorrectly reported in the Methods section.

Donor cells can be preserved in University of Wisconsin (UW), histidine-tryptophan-ketoglutarate (HTK), or Celsior solution. However, differences in efficacy and mode of action in preventing hypothermia-induced cell injury have not been unequivocally clarified. Therefore, we investigated and compared necrotic and apoptotic cell death of freshly isolated primary porcine hepatocytes after hypothermic preservation in UW, HTK, and Celsior solutions and subsequent normothermic culturing. Hepatocytes were isolated from porcine livers, divided in fractions, and hypothermically (4°C) stored in phosphate-buffered saline (PBS), UW, HTK, or Celsior solution. Cell necrosis and apoptosis were assessed after 24- and 48-h hypothermic storage and after 24-h normothermic culturing following the hypothermic preservation periods. Necrosis was assessed by trypan blue exclusion, lactate dehydrogenase (LDH) release, and mitochondrial 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction. Apoptosis was assessed by the induction of histone-associated DNA fragments and cellular caspase-3 activity. Trypan blue exclusion, LDH release, and MTT reduction of hypothermically preserved hepatocytes showed a decrease in cell viability of more than 50% during the first 24 h of hypothermic preservation. Cell viability was further decreased after 48-h preservation. DNA fragmentation was slightly enhanced in hepatocytes after preservation in all solutions, but caspase-3 activity was not significantly increased in these cells. Normothermic culturing of hypothermically preserved cells further decreased cell viability as assessed by LDH release and MTT reduction. Normothermic culturing of hypothermically preserved hepatocytes induced DNA fragmentation, but caspase-3 activity was not enhanced in these cells. Trypan blue exclusion, LDH leakage, and MTT reduction demonstrated the highest cell viability after storage in Celsior, and DNA fragmentation was the lowest in cells that had been stored in PBS and UW solutions. None of the preservation solutions tested in this study was capable of adequately preventing cell death of isolated porcine hepatocytes after 24-h hypothermic preservation and subsequent 24-h normothermic culturing. Culturing of isolated and hypothermically preserved hepatocytes induces DNA fragmentation, but does not lead to caspase-3 activation. With respect to necrosis and DNA fragmentation of hypothermically preserved cells, UW and Celsior were superior to PBS and HTK solutions in this model of isolated porcine hepatocyte preservation.

Aim: This study aims to determine, based on existing data, whether the mechanism resulting in liver dysfunction in HELLP syndrome resembles that in Sinusoidal Obstruction Syndrome (SOS).Background: HELLP syndrome is a serious pregnancy disorder with high maternal and perinatal morbidity and mortality rates. Because of poor insight in its pathophysiology, particularly that of the liver involvement, clinical management is limited to symptomatic treatment, often followed by termination of pregnancy. SOS is a rare, potentially life-threatening complication of radio and/ or chemotherapy in the preparation of hematopoietic cell transplantation. The etiology of liver dysfunction in SOS is - unlike that in HELLP syndrome - better-understood and seems to be initiated by direct toxic damage and demise of endothelial cells, causing hepatic sinusoidal obstruction and ischemia.Methods: We searched Pubmed, Embase and Cochrane for reports on the etiology of HELLP and SOS. This yielded 73 articles, with 14 additional reports from the references listed in these articles.Results: The dysfunctional placenta in women developing HELLP initiates a cascade of events that eventually results in liver dysfunction. The placenta releases, besides anti-angiogenetic factors, also necrotic debris and cell-free DNA, a mixture that not only induces systemic endothelial dysfunction as in preeclampsia, but also a systemic inflammatory response. The latter aggravates the endothelio-toxic effects in the systemic cardiovascular bed, amplifying the already increased pro-thrombotic conditions. Particularly in microcirculations with extremely low shear forces, such as in the hepatic sinusoids, this will facilitate microthrombi formation and fibrin deposition eventually resulting in obstruction of the sinusoids similar as in SOS. The latter causes ischemic damage and progressive demise of hepatocytes.Conclusion: The available information supports the concept that the liver damage in HELLP and SOS results from sinusoidal ischemia, presumably resulting from partially overlapping pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Aim: With this review we try to unravel if placenta-derived factors are able to initiate liver sinusoidal endothelial cells (LSEC) decay in HELLP syndrome and eventually cause the development of sinusoidal obstruction syndrome (SOS).Background: Haemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome is a severe complication of pregnancy. It is characterized by elevated liver enzymes, low platelet count and haemolytic anaemia. The risk of developing HELLP syndrome within a pregnancy is 0.1-0.8%. The mortality rate among women with HELLP syndrome is 0-24% and the perinatal death goes up to 37%. The aetiology of HELLP syndrome is not fully understood but the pathogenesis of the liver pathology in the HELLP syndrome resembles that of a SOS with endothelial damage of the LSECs which ultimately leads to liver failure.Objectives: We hypothesize that placenta derived factors cause LSEC damage and thereby liver dysfunction.Methods: We searched in the PubMed database for relevant articles about placenta derived factors involved in endothelial activation especially in the liver. We yielded eventually 55 relevant articles.Results: Based on this literature search we associate that in HELLP syndrome there is an increase of soluble fms-like tyrosine kinase (sFlt1), vascular endothelial growth factor (VEGFR), soluble endoglin (sEng), galectin-1 (Gal-1), endothelin-1 (ET-1), Angiopoietin 2 (Angs-2), Asymmetric dimethylarginine (ADMA), activin B, inhibin A, Fas ligand (FasL) and heat shock protein 70 (Hsp70).Conclusion: We assume that these eleven increased placenta derived factors are responsible for LSEC damage which eventually leads to liver failure. This concept shows a possible design of the complicated pathophysiology in HELLP syndrome. However further research is required. [ABSTRACT FROM AUTHOR]

Objective: To describe the maternal and neonatal outcomes and prolongation of pregnancies with severe early onset pre-eclampsia before 26 weeks of gestation.Design: Nationwide case series.Setting: All Dutch tertiary perinatal care centres.Population: All women diagnosed with severe pre-eclampsia who delivered between 22 and 26 weeks of gestation in a tertiary perinatal care centre in the Netherlands, between 2008 and 2014.Methods: Women were identified through computerised hospital databases. Data were collected from medical records.Main Outcome Measures: Maternal complications [HELLP (haemolysis, elevated liver enzyme levels, and low platelet levels) syndrome, eclampsia, pulmonary oedema, cerebrovascular incidents, hepatic capsular rupture, placenta abruption, renal failure, and maternal death], neonatal survival and complications (intraventricular haemorrhage, retinopathy of prematurity, necrotising enterocolitis, bronchopulmonary dysplasia, and sepsis), and outcome of subsequent pregnancies (recurrent pre-eclampsia, premature delivery, and neonatal survival).Results: We studied 133 women, delivering 140 children. Maternal complications occurred frequently (54%). Deterioration of HELLP syndrome during expectant care occurred in 48%, after 4 days. Median prolongation was 5 days (range: 0-25 days). Neonatal survival was poor (19%), and was worse (6.6%) if the mother was admitted before 24 weeks of gestation. Complications occurred frequently among survivors (84%). After active support, neonatal survival was comparable with the survival of spontaneous premature neonates (54%). Pre-eclampsia recurred in 31%, at a mean gestational age of 32 weeks and 6 days.Conclusions: Considering the limits of prolongation, women need to be counselled carefully, weighing the high risk for maternal complications versus limited neonatal survival and/or extreme prematurity and its sequelae. The positive prospects regarding maternal and neonatal outcome in future pregnancies can supplement counselling.Tweetable Abstract: Severe early onset pre-eclampsia comes with high maternal complication rates and poor neonatal survival. [ABSTRACT FROM AUTHOR]

During pregnancy the placental 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) enzyme inactivates prednisolone by interconversion into prednisone, protecting the fetus from high levels of prednisolone. Recent reports suggest decreased placental 11β-HSD2 activity in pregnancies complicated by preeclampsia. The purpose of our investigation was to study the transplacental passage of prednisolone in patients suffering from early preterm HELLP syndrome, a severe complication of preeclampsia. We examined the maternal and umbilical cord plasma concentration of prednisolone in nine women receiving 50mg of prednisolone twice a day. Samples were obtained during caesarean section at a gestational age between 27 and 31 weeks. Mean fetal concentration was 10-fold lower as compared to maternal prednisolone concentration (mean±SD 52.8nmol/L±27.0 vs. 477.5nmol/L±300, p <0.01). A significant correlation was found between the last dose of prednisolone to delivery interval and the fetal prednisone concentration (Spearman''s correlation coefficient r =−0.946, p <0.000). Our data demonstrate unimpaired placental 11β-HSD2 activity in patients suffering from HELLP syndrome at early gestational age as shown by both a 10-fold lower fetal prednisolone concentration as compared to the mother and a strong correlation between the last dose of prednisolone to delivery interval and the fetal prednisone concentration. Prednisolone may therefore have less effect on the fetus than betamethasone or dexamethasone. [Copyright &y& Elsevier]

Introduction Severe early onset preeclampsia (PE) is a rare pregnancy disorder with a high maternal and neonatal mortality and morbidity. At an extremely premature gestational age, severe preeclampsia is rare. It causes a distinctive dilemma, as foetal and maternal interests conflict. Prolongation of pregnancy (expectant management) may improve foetal prognosis on one hand, but increases maternal risks of severe morbidity and mortality on the other hand. Objectives To compare maternal and neonatal outcomes of immediate delivery or expectant management in women with severe, early onset preeclampsia before 26 weeks’ gestation. Methods We conducted a nationwide retrospective cohort study. We included women diagnosed with severe preeclampsia, who delivered between 22 and 26 weeks’ gestation in all tertiary perinatal care centres in the Netherlands between 2008 and 2014. Patients were identified through computerized hospital databases. We collected data using the medical records. Maternal complications, neonatal mortality and neonatal complications were the primary outcomes. Results We studied 133 women, of whom 99 (74%) were managed expectantly, while 34 women (26%) were treated with immediate delivery. Time interval between admittance and delivery was 4 days longer in the expectant group (6 versus 2 days, 95%CI 2.45–5.55). Expectant management was less often associated with perinatal death than immediate delivery (50% versus 88%; OR: 0.079, 95%CI: 0.02–0.37), but no differences were found for maternal (69% versus 68%; OR: 3.1, 95%CI: 0.22–44) or neonatal complications (81% versus 80%; OR: 3.3, 95%CI: 0.068–159). In 46 reported ongoing subsequent pregnancies, 17 (37%) women had recurrent preeclampsia. While no evident trend over time can be found in management or neonatal survival over the study period, a peak appears in caesarean section rate in 2011 and the occurrence of maternal complications seem to decrease. Conclusion In women with severe, early onset preeclampsia, expectant care was often applied in the Netherlands. The maternal complication rate is high. Therefore, women need to be counselled carefully, weighing expectant care versus high perinatal mortality in case of immediate delivery. [ABSTRACT FROM AUTHOR]

Objective: Team training is frequently applied in obstetrics. We aimed to evaluate the cost-effectiveness of obstetric multi-professional team training in a medical simulation centre., Study Design: We performed a model-based cost-effectiveness analysis to evaluate four strategies for obstetric team training from a hospital perspective (no training, training without on-site repetition and training with 6 month or 3-6-9 month repetition). Data were retrieved from the TOSTI study, a randomised controlled trial evaluating team training in a medical simulation centre. We calculated the incremental cost-effectiveness ratio (ICER), which represent the costs to prevent the adverse outcome, here (1) the composite outcome of obstetric complications and (2) specifically neonatal trauma due to shoulder dystocia., Results: Mean costs of a one-day multi-professional team training in a medical simulation centre were €25,546 to train all personnel of one hospital. A single training in a medical simulation centre was less effective and more costly compared to strategies that included repetition training. Compared to no training, the ICERs to prevent a composite outcome of obstetric complications were €3432 for a single repetition training course on-site six months after the initial training and €5115 for a three monthly repetition training course on-site after the initial training during one year. When we considered neonatal trauma due to shoulder dystocia, a three monthly repetition training course on-site after the initial training had an ICER of €22,878., Conclusion: Multi-professional team training in a medical simulation centre is cost-effective in a scenario where repetition training sessions are performed on-site., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Does the effect of one-day simulation team training in obstetric emergencies decline within one year? A post-hoc analysis of a multicentre cluster randomised controlled trial. J van de Ven, AF Fransen, E Schuit, PJ van Runnard Heimel, BW Mol, SG Oei OBJECTIVE: To investigate whether the effect of a one-day simulation-based obstetric team training on patient outcome changes over time., Study Design: Post-hoc analysis of a multicentre, open, randomised controlled trial that evaluated team training in obstetrics (TOSTI study).We studied women with a singleton pregnancy beyond 24 weeks of gestation in 24 obstetric units. Included obstetric units were randomised to either a one-day, multi-professional simulation-based team training focusing on crew resource management in a medical simulation centre (12 units) or to no team training (12 units). We assessed whether outcomes differed between both groups in each of the first four quarters following the team training and compared the effect of team training over quarters. Primary outcome was a composite outcome of low Apgar score, severe postpartum haemorrhage, trauma due to shoulder dystocia, eclampsia and hypoxic-ischemic encephalopathy., Results: During a one year period after the team training the rate of obstetric complications, both on the composite level and the individual component level, did not differ between any of the quarters. For trauma due to shoulder dystocia team training led to a significant decrease in the first quarter (0.06% versus 0.26%, OR 0.19, 95% CI 0.03 to 0.98) but in the subsequent quarters no significant reductions were observed. Similar results were found for invasive treatment for severe postpartum haemorrhage where a significant increase was only seen in the first quarter (0.4% versus 0.03%, OR 19, 95% CI 2.5-147), and not thereafter., Conclusion: The beneficial effect of a one-day, simulation-based, multiprofessional, obstetric team training seems to decline after three months. If team training is further evaluated or implemented, repetitive training sessions every three months seem therefore recommended., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To describe the maternal and neonatal outcomes and prolongation of pregnancies with severe early onset pre-eclampsia before 26 weeks of gestation., Design: Nationwide case series., Setting: All Dutch tertiary perinatal care centres., Population: All women diagnosed with severe pre-eclampsia who delivered between 22 and 26 weeks of gestation in a tertiary perinatal care centre in the Netherlands, between 2008 and 2014., Methods: Women were identified through computerised hospital databases. Data were collected from medical records., Main Outcome Measures: Maternal complications [HELLP (haemolysis, elevated liver enzyme levels, and low platelet levels) syndrome, eclampsia, pulmonary oedema, cerebrovascular incidents, hepatic capsular rupture, placenta abruption, renal failure, and maternal death], neonatal survival and complications (intraventricular haemorrhage, retinopathy of prematurity, necrotising enterocolitis, bronchopulmonary dysplasia, and sepsis), and outcome of subsequent pregnancies (recurrent pre-eclampsia, premature delivery, and neonatal survival)., Results: We studied 133 women, delivering 140 children. Maternal complications occurred frequently (54%). Deterioration of HELLP syndrome during expectant care occurred in 48%, after 4 days. Median prolongation was 5 days (range: 0-25 days). Neonatal survival was poor (19%), and was worse (6.6%) if the mother was admitted before 24 weeks of gestation. Complications occurred frequently among survivors (84%). After active support, neonatal survival was comparable with the survival of spontaneous premature neonates (54%). Pre-eclampsia recurred in 31%, at a mean gestational age of 32 weeks and 6 days., Conclusions: Considering the limits of prolongation, women need to be counselled carefully, weighing the high risk for maternal complications versus limited neonatal survival and/or extreme prematurity and its sequelae. The positive prospects regarding maternal and neonatal outcome in future pregnancies can supplement counselling., Tweetable Abstract: Severe early onset pre-eclampsia comes with high maternal complication rates and poor neonatal survival., (© 2017 Royal College of Obstetricians and Gynaecologists.)