Pentaerythrityl tetranitrate improves the outcome of children born to mothers with compromised uterine perfusion-12-months follow-up and safety data of the double-blind randomized PETN trial.

BACKGROUND: This is a follow-up study to the pentaerythrityl tetranitrate randomized controlled multicenter trial that reports neonatal outcome data of newborns admitted to neonatal intensive care units and outcome data of the offspring at 12 months of age. OBJECTIVE: We present data on adverse events reported during the study to document the safety of pentaerythrityl tetranitrate treatment during pregnancy. To further evaluate the effects of pentaerythrityl tetranitrate on neonatal and long-term outcomes, we present follow up data from of 240 children at 12 months of age, including information on height, weight, head circumference, developmental milestones, and the presence of chronic disease and of 144 newborns admitted to the neonatal intensive care unit during the trial. STUDY DESIGN: The pentaerythrityl tetranitrate trial was a randomized, double-blind, placebo-controlled study designed to assess the efficacy and safety of the nitric oxide-donor pentaerythrityl tetranitrate in the prevention of fetal growth restriction and perinatal death in pregnancies complicated by abnormal placental perfusion. RESULTS: Results at 12 months demonstrated that significantly more children were age appropriately developed without impairments in the pentaerythrityl tetranitrate group (P=.018). In addition, the presence of chronic disease was lower in the pentaerythrityl tetranitrate group (P=.041). Outcome data of the 144 newborns admitted to the neonatal intensive care unit did not reveal differences between the treatment and placebo groups. There were no differences in the number or nature of reported adverse events between the study groups. CONCLUSION: The analysis shows that study children born in the pentaerythrityl tetranitrate cohort have a clear advantage compared with the placebo group at the age of 12 months, as evidenced by the increased incidence of normal development without the presence of chronic disease. Although safety has been proven, further follow-up studies are necessary to justify pentaerythrityl tetranitrate treatment during pregnancies complicated by impaired uterine perfusion.

Intrauterine Growth Restriction: Need to Improve Diagnostic Accuracy and Evidence for a Key Role of Oxidative Stress in Neonatal and Long-Term Sequelae.

Intrauterine growth restriction (IUGR) and being small for gestational age (SGA) are two distinct conditions with different implications for short- and long-term child development. SGA is present if the estimated fetal or birth weight is below the tenth percentile. IUGR can be identified by additional abnormalities (pathological Doppler sonography, oligohydramnion, lack of growth in the interval, estimated weight below the third percentile) and can also be present in fetuses and neonates with weights above the tenth percentile. There is a need to differentiate between IUGR and SGA whenever possible, as IUGR in particular is associated with greater perinatal morbidity, prematurity and mortality, as well as an increased risk for diseases in later life. Recognizing fetuses and newborns being "at risk" in order to monitor them accordingly and deliver them in good time, as well as to provide adequate follow up care to ameliorate adverse sequelae is still challenging. This review article discusses approaches to differentiate IUGR from SGA and further increase diagnostic accuracy. Since adverse prenatal influences increase but individually optimized further child development decreases the risk of later diseases, we also discuss the need for interdisciplinary follow-up strategies during childhood. Moreover, we present current concepts of pathophysiology, with a focus on oxidative stress and consecutive inflammatory and metabolic changes as key molecular mechanisms of adverse sequelae, and look at future scientific opportunities and challenges. Most importantly, awareness needs to be raised that pre- and postnatal care of IUGR neonates should be regarded as a continuum.

[Acute Fatty Liver of Pregnancy - Case Series]. / Akute Schwangerschaftsfettleber ­ Fallserie einer seltenen Schwangerschaftskomplikation.

With a prevalence of 0,01-0,03%, acute fatty liver in pregnancy (AFLP) is a rare and dangerous complication of pregnancy and is difficult to distinguish from other, sometimes more common, pregnancy diseases such as HELLP syndrome, aHUS and TTP because of its mostly non-specific symptoms. Due to its rarity, AFLP is often not obvious to the obstetrician as a possible differential diagnosis. Yet early diagnosis and the fastest possible delivery is the only causal therapy and is important for the mortality rate. In the present manuscript, the pathophysiology, diagnosis and therapy of acute fatty liver in pregnancy are highlighted for the clinical routine based on case descriptions from three university hospitals, and reference is made to possible findings that are helpful in establishing the diagnosis. The angiogenic preeclampsia marker sFlt-1 plays a role and provides new opportunities to consider pathophysiological approaches.

[Birth in the Midwife-Led Delivery Room of a Perinatal Center - Learning Curve, Outcomes and Benchmark]. / Geburt im hebammengeleiteten Kreißsaal eines Perinatalzentrums ­ Lernkurve, Ergebnisse und Benchmark.

INTRODUCTION: Most births in Germany take place in a clinical setting. Midwife-led units have been offered in Germany since 2003 as an addition to the primarily physician-led obstetric care. The purpose of this study was to analyze differences regarding medical parameters between a midwife-led and a primarily physician-led unit in a level 1 perinatal center. MATERIAL AND METHODS: Between 12/2020 and 12/2021, all births begun in the midwife-led unit were retrospectively analyzed and compared to a physician-led control cohort. Outcome measures were defined as obstetric interventions, delivery mode and duration, delivery position, and maternal and neonatal outcome. RESULTS: The percentage of deliveries started in the midwife-led unit out of the total birth rate was 4.8% (n=132). Most transfers were made for more effective analgesia (52.6%). Among medically indicated transfers (n=30, 39.5%), transfers due to CTG abnormalities and failure to progress in labor after rupture of membranes predominated. 43.9% (n=58) of patients gave birth successfully in the midwife-led unit. The rate of episiotomy was significantly higher in the primarily physician-led unit compared to the successful midwife-led unit (p=0.019). CONCLUSION: Birth in a midwife-led unit within a perinatal center can be considered an equivalent alternative to primarily physician-led birth for low-risk pregnant women.

Interteam PERINAT - interprofessional team collaboration in undergraduate midwifery and medical education in the context of obstetric emergencies: Presentation of simulation scenarios and empirical evaluation results.

To promote the expansion of interprofessional training objectives in the curriculum of health professions curriculum at the Medical Faculty, University of Leipzig, the interprofessional teaching project between the Department of Obstetrics, the Skills and Simulation Centre and the School of Midwifery was selected to promote innovative teaching projects, supported by the University of Leipzig [https://www.stil.uni-leipzig.de/] grant "StiL - Studying in Leipzig". Using scenarios with simulated patients, students were to recall and apply theoretically learned procedures and immediate measures in an obstetric emergency under supervision and to communicate these clearly in the team. Final-year medical students from the Medical Faculty (n=15) and midwifery students (n=17) from the vocational school went through teaching situations together, in which two simulation scenarios (shoulder dystocia and postpartum haemorrhage) were implemented. The aim of the project was to integrate interprofessional collaboration into training and to learn together under simulated conditions in the Skills and Simulation Center protected environment. The following questions was intended to be clarified in the project in addition to the establishment of a sub-professional teaching unit What do students benefit most from in interprofessional teaching units? Are there differences between midwifery and medical students? Is the learning success the same for team-communicative and professional learning goals? To clarify the questions, an evaluation was carried out using an exploratory questionnaire with a Likert scale. All students particularly liked the exchange and contact with other professional groups, the communicative aspect and situational action in unforeseen emergency situations. The participants stated that they had benefited from both interprofessional teaching units, in terms of team communication as well as in professional terms. However, medical students experienced significantly higher cognitive overload regarding prior acquired knowledge compared to vocational midwifery students. Overall, the team communication learning objectives were more difficult to fulfill.

Effect of pentaerythritol tetranitrate (PETN) on the development of fetal growth restriction in pregnancies with impaired uteroplacental perfusion at midgestation-a randomized trial.

BACKGROUND: Fetal growth restriction is strongly associated with impaired placentation and abnormal uteroplacental blood flow. Nitric oxide donors such as pentaerythritol tetranitrate are strong vasodilators and protect the endothelium. Recently, we demonstrated in a randomized controlled pilot study a 38% relative risk reduction for the development of fetal growth restriction or perinatal death following administration of pentaerythritol tetranitrate to pregnant women at risk, identified by impaired uterine perfusion at midgestation. Results of this monocenter study prompted the hypothesis that pentaerythritol tetranitrate might have an effect in pregnancies with compromised placental function as a secondary prophylaxis. OBJECTIVE: This study aimed to test the hypothesis that the nitric oxide donor pentaerythritol tetranitrate reduces fetal growth restriction and perinatal death in pregnant women with impaired placental perfusion at midgestation in a multicenter trial. STUDY DESIGN: In this multicenter, randomized, double-blind, placebo-controlled trial, 2 parallel groups of pregnant women presenting with a mean uterine artery pulsatility index >95th percentile at 19+0 to 22+6 weeks of gestation were randomized to 50-mg Pentalong or placebo twice daily. Participants were assigned to high- or low-risk groups according to their medical history before randomization was performed block-wise with a fixed block length stratified by center and risk group. The primary efficacy endpoint was the composite outcome of perinatal death or development of fetal growth restriction. Secondary endpoints were neonatal and maternal outcome parameters. RESULTS: Between August 2017 and March 2020, 317 participants were included in the study and 307 were analyzed. The cumulative incidence of the primary outcome was 41.1% in the pentaerythritol tetranitrate group and 45.5% in the placebo group (unadjusted relative risk, 0.90; 95% confidence interval, 0.69-1.17; adjusted relative risk, 0.90; 95% confidence interval, 0.69-1.17; P=.43). Secondary outcomes such as preterm birth (unadjusted relative risk, 0.73; 95% confidence interval, 0.56-0.94; adjusted relative risk, 0.73; 95% confidence interval, 0.56-0.94; P=.01) and pregnancy-induced hypertension (unadjusted relative risk, 0.65; 95% confidence interval, 0.46-0.93; adjusted relative risk, 0.65; 95% confidence interval, 0.46-0.92; P=0.01) were reduced. CONCLUSION: Our study failed to show an impact of pentaerythritol tetranitrate on the development of fetal growth restriction and perinatal death in pregnant women with impaired uterine perfusion at midgestation. Pentaerythritol tetranitrate significantly reduced secondary outcome parameters such as the incidence of preterm birth and pregnancy-induced hypertension in these pregnancies.

Diseases and complications of the puerperium.

BACKGROUND: In terms of maternal morbidity and mortality, the puerperium is just as significant as pregnancy and childbirth. Nearly half of all maternal deaths occur in the time after delivery. METHODS: This review is based on pertinent articles in English and German from the years 2000- 2020 that were retrieved by a selective search in MEDLINE and EMBASE, as well as on the available guidelines in English and German and on German-language textbooks of obstetrics. RESULTS: The most common and severe complications are, in the post-placental phase, bleeding and disturbances of uterine involution; in the first seven days after delivery, infection (e.g., endomyometritis, which occurs after 1.6% [0.9; 2.5] of all births) and hypertension-related conditions. Thromboembolism, incontinence and disorders of the pelvic floor, mental disease, and endocrine disturbances can arise at any time during the puerperium. In an Australian study, the incidence of embolism was 0.45 per 1000 births, with 61.3% arising exclusively after delivery. CONCLUSION: Basic familiarity with the most common and severe diseases in the puerperium is important for non-gynecologists as well, among other things because highly acute, lifethreatening complications can arise that demand urgent intervention.