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.

Fetoscopic laser coagulation for twin-to-twin transfusion syndrome: a comparison of flexible 1.0/1.2 mm fetoscopes with curved sheaths of 2.7/3.3 mm2 vs. 2 mm fetoscopic lens technique with sheaths of 6.6/11.3 mm2.

OBJECTIVES: Fetoscopic laser coagulation of placental anastomoses is usually performed for a treatment of twin-to-twin transfusion syndrome (TTTS). A common complication of fetoscopic laser coagulation for TTTS is preterm preliminary rupture of fetal membranes (PPROM) aggravating the neonatal outcome significantly. However, use of an flexible 1 mm fetoscope with an curved sheath could reduce iatrogenic damage of the amniotic membrane and improve neonatal outcomes after laser treatment. The aim of this study was to compare neonatal outcomes using this flexible fetoscope with curved sheath vs. use of a standard lens technique. METHODS: Outcomes were retrospective analyzed after use of a standard lens fetoscope of 2 mm (sheath 6.63 mm2 or 11.27 mm2 for anterior placenta) and a flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2) in two German centers of fetal surgery, performed during 2006-2019. RESULTS: Neonatal outcome of 247 TTTS patients were analyzed including the rates of double and single fetal survival. The survival of at least one fetus was 97.2 % in the group with the ultrathin technique (n=154) compared to 88.3 % (n=93) in the group with the standard lens fetoscope (p=0.008). Survival of both fetuses was not different between groups (81.0 vs. 75.3 %). The procedure to delivery interval was significantly increased using the ultrathin fetoscope (89.1±35.0 d vs. 71.4±35.4 d, p=0.001) resulting in an increased gestational age at delivery by 11 days on average (231.9±28.1 d vs. 221.1±32.7 d, p=0.012). CONCLUSIONS: Fetal survival can be significantly increased following TTTS using flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2).

Effect of alternatively designed hospital birthing rooms on the rate of vaginal births: Multicentre randomised controlled trial Be-Up.

BACKGROUND: There is limited research into the effects of the birth environment on birth outcomes. AIM: To investigate the effect of a hospital birthing room designed to encourage mobility, self-determination and uptake of upright maternal positions in labour on the rate of vaginal births. METHODS: The multicentre randomised controlled trial Be-Up, conducted from April 2018 to May 2021 in 22 hospitals in Germany, included 3719 pregnant women with a singleton pregnancy in cephalic position at term. In the intervention birthing room, the bed was removed or covered in a corner of the room and materials were provided to promote upright maternal positions, physical mobility and self-determination. No changes were made in the control birthing room. The primary outcome was probability of vaginal births; secondary outcomes were episiotomy, perineal tears degree 3 and 4, epidural anaesthesia, "critical outcome of newborns at term", and maternal self-determination (LAS). ANALYSIS: intention-to-treat. FINDINGS: The rate of vaginal births was 89.1 % (95 % CI 87.5-90.4%; n = 1836) in the intervention group and 88.5 % (95 % CI 87.0-89.9 %; n = 1863) in the control group. The risk difference in the probability of vaginal birth was + 0.54 % (95 % CI - 1.49 % to 2.57 %), the odds ratio was 1.06 (95 % CI 0.86-1.30). Neither the secondary endpoints nor serious adverse events showed significant differences. Regardless of group assignment, there was a significant association between upright maternal body position and maternal self-determination. CONCLUSION: The increased vaginal birth rates in both comparison groups can be explained by the high motivation of the women and the staff.

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.

Treatment of Classic Mid-Trimester Preterm Premature Rupture of Membranes (PPROM) with Oligo/Anhydramnion between 22 and 26 Weeks of Gestation by Means of Continuous Amnioinfusion: Protocol of a Randomized Multicentric Prospective Controlled TRIAL and Review of the Literature.

BACKGROUND: The classic mid-trimester preterm premature rupture of membranes (PPROM) is defined as a rupture of the fetal membranes prior to 28 weeks of gestation (WG) with oligo/anhydramnion; it complicates approximately 0.4-0.7% of all pregnancies and is associated with very high neonatal mortality and morbidity. Antibiotics have limited success to prevent bacterial growth, chorioamnionitis and fetal inflammation. The repetitive amnioinfusion does not work because fluid is lost immediately after the intervention. The continuous amnioinfusion through the transabdominal port system or catheter in patients with classic PPROM shows promise by flushing out the bacteria and inflammatory components from the amniotic cavity, replacing amniotic fluid and thus prolonging the PPROM-to-delivery interval. OBJECTIVE: This multicenter trial aims to test the effect of continuous amnioinfusion on the neonatal survival without the typical major morbidities, such as severe bronchopulmonary dysplasia, intraventricular hemorrhage, cystic periventricular leukomalacia and necrotizing enterocolitis one year after the delivery. STUDY DESIGN: We plan to conduct a randomized multicenter trial with a two-arm parallel design. Randomization will be between 22/0 and 26/0 SSW. The control group: PPROM patients between 20/0 and 26/0 WG who will be treated with antibiotics and corticosteroids (from 22/0 SSW) in accordance with the guidelines of German Society of Obstetrics and Gynecology (standard PPROM therapy). In the interventional group, the standard PPROM therapy will be complemented with the Amnion Flush Method, with the amnioinfusion of Amnion Flush Solution through the intra-amnial catheter (up to 100 mL/h, 2400 mL/day). SUBJECTS: The study will include 68 patients with classic PPROM between 20/0 and 26/0 WG. TRIAL-REGISTRATION: ClinicalTrials.gov ID: NCT04696003. GERMAN CLINICAL TRIALS REGISTER: DRKS00024503, January 2021.

Maternal and neonatal outcomes of pregnancies with COVID-19 after medically assisted reproduction: results from the prospective COVID-19-Related Obstetrical and Neonatal Outcome Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus type 2 infections in pregnancy have been associated with maternal morbidity, admission to intensive care, and adverse perinatal outcomes such as preterm birth, stillbirth, and hypertensive disorders of pregnancy. It is unclear whether medically assisted reproduction additionally affects maternal and neonatal outcomes in women with COVID-19. OBJECTIVE: To evaluate the effect of medically assisted reproduction on maternal and neonatal outcomes in women with COVID-19 in pregnancy. STUDY DESIGN: A total of 1485 women with COVID-19 registered in the COVID-19 Related Obstetric and Neonatal Outcome Study (a multicentric, prospective, observational cohort study) were included. The maternal and neonatal outcomes in 65 pregnancies achieved with medically assisted reproduction and in 1420 spontaneously conceived pregnancies were compared. We used univariate und multivariate (multinomial) logistic regressions to estimate the (un)adjusted odds ratios and 95% confidence intervals for adverse outcomes. RESULTS: The incidence of COVID-19-associated adverse outcomes (eg, pneumonia, admission to intensive care, and death) was not different in women after conceptions with COVID-19 than in women after medically assisted reproduction pregnancies. Yet, the risk of obstetrical and neonatal complications was higher in pregnancies achieved through medically assisted reproduction. However, medically assisted reproduction was not the primary risk factor for adverse maternal and neonatal outcomes including pregnancy-related hypertensive disorders, gestational diabetes mellitus, cervical insufficiency, peripartum hemorrhage, cesarean delivery, preterm birth, or admission to neonatal intensive care. Maternal age, multiple pregnancies, nulliparity, body mass index >30 (before pregnancy) and multiple gestation contributed differently to the increased risks of adverse pregnancy outcomes in women with COVID-19 independent of medically assisted reproduction. CONCLUSION: Although women with COVID-19 who conceived through fertility treatment experienced a higher incidence of adverse obstetrical and neonatal complications than women with spontaneous conceptions, medically assisted reproduction was not the primary risk factor.

Hepatitis E, Schistosomiasis and Echinococcosis-Prevalence in a Cohort of Pregnant Migrants in Germany and Their Influence on Fetal Growth Restriction.

BACKGROUND: Infections, as well as adverse birth outcomes, may be more frequent in migrant women. Schistosomiasis, echinococcosis, and hepatitis E virus (HEV) seropositivity are associated with the adverse pregnancy outcomes of fetal growth restriction and premature delivery. METHODS: A cohort study of 82 pregnant women with a history of migration and corresponding delivery of newborns in Germany was conducted. RESULTS: Overall, 9% of sera tested positive for anti-HEV IgG. None of the patients tested positive for anti-HEV IgM, schistosomiasis, or echinococcus serology. Birth weights were below the 10th percentile for gestational age in 8.5% of the neonates. No association between HEV serology and fetal growth restriction (FGR) frequency was found. CONCLUSIONS: In comparison to German baseline data, no increased risk for HEV exposure or serological signs of exposure against schistosomiasis or echinococcosis could be observed in pregnant migrants. An influence of the anti-HEV serology status on fetal growth restriction could not be found.

Treatment of mid-trimester preterm premature rupture of membranes (PPROM) with multi-resistant bacteria-colonized anhydramnion with continuous amnioinfusion and meropenem: a case report and literature review.

PURPOSE: Treatment of mid-trimester classic preterm premature rupture of membranes (PPROM) with systemic antibiotics has limited success in the prevention of chorioamnionitis, funisitis and fetal inflammatory response syndrome because of very low transplacental passage. METHODS: Here we report a case of PPROM at 18 weeks gestation with anhydramnion colonized by multi-resistant Escherichia coli (E. coli). A catheter system was implanted at 23/2nd weeks gestation, enabling long-term continuous lavage of the amniotic cavity with Amnion Flush Solution (100 ml/h combined with intraamniotic meropenem application). RESULTS: The patient gave birth to a preterm male infant at 28/3rd without any signs of infection. In a follow-up examination at 24 months, there was no neurological disturbance or developmental delay. CONCLUSION: The classic PPROM with multi-resistant E. coli colonization could be treated with continuous amnioinfusion and meropenem.

Effects of the Covid-19 pandemic on maternity staff in 2020 - a scoping review.

In the spring of 2020, the SARS-CoV-2 virus caused the Covid-19 pandemic, bringing with it drastic changes and challenges for health systems and medical staff. Among the affected were obstetricians and midwives, whose close physical contact with pregnant women, women who recently gave birth, and their children was indispensable. In the obstetric setting, births cannot be postponed, and maternity staff had to adapt to assure obstetric safety while balancing evidence-based standards with the new challenges posed by the pandemic. This scoping review gives a comprehensive overview of the effecs the Covid-19 pandemic had on maternity staff. We followed the evidence-based approach described by Arksey & O'Malley: we searched several databases for English and German articles published between January 2020 and January 2021 that discussed or touched upon the effects the pandemic had on maternity staff in OECD countries and China. We found that structural challenges caused by the crisis and its subjective effects on maternity staff fell into two main topic areas. Structural challenges (the first main topic) were divided into five subtopics: staff shortages and restructuring; personal protective equipment and tests; switching to virtual communication; handling women with a positive SARS-CoV-2 infection; and excluding accompanying persons. The pandemic also strongly affected the staff's mental health (the second main topic.) Attempting to meet challenges posed by the pandemic while afraid of contamination, suffering overwork and exhaustion, and struggling to resolve ethical-moral dilemmas had severe negative subjective effects. Several studies indicated increased depression, anxiety, stress levels, and risk of post-traumatic stress symptoms, although the crisis also generated strong occupational solidarity. Care for pregnant, birthing, and breast-feeding women cannot be interrupted, even during a pandemic crisis that requires social distancing. Maternity staff sometimes had to abandon normal standards of obstetric care and were confronted with enormous challenges and structural adjustments that did not leave them unscathed: their mental health suffered considerably. Researchers should study maternity staff's experiences during the pandemic to prepare recommendations that will protect staff during future epidemics.

Lower Spermatozoal PIWI-LIKE 1 and 2 Transcript Levels Are Significantly Associated with Higher Fertilization Rates in IVF.

The four human PIWI-LIKE gene family members PIWI-LIKE 1-4 play a pivotal role in stem cell maintenance and transposon repression in the human germline. Therefore, dysregulation of these genes negatively influences the genetic stability of the respective germ cell and subsequent development and maturation. Recently, we demonstrated that a lower PIWI-LIKE 2 mRNA expression in ejaculated spermatozoa is more frequent in men with oligozoospermia. In this study, we analysed how PIWI-LIKE 1-4 mRNA expression in ejaculated spermatozoa predicts ART outcome. From 160 IVF or ICSI cycles, portions of swim-up spermatozoa used for fertilization were collected, and the total RNA was isolated. PIWI-LIKE 1-4 mRNA expression was measured by qPCR using TaqMan probes with GAPDH as a reference gene. PIWI-LIKE 1 and 2 transcript levels in the spermatozoa of the swim-up fraction were positively correlated to each other (rS = 0.78; p < 0.001). Moreover, lower PIWI-LIKE 2 mRNA levels, as well as lower PIWI-LIKE 1 mRNA levels, in these spermatozoa were positively associated with a fertilization rate ≥ 50% in the respective ART cycles (p = 0.02 and p = 0.0499, Mann-Whitney U-Test). When separately analysing IVF and ICSI cycles, PIWI-LIKE 1 and 2 transcript levels were only significantly associated to increased fertilization rates in IVF, yet not in ICSI cycles. Spermatozoal PIWI-LIKE 3 and 4 transcript levels were not significantly associated to fertilization rates in ART cycles. In conclusion, lower levels of spermatozoal PIWI-LIKE 1 and 2 mRNA levels are positively associated with a higher fertilization rate in IVF cycles.

Cardiovascular Risk Reduction in Women Following Hypertensive Disorders of Pregnancy - a Prospective, Randomised, Controlled Interventional Study.

Background Women have a markedly increased lifetime risk for cardiovascular morbidity and mortality following hypertensive disorders of pregnancy. Arterial stiffness is regarded as a target parameter for reducing cardiovascular risk and can be modified by lifestyle changes. Methods In a prospective, randomised, controlled interventional study, starting 6 weeks postpartum, the effect of nutritional intervention combined with an intensive 6-month cardiovascular exercise programme on arterial stiffness was investigated by means of pulse wave velocity (PWV) in 38 women with severe hypertensive disorder of pregnancy (preeclampsia with or without pre-existing hypertension and/or HELLP syndrome). A reference group was formed with postpartum women without pregnancy complications or known cardiovascular risk and the arterial stiffness was studied by means of PWV at the time of delivery. The PWV was measured in the intervention and control groups within a week after delivery and after 32 weeks (6 weeks + 6 months). A feasibility analysis was performed in addition. Results 29 of 38 women with severe hypertensive disorder of pregnancy and 38 postpartum women in the reference group were included in the analysis (intervention group n = 14; control group n = 15; reference group n = 38). Adherence to a) the nutritional counselling and b) the intensive cardiovascular exercise programme was 73% and 79% respectively. A clinically significant difference (d = 0.65) in pulse wave velocity between the intervention and control groups was found after 6 months (6.36 ± 0.76 vs. 7.33 ± 2.25 m/s; group × time: p = 0.632). The PWV of the intervention group corresponded to that of the reference group at the end of the study (6.36 ± 0.76 m/s vs. 6.5 ± 0.70; d = 0.19), while the results in the control group differed markedly from this (7.33 ± 2.25 m/s; d = 0.56). Conclusion The study documents the feasibility of lifestyle intervention with physical exercise after delivery (starting 6 weeks postpartum). The intervention showed a significant clinical effect by reducing arterial stiffness to the level of the reference group. Before this intervention can be included in the standard of care and prevention, follow-up studies must confirm these results and the medium-term effects on cardiovascular risk.

[Herpes Simplex Virus Infection in Two Premature Infants - Diagnostic and Therapeutic Management]. / Infektion durch Herpes simplex Virus bei zwei unreifen Frühgeborenen ­ Diagnostisches und therapeutisches Management.

Herpes simplex virus type 1 or 2 (HSV 1/2)-related infections in neonates are rare but associated with high morbidity and mortality, especially if specific treatment is delayed. Due to immaturity of the immunological system, premature infants are particularly at risk. In addition, symptoms of neonatal HSV infections may imitate prematurity-related problems, such as sepsis. So, a thorough patient's history and appropriate diagnostic measures are important to confirm the diagnosis. We present 2 premature infants with systemic HSV infections and discuss diagnostic and therapeutic management. Both were treated with intravenous acyclovir followed by enteral aciclovir suppressive therapy.

Daily monitoring of vaginal interleukin 6 as a predictor of intraamniotic inflammation after preterm premature rupture of membranes - a new method of sampling studied in a prospective multicenter trial.

OBJECTIVES: (A) To introduce a new technique for vaginal fluid sampling (biocompatible synthetic fiber sponge) and (B) evaluate the collected vaginal fluid interleukine-6 (IL-6vag)-concentration as a new diagnostic tool for daily monitoring of intrauterine inflammation after preterm premature rupture of membranes (PPROM). Secondary objectives were to compare the potential to predict an intrauterine inflammation with established inflammation parameters (e.g., maternal white blood cell count). METHODS: This prospective clinical case-control diagnostic accuracy multicenter study was performed with women after PPROM (gestational age 24.0/7 - 34.0/7 weeks). Sampling of vaginal fluid was performed once daily. IL-6vag was determined by electrochemiluminescence-immunoassay-kit. Neonatal outcome and placental histology results were used to retrospectively allocate the cohort into two subgroups: 1) inflammation and 2) no inflammation (controls). RESULTS: A total of 37 cases were included in the final analysis. (A): Measurement of IL-6 was successful in 86% of 172 vaginal fluid samples. (B): Median concentration of IL-6vag in the last vaginal fluid sample before delivery was significantly higher within the inflammation group (17,085 pg/mL) compared to the controls (1,888 pg/mL; p=0.01). By Youden's index an optimal cut-off for prediction an intrauterine inflammation was: 6,417 pg/mL. Two days before delivery, in contrast to all other parameters IL-6vag remained the only parameter with a sufficient AUC of 0.877, p<0.001, 95%CI [0.670-1.000]. CONCLUSIONS: This study established a new technique for vaginal fluid sampling, which permits assessment of IL-6vag concentration noninvasively in clinical daily routine monitoring.

Fetal growth restriction in a cohort of migrants in Germany.

BACKGROUND: Migrant women may have an increased risk of adverse birth outcomes. This study analyses the occurrence of low birth weight, preterm birth and intrauterine growth restriction / fetal growth restriction (IUGR/FGR) in pregnant migrants. METHOD: Cross-sectional study of 82 mother-child pairs of pregnant migrants attending medical care in Germany. RESULTS: The Median age was 27 years, 49% of patients were of oriental-asian ethnicity and median year of migration was 2015. At least one previous pregnancy was reported in 76% of patients, in 40% the delivery mode was caesarian section. Median gestational age was 39.7 weeks. Preterm birth occurred in 6.1% of pregnancies. Median gestational age for preterm birth was 32.3 weeks. Low birth weight (< 2500 g) occurred in 6.1%. Birth weights below the 10th percentile of birth weight for gestational age were observed in 8.5% of the total cohort. CONCLUSIONS: Compared to German data no increased occurrence of low birth weight, preterm birth or IUGR/FGR was found. We note that the rate of caesarian section births was higher than in the general population for reasons yet to be identified. The authors propose stratification according to migration status for the national documentation of birth outcomes in Germany.

[Reduction of Visitor- and Staff-Associated Risk of Infection by Complex Intervention in the Department of Feto-Maternal Medicine]. / Reduktion des Besucher- und Personal- assoziierten Infektionsrisikos durch komplexe Intervention auf perinatologischen Stationen.

AIM: Clinical trial registration of this trial: is to demonstrate in a department of feto-maternal medicine: (a) that a complex intervention improves hand hygiene of visitors, siblings and staff; and (b) that automated voice prompts at disinfectant dispensers improve rate of hand disinfection. STUDY DESIGN: (a) Pre-/post-test follow-up design with control (1-12/2016), intervention (1-12/2017), follow-up-period (1/2018-12/2019); and (b) RCT in quasi crossover design. Primary endpoints: (a) disinfectant consumption (DC) per patient-day, and (b) DC at disinfectant dispenser per passer-by. RESULTS: A multimodal strategy within the intervention period showed a relevant positive effect on hand hygiene compliance (in IP: 26.2% more DC; p=0.088). Voice prompts increased DC by 28.6% (p=0.025). The odds ratio for high positive fingertip testing plates of visiting children (siblings) between control and intervention period was 0.35 (95% CI [0.1074-0.9708] p=0.039). CONCLUSION: Complex intervention and electronic voice prompts on disinfectant dispensers improve hand hygiene behaviour in perinatology. Installation of disinfectant dispensers in a child-friendly position and adequate information material appeal to children. The data represent an important contribution to improve hand hygiene of visitors, siblings and staff in hospitals in a pandemic situation.

Effects of the birthing room environment on vaginal births and client-centred outcomes for women at term planning a vaginal birth: BE-UP, a multicentre randomised controlled trial.

BACKGROUND: Caesarean sections (CSs) are associated with increased risk for maternal morbidity and mortality. The recommendations of the recently published German national health goal 'Health in Childbirth' (Gesundheit rund um die Geburt) promote vaginal births (VBs). This randomised controlled trial (RCT) evaluates the effects of a complex intervention pertaining to the birth environment, based on the sociology of technical artefacts and symbolic interactionism. The intervention is intended to foster an upright position and mobility during labour, which lead to a higher probability of VB. METHODS/DESIGN: This study is an active controlled superiority trial with a two-arm parallel design. The complex intervention involves making changes to the birthing room to encourage an upright position and mobility of women in labour and to relax them, which may help them to cope with labour and may increase self-determination. This may result in more VBs. Included in the study are primiparae and multiparae with a singleton foetus in cephalic presentation at term planning a VB. According to the sample size calculation, 3800 women in 12 obstetrical units are to be included. Randomisation will be performed centrally and controlled by an independent coordination centre. Blinding of participants and staff is not possible. Key outcomes are VB, episiotomy, perineal tears, epidural analgesia, critical outcome of newborn at term and maternal self-determination during birth. Additionally, a health economic evaluation will be performed. DISCUSSION: This is the first adequately powered multicentre RCT examining the effect of a redesigned birthing room on the probability of a VB and patient-centred physical and emotional outcomes. An increase in the number of VBs by 5% from a baseline of 74% to 79% would result in 21,000 women per year experiencing a VB rather than a CS in Germany. Expected benefits are greater self-determination during labour, improved physical and emotional client-centred outcomes, fewer medical interventions and a reduction in health-care costs. TRIAL REGISTRATION: German Clinical Trials Register (Deutsches Register Klinischer Studien), DRKS00012854 . Registered on 7 March 2018.

Technique of sonographic assessment of lower uterine segment in women with previous cesarean delivery: a prospective, pre/intraoperative comparative ultrasound study.

OBJECTIVE: The purpose of this study was: (A) to establish the effects of different ultrasound measurement methods (linear versus curved array) and measuring conditions [impact of pressure by fetal head/pelvis on the lower uterine segment (LUS)] during LUS-muscular-thickness measurement, (B) to introduce the intraoperative ultrasound measurement of LUS-muscular thickness (reference measurement method), and (C) to evaluate the correlation between different combinations of LUS-muscular-thickness measurement ultrasound techniques at birth planning and preoperative versus intraoperative measurements. METHODS: A prospective clinical observational study of women with the previous cesarean delivery was conducted. LUS-muscular thickness was measured: first at birth planning and second preoperatively using linear and curved probes (transabdominal) and an endocavitar probe (transvaginal), examined with and without pressure by fetal head/pelvis on LUS during measurement and third intraoperatively during repeat cesarean. Bland-Altman plots, paired t tests, Pearson's correlation coefficient, and scatter plots were used. RESULTS: Thirty-three women were included in the study (ultrasound measurements: n = 601). There was no systematic difference between LUS-muscular-thickness measurements with linear versus curved array (mean difference = 0.06 mm; p = 0.24; nm = 133) but between measurements with pressure by the fetus versus without (mean difference = - 0.37 mm; p < 0.001; nm = 243). The highest correlation coefficients were detected for the preoperative (at the day of cesarean section), transabdominal-vaginal approach combined ultrasound measurements versus the intraoperative ultrasound measurements of LUS-muscular thickness-as long as the measurements were made without pressure from the fetal head/pelvis on the LUS [0.86, p < 0.001, n = 24, 95% CI (0.70, 0.94)]. CONCLUSIONS: The systematic application of predetermined measuring conditions, standardized setup criteria improves the performance of LUS thickness measurement by ultrasound near term. CLINICALTRIALS. GOV IDENTIFIER: NCT02827604.

Ultrasound elastography of the lower uterine segment in women with a previous cesarean section: Comparison of in-/ex-vivo elastography versus tensile-stress-strain-rupture analysis.

OBJECTIVES: The purpose of this study was to assess, if the biomechanical properties of the lower uterine segment (LUS) in women with a previous cesarean section (CS) can be determined by ultrasound (US) elastography. The first aim was to establish an ex-vivo LUS tensile-stress-strain-rupture(break point) analysis with the possibility of simultaneously using US elastography. The second aim was to investigate the relationship between measurement results of LUS stiffness using US elastography in-/ex-vivo with results of tensile-stress-strain-rupture analysis, and to compare different US elastography LUS-stiffness-measurement methods ex-vivo. STUDY DESIGN: An explorative experimental, in-/ex-vivo US study of women with previous CS was conducted. LUS elasticity was measured by point Shear Wave Elastography (pSWE) and bidimensional Shear-Wave-Elastography (2D-SWE) first in-vivo during preoperative examination within 24 h before repeat CS (including resection of the thinnest part of the LUS = uterine scar area during CS), second within 1 h after operation during the ex-vivo experiment, followed by tensile-stress-strain-rupture analysis. Pearson's correlation coefficient and scatter plots, Bland-Altman plots and paired T-tests, were used. RESULTS: Thirty three women were included in the study; elastography measurements n = 1412. The feasibility of ex-vivo assessment of LUS by quantitative US elastography using pSWE and 2D-SWE to detect stiffness of LUS was demonstrated. The strongest correlation with tensile-stress-strain analysis was found in the US elastography examination carried out with 2D-SWE (0.78, p < 0.001, 95%CI [0.48, 0.92]). The laboratory experiment illustrated that, the break point - as a surrogate marker for the risk of rupture of the LUS after CS - is linearly dependent on the thickness of the LUS in the scar area (Coefficient of correlation: 0.79, p < 0.001, 95%CI [0.55, 0.91]). Two extremely stiff LUS-specimens (outlier or extreme values) rupture even at less stroke/strain than would be expected by their thickness. CONCLUSION: This study confirms that US elastography can help in determining viscoelastic properties of the LUS in women with a previous CS. The data from our small series are promising. However whether individual extreme values of high stiffness and consecutive restricted biomechanical resilience can explain the phenomenon of rupture during TOLAC in cases of LUS with adequate thickness remains a question which prospective trials have to analyze before US elastography can be introduced into clinical practice.

Hyperbaric oxygenation and glucose/amino acids substitution in human severe placental insufficiency.

In the first case, the AA and glucose were infused through a perinatal port system into the umbilical vein at 30 weeks' gestation due to severe IUGR. The patient received daily hyperbaric oxygenation (HBO, 100% O2 ) with 1.4 atmospheres absolute for 50 min for 7 days. At 31+4  weeks' gestation, the patient gave birth spontaneously to a newborn weighing 1378 g, pH 7.33, APGAR score 4/6/intubation. In follow-up examinations at 5 years of age, the boy was doing well without any neurological disturbance or developmental delay. In the second case, the patient presented at 25/5  weeks' gestation suffering from severe IUGR received HBO and maternal AA infusions. The cardiotocography was monitored continuously during HBO treatment. The short-time variations improved during HBO from 2.9 to 9 msec. The patient developed pathologic CTG and uterine contractions 1 day later and gave birth to a hypotrophic newborn weighing 420 g. After initial adequate stabilization, the extremely preterm newborn unfortunately died 6 days later. Fetal nutrition combined with HBO is technically possible and may allow the prolongation of the pregnancy. Fetal-specific amino-acid composition would facilitate the treatment options of IUGR fetuses and extremely preterm newborn.

Does ultrasound-guided intervention during repeat cesarean sections improve uterine scar architecture and reduce the number of scars? A prospective controlled clinical intervention trial.

Purpose To evaluate whether intraoperative ultrasound-guided detection and resection of the uterine scar during repeat/second cesarean can reduce the number of scars and improve uterine scar architecture. Materials and methods A prospective controlled clinical intervention trial was performed with the following groups: control group 1 (CS1-G): first cesarean; control group 2 (CS2-G): second cesarean utilizing the usual procedure and intervention group (Int-G): repeat/second cesarean with intervention. Transvaginal ultrasound scans were performed 6-9 months after each cesarean. Both primary (double scarring rate) and secondary outcomes [deficiency ratio=d/(b+d)] were analyzed. The deficiency ratio describes the thinning of the remaining myometrium (d=residual myometrial thickness) over the "apparent" defect (b=scar depth). Results In total, 124 of the 156 recruited women were examined, eight were excluded from analysis. The double scarring rate decreased from 42.9% (12/28) in CS2-G to 7.1% (2/28) in the Int-G [difference: 35.8%; 95% confidence interval (CI) (13.2, 54.5); P=0.002]. Two-way analysis of variance (ANOVA) revealed a significant difference between CS2-G and the Int-G in the deficiency ratio adjusted for elective/primary cesareans, with thicker remaining myometrium over the scar defect in the Int-G [difference: -0.24; 95% CI (-0.34, -0.15); P<0.001]. Conclusion Ultrasound-guided resection of the uterine scar area during repeat cesareans reduces the scarring rate and improves thickness of the remaining myometrium as detected by ultrasonography 6-9 months postoperatively.