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.

Course of an unplanned and unexpected pregnancy in a 39 year-old patient with Complex bladder extrophy: a case report.

BACKGROUND: With improved operative techniques pregnancy rates have been rising in patients with anomalies of the extrophy-epispadias-complex, including also female patients with bladder extrophy. Specific risks around pregnancy need to be addressed sufficiently beforehand. CASE PRESENTATION: An unplanned pregnancy was detected at 34 weeks in a 39-year old White female patient with former complex bladder extrophy. Decades after her operation she had not received any follow-up medical care and believed to be unable to conceive due to her anomaly. Thus no contraceptive matters were taken. The patient had lived in a stable relationship with regular sexual intercourse for many years. Until 34 weeks the pregnancy was uncomplicated, but then uterine prolapse and signs of beginning pre-eclampsia appeared, and a healthy girl was born with cesarean section. CONCLUSION: As patients with bladder extrophy and other anomalies from the extrophy-epispadias-complex reach adolescence/adulthood, they need continuous medical follow-up and transition of care to adult surgery and gynecology in order to address specific aspects of sexual health, reproduction, contraception, and also cancer screening. In the presented case lack of transition of care resulted in an unplanned and complicated pregnancy.

Association between TGFß1 Levels in Cord Blood and Weight Progress in the First Year of Life.

Transforming growth factor beta-1 (TGFß1) is an adipokine secreted from adipose tissue, placental tissue and immune cells with a role in cell proliferation, cell apoptosis and angiogenic proliferation. The role of TGFß1 in pregnancy and child growth and the source of cord TGFß1 are yet unknown. In this study, we sought to clarify the correlation of TGFß1 levels with parameters of intrauterine growth and child growth during the first year of life, and to determine whether their source is primarily of fetal or maternal origin. Serum samples and anthropometric measurements were obtained from the LIFE Child cohort of 79 healthy mother-child pairs. Measurements were conducted using enzyme-linked immunosorbent assays. Statistical analyses including Mann-Whitney U-test, correlation analyses and linear regression analyses were performed using GraphPad Prism and R. TGFß1 levels were significantly higher in cord than in maternal serum, suggesting a fetal origin. Multivariate regression analyses revealed strong positive associations between cord TGFß1 levels at birth and child weight at U6. Furthermore, cord TGFß1 was significantly correlated with child weight at approximately one year of age. An increase of 10,000 pg/mL in cord TGFß1 concentrations at birth was associated with a higher body weight of 201 g at roughly one year of age when adjusted for sex.

Adipokines in Pregnancy: A Systematic Review of Clinical Data.

Adipokines are signaling proteins involved in metabolic, endocrinological, vascular and immunogenic processes. Associations of various adipokines with not only insulin resistance but also with increased insulin sensitivity, increased systolic blood pressure, and atherosclerosis highlight the significance of adipokines in several components of metabolic syndrome and metabolic diseases in general. As pregnancy presents a unique metabolic state, the role of adipokines in pregnancy, and even in various pregnancy complications, appears to be key to elucidating these metabolic processes. Many studies in recent years have attempted to clarify the role of adipokines in pregnancy and gestational pathologies. In this review, we aim to investigate the changes in maternal adipokine levels in physiological gestation, as well as the association of adipokines with pregnancy pathologies, such as gestational diabetes mellitus (GDM) and preeclampsia (PE). Furthermore, we will analyze the association of adipokines in both maternal serum and cord blood with parameters of intrauterine growth and various pregnancy outcomes.

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.

Adipocyte Fatty Acid-Binding Protein 4 is Altered in Growth Discordant Dichorionic, but not in Monochorionic Twins.

CONTEXT: The fetal period has a critical and long-lasting impact on the regulation of metabolic processes and a life-long predisposition for obesity and metabolic syndrome. The exact mechanisms are unknown, but epigenetic regulation likely plays a major role. Twins represent an excellent model to study these mechanisms, as they share the same intrauterine environment and similar or even the same genetic information. We examined cord blood levels of adipocyte fatty-acid binding protein 4 (A-FABP or FABP4), a novel adipokine correlated with obesity and metabolic disease in children and adults. OBJECTIVE: To examine A-FABP levels in the cord blood of twins with concordant and discordant growth and in singletons with intrauterine growth restriction (IUGR). DESIGN: Cohort study of 36 twin pairs (25 growth concordant and 11 growth discordant), and 42 singleton pregnancies (28 IUGR and 13 normally grown controls, 1 HELLP). OUTCOME MEASURES: Cord blood A-FABP levels measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: A-FABP levels were higher in the smaller of growth discordant dichorionic (DC) twins versus their co-twins (109.46 ±â€…62.80 ng/mL vs. 72.93 ±â€…36.66 ng/mL, P = 0.028). A-FABP was negatively correlated with birth weight and gestational age (P < 0.001), but not with birth weight z-score (P = 0.37). CONCLUSIONS: Increased A-FABP levels might be associated with an increased metabolic risk in growth-restricted (twins) and prematurely born infants.

[Does Lower Uterine Segment Thickness Measurement Improve Birth Planning After Previous Cesarean Section?] / Verbessert die Diagnostik des unteren Uterinsegments die Geburtsplanung bei Status nach Sectio?

INTRODUCTION: Lower uterine segment (LUS) thickness measurement is frequently used to select patients for trial of labor after a previous cesarean section (TOLAC). To date no significant benefit of LUS measurement has ever been proven, and no standard protocol or clear cut-off value exists. The aim of this study was to evaluate the benefit of LUS measurement in a daily routine setting. MATERIAL AND METHODS: In this retrospective study, we evaluated 631 pregnancies after previous cesarean section (CS). Ultrasound measurements of myometrial (mLUS) and/or full LUS (fLUS) thickness were performed in 399 (63%) patients. The incidence, time, and mode of detection of uterine defects were studied. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated for different cut-off values of LUS thickness. RESULTS: Uterine defects were diagnosed in 28 (4.4%) patients. Detection rate of ultrasound was low (13.6%), with better sensitivity, specificity, PPV, and NPV at lower (2 mm (fLUS) / 1 mm (mLUS): 75/96/48.3/98.7%) than at higher cut-off values (3 mm (fLUS) / 2 mm (mLUS): 15.8/93.2/10.4/68.7%). DISCUSSION: The benefit of LUS thickness measurement appears overestimated. As a large number of methodological factors trigger inaccuracy, a consistent protocol including both a transabdominal and a transvaginal scan performed by a trained examiner might improve accuracy. Exclusion of uterine defects might be more useful for prenatal selection after CS.

Cesarean section scar in 3 T magnetic resonance imaging and ultrasound: image characteristics and comparison of the methods.

PURPOSE: Uterine rupture during labor is a rare but life-threatening complication after previous cesarean section (CS). Prenatal risk is assessed using ultrasound thickness measurement of the lower uterine segment (LUS). Due to inhomogeneous study results, however, clinical obstetrics still lacks for standard protocols and reliable reference values. As 3 T magnetic resonance imaging (MRI) has not yet been sufficiently studied regarding LUS diagnostics after previous CS, we sought to evaluate its feasibility focusing on thickness measurements and typical characteristics of the CS-scar region in comparison to ultrasound and the intraoperative status. METHODS: In this prospective study, 25 asymptomatic patients with one previous CS and inconspicuous ultrasound findings were included. An additional 3 T MRI with either a T2-weighted Turbo-Spin-Echo or a Half Fourier-Acquired-Single-shot-Turbo-spin-Echo sequence in a sagittal orientation was performed. We analyzed categorical image quality, inter- and intra-rater reliability as well as anatomy, morphology and thickness of the LUS. Results were compared to ultrasound and intraoperative findings. RESULTS: MRI provided good to excellent image quality in all patients. The imaged structures presented with a high variability in anatomy and morphology. Image characteristics indicating the uterine scar were only found in 11/25 (44%) patients. LUS thickness measurements with MRI showed good inter- and intra-rater reliability but poor agreement with ultrasound. CONCLUSIONS: MRI is appropriate for additional LUS diagnostics in patients with previous CS. The strong individual variability of LUS-anatomy and morphology might explain the difficulties in establishing uniform diagnostic standards after CS.

Anti-angiogenesis and Preeclampsia in 2016.

PURPOSE OF REVIEW: Preeclampsia remains one of the most important complications in pregnancy worldwide. With this review, we aim to give an overview on important research findings over the last years and their effects on current clinical management. RECENT FINDINGS: The association between preeclampsia and altered angiogenesis is nowadays widely accepted. Only during the last years, assessment of angiogenic factors such as the soluble fms-like tyrosine kinase-1-to-placental growth factor (sFlt-1/PlGF) ratio has become available to everyday clinical practice with commercially available automated measurements. With these, preeclampsia can be confirmed or ruled out in uncertainty of diagnosis, and a short-term prognosis can be given in patients with symptoms of preeclampsia. Pilot studies show that maternal serum levels of sFlt-1 can be reduced by therapeutic apheresis and that this might prolong pregnancy in case of very early severe preeclampsia. The automated measurement of the sFlt-1/PlGF ratio is starting to influence clinical management of preeclampsia. Apheresis might offer new treatment options, but still needs to be evaluated in randomized trials.