SPAM-sub partual analgesia with meptazinol: a prospective cohort study comparing intramuscular with intravenous administration.

PURPOSE: Safe and effective analgesia sub partu is one of the central issues in optimizing vaginal delivery birth experiences. Meptazinol is a common opiate approved for treating labor pain in the first stage of labor. According to the manufacturer, manual meptazinol can be applied intramuscularly or intravenously. The aim of this study was to compare the two application methods in terms of efficacy in pain relief, occurrence of side effects and treatment satisfaction. METHODS: 132 patients with singleton term pregnancies and intended vaginal delivery, receiving meptazinol during first stage of labor were included in this prospective cohort study from 05/2020 to 01/2021. We evaluated effectiveness in pain relief and treatment satisfaction using numeric rating scales (NRS) and documented the occurrence of adverse effects. Chi-square test or Fisher exact test were used to compare categorical data and Mann-Whitney U test to compare continuous data between the two treatment groups. Statistical analysis was done by SPSS 27.0. A p value < 0.05 was considered to indicate statistical significance (two tailed). RESULTS: Meptazinol decreased labor pain significantly from a NRS of 8 (IQR 8-10) to 6 (IQR 4.75-8) in both treatment groups with no difference in effectiveness between the groups. Frequency of effective pain reduction of a decrease of 2 or more on the NRS did not differ between groups (39.4% vs 54.5%, p = 0.116), as the occurrence of adverse effects. 12% of the newborns were admitted to NICU, the median NApH was 7.195. CONCLUSION: Meptazinol significantly reduces labor pain regardless of the method of application: intramuscular or intravenous. According to our data, no preferable route could be identified. The comparably poorer perinatal outcome in our study cohort hinders us to confirm that meptazinol is safe and can be recommended without restrictions.

Stillbirth in women with Type 1 Diabetes mellitus-still a current topic.

PURPOSE: Compared to the general stillbirth rate in Germany for term deliveries of 0.12% the risk in type 1 diabetes mellitus is reported to be up to ten times higher. The reasons for this excess risk of intrauterine demise are still not fully elucidated. Risk factors named in the literature include poor glycemic control before and during pregnancy and the occurrence of ketoacidosis. Additionally there might be a diabetes related type of placental dysfunction leading to organ failure in late pregnancy. Understanding the underlying causes is mandatory to develop strategies to reduce the incidences. The Purpose of this publication is to point out the difficulties in prediction of intrauterine death in pregnant type 1 diabetes patients and thus emphasizing the necessity of constant awareness to all caregivers. METHODS: We present a case series of four cases of stillbirth that occurred in patients with type 1 diabetes mellitus at our tertiary care obstetric unit during a five-year period. RESULTS: In all four presented cases the underlying cause of intrauterine demise was different and we could not find a common mechanism or risk profile. Furthermore, established monitoring tools did not become peculiar to raise awareness. We compared our cases to published data. Underlying causes of intrauterine death in type 1 diabetes are discussed in the light of the current literature. CONCLUSIONS: The main risk factors of stillbirth in diabetic pregnancies are high maternal blood glucose levels including pre-conceptional HbA1c and diabetic ketoacidosis. Late acute placental insufficiency are associated with intrauterine death in type 1 diabetes. Despite the elevated risk of near term intrauterine demise there are currently no guidelines on how to monitor pregnancies in type 1 diabetes for fetal distress during the third trimester. Established thresholds for fetal Doppler data indicating fetal distress in normal and growth restricted fetuses may not be applicable for overgrown fetuses. Future research on how to monitor the diabetic fetus needs to be initiated.

COVID-19, Pregnancy, and Diabetes Mellitus.

During the severe acute respiratory distress virus coronavirus type 2 (SARS-CoV-2) pandemic, many women were infected during their pregnancies. The SARS-CoV-2-induced coronavirus disease 19 (COVID-19) has an impact on maternal health and pregnancy outcomes; peripartum and perinatal morbidity and mortality are increased. Pregnancy is considered a risk factor for severe COVID-19 course. Additional risk factors during pregnancy are diabetes mellitus, gestational diabetes mellitus (GDM), and obesity. Systemic inflammation can lead to severe metabolic dysregulation with ketoacidosis. The endocrine pancreas is a target organ for SARS-CoV-2 and the fetal risk depends on inflammation of the placenta. Up to now there is no evidence that SARS-CoV-2 infection during pregnancy leads to permanent diabetes in mothers or their offspring via triggering autoimmunity or beta cell destruction. The frequently observed increased prevalence of GDM compared to the years before the pandemic is most likely due to changed lifestyle during lockdown. Furthermore, severe COVID-19 may be associated with the development of GDM due to worsening of glucose tolerance. Vaccination with a mRNA vaccine is safe and highly effective to prevent infection and to reduce hospitalization. Registries support offering evidence-based recommendations on vaccination for pregnant women. Even with the current omicron virus variant, there are increased risks for symptomatic and unvaccinated pregnant women.

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.

[SARS-CoV-2/COVID-19 and Hypertensive Pregnancy Disorders: Evaluation of the CRONOS National Registry]. / Hypertensive Schwangerschaftserkrankungen und SARS-CoV-2/COVID-19: Auswertung des nationalen CRONOS-Registers.

SARS-CoV-2 infection and COVID-19 disease are associated with an increased risk of hypertensive pregnancy disease in international registry studies. Preexisting hypertensive disorders are recognized as a risk factor of severe COVID-19 progression in pregnancy. The respective damage to the endothelium is discussed as a pathophysiological commonality of both diseases.Data of the national CRONOS registry (data status 05/2021; 1104 pregnant women with SARS-CoV-2 infection) were analyzed regarding the association of hypertensive pregnancy disease and maternal, pregnancy, neonatal, and COVID-19 disease outcomes. In the presence of hypertensive pregnancy disease, a severe combined outcome of pregnancy (17.3 vs. 4.3%, p=0.001), mother (25.0 vs. 9.4%, p=0.001), and newborn (28.8 vs. 9.1%, p<0.0005) occurred significantly more frequent. In contrast, the outcome of COVID-19 disease did not differ (3.8 vs. 7.5%, p=0.424). The co-occurrence of SARS-CoV-2 infection and hypertensive pregnancy disease should be acknowledged as risk factor during management decisions.

Gestational diabetes mellitus and COVID-19: results from the COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS).

BACKGROUND: Gestational diabetes mellitus is one of the most frequent pregnancy complications with a global prevalence of 13.4% in 2021. Pregnant women with COVID-19 and gestational diabetes mellitus are 3.3 times more likely to be admitted to an intensive care unit than women without gestational diabetes mellitus. Data on the association of gestational diabetes mellitus with maternal and neonatal pregnancy outcomes in pregnant women with SARS-CoV-2 infection are lacking. OBJECTIVE: This study aimed to investigate whether gestational diabetes mellitus is an independent risk factor for adverse maternal and fetal and neonatal outcomes in pregnant women with COVID-19. STUDY DESIGN: The COVID-19-Related Obstetric and Neonatal Outcome Study is a registry-based multicentric prospective observational study from Germany and Linz, Austria. Pregnant women with clinically confirmed COVID-19 were enrolled between April 3, 2020, and August 24, 2021, at any stage of pregnancy. Obstetricians and neonatologists of 115 hospitals actively provided data to the COVID-19-Related Obstetric and Neonatal Outcome Study. For collecting data, a cloud-based electronic data platform was developed. Women and neonates were observed until hospital discharge. Information on demographic characteristics, comorbidities, medical history, COVID-19-associated symptoms and treatments, pregnancy, and birth outcomes were entered by the local sites. Information on the periconceptional body mass index was collected. A primary combined maternal endpoint was defined as (1) admission to an intensive care unit (including maternal mortality), (2) viral pneumonia, and/or (3) oxygen supplementation. A primary combined fetal and neonatal endpoint was defined as (1) stillbirth at ≥24 0/7 weeks of gestation, (2) neonatal death ≤7 days after delivery, and/or (3) transfer to a neonatal intensive care unit. Multivariable logistic regression analysis was performed to evaluate the modulating effect of gestational diabetes mellitus on the defined endpoints. RESULTS: Of the 1490 women with COVID-19 (mean age, 31.0±5.2 years; 40.7% nulliparous), 140 (9.4%) were diagnosed with gestational diabetes mellitus; of these, 42.9% were treated with insulin. Overall, gestational diabetes mellitus was not associated with an adverse maternal outcome (odds ratio, 1.50; 95% confidence interval, 0.88-2.57). However, in women who were overweight or obese, gestational diabetes mellitus was independently associated with the primary maternal outcome (adjusted odds ratio, 2.69; 95% confidence interval, 1.43-5.07). Women who were overweight or obese with gestational diabetes mellitus requiring insulin treatment were found to have an increased risk of a severe course of COVID-19 (adjusted odds ratio, 3.05; 95% confidence interval, 1.38-6.73). Adverse maternal outcomes were more common when COVID-19 was diagnosed with or shortly after gestational diabetes mellitus diagnosis than COVID-19 diagnosis before gestational diabetes mellitus diagnosis (19.6% vs 5.6%; P<.05). Maternal gestational diabetes mellitus and maternal preconception body mass index of ≥25 kg/m2 increased the risk of adverse fetal and neonatal outcomes (adjusted odds ratio, 1.83; 95% confidence interval, 1.05-3.18). Furthermore, overweight and obesity (irrespective of gestational diabetes mellitus status) were influential factors for the maternal (adjusted odds ratio, 1.87; 95% confidence interval, 1.26-2.75) and neonatal (adjusted odds ratio, 1.81; 95% confidence interval, 1.32-2.48) primary endpoints compared with underweight or normal weight. CONCLUSION: Gestational diabetes mellitus, combined with periconceptional overweight or obesity, was independently associated with a severe maternal course of COVID-19, especially when the mother required insulin and COVID-19 was diagnosed with or after gestational diabetes mellitus diagnosis. These combined factors exhibited a moderate effect on neonatal outcomes. Women with gestational diabetes mellitus and a body mass index of ≥25 kg/m2 were a particularly vulnerable group in the case of COVID-19.

Association between antenatal glucocorticoid exposure and the activity of the stress system, cognition, and behavior in 8- to 9-year-old children: A prospective observational study.

INTRODUCTION: Glucocorticoid (GC) -induced fetal programming of the activity of the hypothalamus-pituitary-adrenal axis (HPAA) and its associated cognitive and behavioral consequences in later life have been well characterized in several animal species. However, information on humans is scarce. In this study, we examined HPAA activity markers and associated outcomes at 8 to 9 years of age among children prenatally exposed to GC for suspected preterm birth. Our hypothesis was that antenatal exposure to the betamethasone (BM) is associated with exacerbation of HPAA activity in childhood. MATERIAL AND METHODS: Prospective observational study in 31 children whose mothers received single (n = 19) or multiple (n = 12) courses of BM for threatened preterm birth but born with normal weight appropriate for the gestational age (median 37+6  weeks of gestation) compared with 38 non-exposed, age-matched children. Primary end point was the activity of the HPAA in response to the Trier Social Stress Test. Secondary end points were changes in autonomic nervous system (ANS) activity, cognitive performance (IQ), attention-deficit/hyperactivity disorder (ADHD) symptoms, and electrocortical activity (EEG). RESULTS: There was no statistically significant difference in HPAA activity markers between antenatal BM exposed and unexposed groups. ANS activity in BM-exposed children shifted towards a higher parasympathetic tone reflected by a higher overall high-frequency band power of heart rate variability. IQ scores were within normal limits for both groups; however, BM-exposed children had lower IQ scores than the unexposed group. BM-exposed group had marginally more ADHD core symptoms and increased electrocortical activity in the occipital brain region compared with controls. A monotonic dose-response relation between BM exposure and activity of the ANS and IQ was estimated in post-hoc analyses. CONCLUSIONS: Antenatal exposure to BM in the context of threatened preterm birth was not associated with changes in HPAA activity in childhood. However, BM exposure may be associated with changes in ANS activity. Antenatal GC prophylaxis is a valuable and often life-saving therapy, but its prescription may warrant a well-balanced risk-benefit assessment.

Predictors of a successful vaginal delivery in women with type 1 diabetes: a retrospective analysis of 20 years.

PURPOSE: To evaluate the independent factors associated with the success of a trial of vaginal birth (TVB) in women with type 1 diabetes. Despite all therapeutic efforts and technological innovations, rates of caesarean sections (CS) in pregnant women with type 1 diabetes remain unchanged above 60%. Our aim was to point out influencing factors to improve the quality of antepartum counseling. METHODS: We performed a retrospective cohort study of 195 pregnancies with type 1 diabetes treated between 2000 and 2019. After exclusions, 118 women with near-term singleton pregnancies intended vaginal birth (TVB). Group differences between CS and successful vaginal delivery were analyzed. Multivariate logistic regression was performed by including clinical and metabolic variables to determine the independent effects on a successful vaginal delivery. Subgroup analysis for nulliparous women. RESULTS: Of 118 women with TVB, 67 (56.8%) were delivered vaginally. History of previous vaginal delivery (OR 10.29; CI 2.39; 44.30), HbA1c changes during pregnancy (per % increase; OR 0.59; CI 0.36; 0.96) and gestational weight gain (per kg; OR 0.87; CI 0.80; 0.96) were independent predictors for a successful vaginal delivery. In nulliparous women, the duration of diabetes was independently and negatively associated with vaginal delivery. CONCLUSION: Provided data can help to improve antepartum counseling in type 1 diabetic patients. It seems that women with type 1 diabetes should avoid postponing pregnancy and childbirth.

Awareness of euglycaemic diabetic ketoacidosis during pregnancy prevents recurrence of devastating outcomes: a case report of two pregnancies in one patient.

BACKGROUND: Euglycaemic diabetic ketoacidosis (DKA) during pregnancy is a life-threatening obstetric emergency. It requires early identification and prompt action. Obstetricians' knowledge about symptoms, diagnostic pitfalls and management during pregnancy and delivery need to be improved. We report a case of a young diabetic woman developing severe euglycaemic DKA in two consecutive pregnancies; the first pregnancy resulted in the most deviating outcome (i.e., intrauterine death), while the second pregnancy resulted in the delivery of a healthy newborn. Thus, the novelty of the case presented here is the possibility to demonstrate how the management of DKA in pregnancy can dramatically change outcomes. CASE PRESENTATION: We report a case of a young diabetic woman in whom DKA was concealed by hyperemesis and oesophageal reflux. This woman presented to our delivery unit with severe euglycaemic DKA during her first pregnancy. While the mother's condition could be successfully stabilized, the foetus died shortly after admission. Two years later, the same woman presented with similar problems. Repeated episodes of mild euglycaemic DKA could be successfully managed with consequent interdisciplinary treatment and close observation, leading to a good pregnancy outcome, i.e., the birth of a healthy child. CONCLUSION: Awareness of euglycaemic DKA needs to be increased to reduce the risk of severe complications during pregnancies in diabetic women. This case report demonstrates that increased awareness of DKA with immediate recognition and a successful multidisciplinary approach are mandatory for an positive pregnancy outcomes.

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.

[COVID-19 and pregnancy]. / COVID-19 und Schwangerschaft: Fallserie mit der Komorbidität Diabetes aus der Registerstudie "Covid-19 Related Obstetric and Neonatal Outcome Study" (CRONOS).

From March 3 to October 13, 2020, 27 cases with diabetes comorbidity have been recorded in the CRONOS registry (Covid-19 Related Obstetric and Neonatal Outcome Study in Germany) among 262 registered women with SARS-CoV­2 infection during their pregnancy. Of those, 21 presented with gestational diabetes, 5 with type 2 diabetes and 1 with type 1 diabetes. About half of the women were asymptomatic and were diagnosed via general screening at hospital admission. The most common symptoms were nasal congestion, cough, tiredness, malaise and changes in smell and taste. The majority of pregnant women showed a mild to moderate course, three women were admitted to the intensive care unit and none required invasive ventilation. In the type 2 diabetes group, there were two cases with late fetal death (37 and 40 weeks of gestation) and one with a malformation, an association with diabetes being most likely. Pregnant women with diabetes mellitus represent a special subgroup; 1 in 10 women in this small cohort required intensive care monitoring due to COVID-19. In addition, this case series underscores the need for unrestricted access to pregnancy care, especially in times of pandemic, for optimal perinatal outcome.

Role of IL-36 Cytokines in the Regulation of Angiogenesis Potential of Trophoblast Cells.

IL-36 cytokines (the agonists IL-36α, IL-36ß, IL-36γ, and the antagonist IL-36Ra) are expressed in the mouse uterus and associated with maternal immune response during pregnancy. Here, we characterize the expression of IL-36 members in human primary trophoblast cells (PTC) and trophoblastic cell lines (HTR-8/SVneo and JEG-3) and upon treatment with bacterial and viral components. Effects of recombinant IL-36 on the migration capacity of trophoblastic cells, their ability to interact with endothelial cells and the induction of angiogenic factors and miRNAs (angiomiRNAs) were examined. Constitutive protein expression of IL-36 (α, ß, and γ) and their receptor (IL-36R) was found in all cell types. In PTC, transcripts for all IL-36 subtypes were found, whereas in trophoblastic cell lines only for IL36G and IL36RN. A synthetic analog of double-stranded RNA (poly I:C) and lipopolysaccharide (LPS) induced the expression of IL-36 members in a cell-specific and time-dependent manner. In HTR-8/SVneo cells, IL-36 cytokines increased cell migration and their capacity to interact with endothelial cells. VEGFA and PGF mRNA and protein, as well as the angiomiRNAs miR-146a-3p and miR-141-5p were upregulated as IL-36 response in PTC and HTR-8/SVneo cells. In conclusion, IL-36 cytokines are modulated by microbial components and regulate trophoblast migration and interaction with endothelial cells. Therefore, a fundamental role of these cytokines in the placentation process and in response to infections may be expected.

[Period Prevalence of SARS-CoV-2 in an Unselected Sample of Pregnant Women in Jena, Thuringia]. / Periodenprävalenz von SARS-CoV-2 in einer unselektierten Stichprobe schwangerer Frauen in Jena, Thüringen.

INTRODUCTION: Following an exponential increase in SARS-CoV-2 infections, the city of Jena, Thuringia, was the first in Germany to introduce mandatory mouth and nose coverings. An estimation of the SARS-CoV-2 period prevalence was achieved by screening an unselected cohort of pregnant women. Of interest was the number of unreported cases. METHODS: Upon admission to hospital, patients were screened for SARS-CoV-2 by a specific real-time PCR and antibodies determined by a specific SARS-CoV-2 IgG in serum by ELISA. The SARS-CoV-2 period prevalence was estimated using the Clopper-Pearson exact method, the group comparison with Fischer's exact test. RESULTS: From 6 April to 13 May 2020, 234 pregnant women were admitted to the Department of Obstetrics. A total of 225 (96.2%) SARS-CoV-2 PCRs were carried out and all remained negative. Specific IgG antibodies were detected in one (0.6%) of 180 (76.9%) antibody tests performed. The interval estimate of the period prevalence thus results in a 95% confidence interval between 0-1.7%. For 96 households with children, the period prevalence is 0-3.8%, which does not differ from the 0-4.8% for 76 households without children (p=1.00). DISCUSSION: This is the first report on the SARS-CoV-2 period prevalence of an unselected sample of pregnant women in Germany. Antibody testing showed no evidence of the feared high number of unreported asymptomatic SARS-CoV-2 infections. The seroconversion rate was below 1% (0.6%).

Pentaerythrityltetranitrate (PETN) improves utero- and feto-placental Doppler parameters in pregnancies with impaired utero-placental perfusion in mid-gestation - a secondary analysis of the PETN-pilot trial.

AIM: In pregnancies complicated by impaired utero-placental perfusion, pentaeritrithyltetranitrate (PETN) has been shown to reduce the risk of severe fetal growth restriction (FGR) and perinatal death by 39%. The effect is most likely related to the vasodilatative influence of PETN. To assess its impact on utero-placental and fetal perfusion, we analyzed the Doppler parameters measured during the PETN pilot-trial. METHODS: One hundred and eleven pregnancies presenting impaired utero-placental resistance at mid-gestation were included in the trial. Fifty-four women received PETN, while 57 received a placebo. Doppler velocimetry measurements were monitored biweekly. Statistical analysis was performed using a mixed linear model. RESULTS: Within the first week of treatment, the mean pulsatility index (PI) of the uterine artery (UtA) dropped more prominently in the PETN group [-0.20, 95% confidence interval (CI): -0.34 to -0.05, P=0.007). The adjusted relative risk (RR) for abnormal cerebro-placental ratio (CPR) was significantly reduced by PETN [RR 0.412 (95% CI: 0.181-0.941)]. Kaplan-Meier analysis demonstrates the postponement of absent end-diastolic flow (AED), absent or reverse end-diastolic flow (ARED), brain sparing and abnormal cerebroplacental ratio (CPR) in the PETN group. CONCLUSION: The demonstrated effect of PETN on utero-placental and feto-placental perfusion strengthens the evidence for a positive impact in pregnancies complicated by impaired placental perfusion and might explain the effect on neonatal outcome, as shown in the PETN-pilot trial.

[Pregnancy after Obesity and Metabolic Surgery - Risks and Complications]. / Schwangerschaft nach Adipositas- und metabolischer Chirurgie ­ spezielle Risiken und mögliche Komplikationen.

The increasing prevalence of morbid obesity in Germany is associated with an increasing number of metabolic surgical interventions. Short-term surgical and long-term metabolic complications - such as nutrient deficiencies - are the main risks of metabolic surgery and the resulting malabsorption. Obesity, especially morbid obesity, is associated with a high incidence of female infertility. One important cause of female infertility in obese women is the polycystic ovary syndrome, with 6 - 10%. Metabolic surgery significantly increases the fertility of obese women. The positive effect of obesity surgery on weight loss, remission of comorbidities, psychological outcome and fertility (in comparison with the effect of conservative treatment) has led to an increase in the number of metabolic operations. Nutrient deficiencies after restrictive, combined and malabsorptive procedures must be considered. Prophylaxis of these deficiencies during pregnancy after obesity surgery must be based on intensive interdisciplinary treatment. The aim of this overview is to characterise the metabolic complications and their prophylaxis, which are specific for the various bariatric procedures and which, subsequently, require temporary or permanent surveillance and supplementation.

Gestational diabetes mellitus: an evaluation of gynecologists' knowledge of guidelines and counseling behavior.

PURPOSE: Knowledge of risks, adequate pre- and post-partum care, and counseling is essential to reduce short- and long-term consequences for women with gestational diabetes mellitus (GDM) and their offspring. Our study explored the current GDM guideline knowledge and practiced patient counseling of private gynecologists in Germany. METHODS: A survey assessing the GDM guidelines and patient counseling was mailed to 775 practicing gynecologists. We evaluated the knowledge of maternal and offspring disease risks, counseling practice, and guideline awareness. Descriptive statistics were used to analyze the responses and Chi-Square or Fisher exact test to explore differences between groups. RESULTS: Of the 418 private gynecologists (54.1 % response rate) who responded, the majority was aware of obesity and GDM in the previous pregnancy as risk factors for GDM. To a lesser extent, risk factors like recurrent miscarriages and stillbirth were recalled. Eighty percent stated that GDM was associated with a higher risk for the development for hypertension and 96 % with type 2 diabetes in the mother. Respondents with knowledge of the current GDM guidelines were more often aware of the development of chronic diseases, counseled patients more frequently, and performed post-partum glucose screenings more regularly compared with private gynecologists with no knowledge of the guidelines. CONCLUSIONS: The majority of participants incorporated recent recommendations into their practice patterns for GDM. Providing private gynecologists with additional training may further improve care for women with GDM-affected pregnancies.

Erratum to: Impact of the nitric oxide-donor pentaerythrityl-tetranitrate on perinatal outcome in risk pregnancies: a prospective, randomized, double-blinded trial.

On page 1 "adjusted relative risk (RR)" should be changed to "adjusted odds ratio (OR)". On page 1, 3 and in the table head of table 2 "adjusted RR" should be changed to "adjusted OR". On page 3 "Mantel-Haenszel estimates of relative risk" should be changed to "Mantel-Haenszel estimates of odds ratios". In Table 2, caption b "Mantel-Haenszel estimate of relative risk" should be changed to "Mantel-Haenszel estimate of odds ratio".

Impact of the nitric oxide-donor pentaerythrityl-tetranitrate on perinatal outcome in risk pregnancies: a prospective, randomized, double-blinded trial.

Intrauterine growth restriction (IUGR) and preeclampsia (PE) are associated with impaired placentation. Patients who are at risk of developing both these disorders can be identified by abnormal uterine artery Doppler at mid-trimester pregnancy. Nitric oxide (NO)-donors like pentaerithrityl-tetranitrate (PETN) reduce the impedance in the uteroplacental vessels and possess protecting effects on the endothelium. We tested the effectiveness of the NO-donor PETN for secondary prevention of IUGR, PE, and preterm birth in pregnancies at risk. Some 111 women who presented with abnormal placental perfusion at 19-24 weeks of gestation (w.o.g.) were included into a prospective, randomized, placebo-controlled, double-blinded study. The primary endpoint was IUGR and/or perinatal death. Secondary endpoints were preterm birth, PE, and placental abruption. Pentaerithrityl-tetranitrate significantly decreased the risk for IUGR and/or perinatal death [adjusted odds ratio (OR) 0.410; 95% confidence interval, CI, 0.184-0.914] and for IUGR (adjusted OR 0.436; 95% CI 0.196-0.970). Preterm birth before 32 w.o.g. (adjusted OR 0.204; 95% CI 0.052-0.801) was reduced, but not the risk for PE. No placental abruption occurred in the PETN, but five occurred in the placebo group [corrected]. These results suggest that secondary prophylaxis of adverse pregnancy outcome might be feasible in pregnancies exhibiting abnormal placentation using PETN.

Gestational age at birth, birth weight, and gestational age when intrauterine brain sparing occurs determines the neonatal outcome in growth-restricted infants born before 32 weeks of gestation: a retrospective cohort analysis.

Background: Preterm birth and fetal growth restriction are the main determinants of perinatal mortality. In the absence of therapeutic interventions, management is restricted to the observation of fetal growth and fetoplacental perfusion to determine the timing of delivery. Fetal circulatory redistribution, known as "brain sparing," represents a sign of fetal hypoxia and has been implemented in algorithms for when to deliver. In the absence of any other option, the nitric oxide donor pentaerythrityl tetranitrate (PETN), which has been shown to improve fetoplacental flow and reduce preterm birth in high-risk patients, is offered to patients as a personal therapy attempt. The aim of this study was to evaluate determinants related to pregnancy, including PETN intake during pregnancy, on immediate neonatal outcomes in a cohort of growth-restricted infants born before 32 completed weeks of gestation. Methods: We performed a retrospective cohort study of 98 infants born with a birth weight below the 10th percentile before 32 completed weeks of gestation at our tertiary care center between 2010 and 2019. PETN was offered to all mothers with a history of severe adverse pregnancy outcomes who were at high risk of developing fetal growth restriction as an individual therapy attempt. Results: The mean gestational age at birth was 188.5 days, and the mean birth weight was 549 g, corresponding to a median percentile of three. In 73 (79.3%) cases, brain sparing occurred during pregnancy. A total of 22 (22.4%) neonates were stillborn, 20 died postnatally, and 37.3% developed a severe complication. Multivariable analysis revealed birth weight percentile, gestational age at birth, and gestational age when brain sparing first occurred to be robust predictors of mortality or severe neonatal morbidity. In 39 neonates of mothers taking PETN, this impact of brain sparing was not observed. Conclusion: Our study is the first to demonstrate a significant association between the early occurrence of brain-sparing and severe neonatal outcomes in a cohort of very early preterm, growth-restricted newborns. The data suggest that PETN intake may ameliorate the effect of brain sparing in the affected neonates.