Association between prenatal glucocorticoid exposure and adolescent neurodevelopment: An observational follow-up study.

INTRODUCTION: Prenatal exposure to supraphysiological glucocorticoid (GC) levels may lead to long-lasting developmental changes in numerous biological systems. Our prior study identified an association between prenatal GC prophylaxis and reduced cognitive performance, electrocortical changes, and altered autonomic nervous system (ANS) activity in children aged 8-9 years. This follow-up study aimed to examine whether these findings persisted into adolescence. MATERIAL AND METHODS: Prospective observational follow-up study involving twenty-one 14- to 15-year-old adolescents born to mothers who received betamethasone for induction of fetal lung maturation in threatened preterm birth, but who were born with a normal weight appropriate for their gestational age (median 37+4 gestational weeks). Thirty-five children not exposed to betamethasone served as the reference group (median 37+6 gestational weeks). The primary endpoint was cognitive performance, measured by intelligence quotient (IQ). Key secondary endpoints included symptoms of attention-deficit/hyperactivity disorder (ADHD) and metabolic markers. Additionally, we determined electrocortical (electroencephalogram), hypothalamus-pituitary-adrenal axis (HPAA), and ANS activity in response to a standardized stress paradigm. RESULTS: No statistically significant group difference was observed in global IQ (adjusted mean: betamethasone 103.9 versus references 105.9, mean difference -2.0, 95% confidence interval [CI]: -7.12 to 3.12, p = 0.44). Similarly, ADHD symptoms, metabolic markers, the overall and stress-induced activity of the HPAA and the ANS did not differ significantly between groups. However, the betamethasone group exhibited reduced electrocortical activity in the frontal brain region (spectral edge frequency-adjusted means: 16.0 Hz versus 17.8 Hz, mean difference -1.83 Hz, 95% CI: -3.21 to -0.45, p = 0.01). CONCLUSIONS: In 14- to 15-year-old adolescents, prenatal GC exposure was not associated with differences in IQ scores or ANS activity compared to unexposed controls. However, decelerated electrocortical activity in the frontal region potentially reflects disturbances in the maturation of cortical and/or subcortical brain structures. The clinical significance of these changes remains unknown. Given the small sample size, selective participation/loss of follow-up and potential residual confounding, these findings should be interpreted cautiously. Further research is required to replicate these results in larger cohorts before drawing firm clinical conclusions.

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.

[Ethical Attitudes and Handling in Prenatal Conflict Situations - A Survey among Obstetricians and Prenatal Diagnosticians in Germany]. / Ethische Haltungen und Umgang in pränatalen Konfliktsituationen ­ eine Umfrage unter Geburtshelfern und Pränataldiagnostikern in Deutschland.

OBJECTIVE: Various studies have shown that belonging to a professional group has an influence on ethical attitudes. The aim of this study was to assess and compare the attitudes and approaches of obstetrical specialists and prenatal diagnosticians in prenatal conflict situations. METHODS: Explorative cross-sectional online survey among tertiary perinatal care centers and prenatal diagnosticians with DEGUM Level II/III in Germany. The questionnaire included questions on ethical attitudes in the perinatal context and a case presentation of a fetal hypoplastic left heart syndrome. RESULTS: The response rate was 57.1% (310/543). 55.5% of the respondents practiced both obstetrics and prenatal diagnostics, 24.5% exclusively prenatal diagnostics, and 14.2% purely obstetrics. 27% agreed with the statement "An uncertain prognosis justifies pregnancy termination". For complex fetal malformations joint interdisciplinary counseling was advocated by 98.3%. Addressing the option of postnatal palliative treatment in a case of a hypoplastic left heart syndrome was accepted by 84.3% across all professional groups, while mentioning fetocide was more frequently cited as an option by prenatal diagnosticians than by obstetricians (57.7% vs. 34.1%). CONCLUSION: Interdisciplinary prenatal parental counseling in complex fetal malformations is uniformly advocated by prenatal diagnosticians and obstetricians in Germany. However, different ethical attitudes appear among specialists groups with regard to the option of termination of pregnancy.

Vaginal and neonatal microbiota in pregnant women with preterm premature rupture of membranes and consecutive early onset neonatal sepsis.

BACKGROUND: Preterm premature rupture of membranes (PPROM), which is associated with vaginal dysbiosis, is responsible for up to one-third of all preterm births. Consecutive ascending colonization, infection, and inflammation may lead to relevant neonatal morbidity including early-onset neonatal sepsis (EONS). The present study aims to assess the vaginal microbial composition of PPROM patients and its development under standard antibiotic therapy and to evaluate the usefulness of the vaginal microbiota for the prediction of EONS. It moreover aims to decipher neonatal microbiota at birth as possible mirror of the in utero microbiota. METHODS: As part of the PEONS prospective multicenter cohort study, 78 women with PPROM and their 89 neonates were recruited. Maternal vaginal and neonatal pharyngeal, rectal, umbilical cord blood, and meconium microbiota were analyzed by 16S rRNA gene sequencing. Significant differences between the sample groups were evaluated using permutational multivariate analysis of variance and differently distributed taxa by the Mann-Whitney test. Potential biomarkers for the prediction of EONS were analyzed using the MetaboAnalyst platform. RESULTS: Vaginal microbiota at admission after PPROM were dominated by Lactobacillus spp. Standard antibiotic treatment triggers significant changes in microbial community (relative depletion of Lactobacillus spp. and relative enrichment of Ureaplasma parvum) accompanied by an increase in bacterial diversity, evenness and richness. The neonatal microbiota showed a heterogeneous microbial composition where meconium samples were characterized by specific taxa enriched in this niche. The vaginal microbiota at birth was shown to have the potential to predict EONS with Escherichia/Shigella and Facklamia as risk taxa and Anaerococcus obesiensis and Campylobacter ureolyticus as protective taxa. EONS cases could also be predicted at a reasonable rate from neonatal meconium communities with the protective taxa Bifidobacterium longum, Agathobacter rectale, and S. epidermidis as features. CONCLUSIONS: Vaginal and neonatal microbiota analysis by 16S rRNA gene sequencing after PPROM may form the basis of individualized risk assessment for consecutive EONS. Further studies on extended cohorts are necessary to evaluate how far this technique may in future close a diagnostic gap to optimize and personalize the clinical management of PPROM patients. TRIAL REGISTRATION: NCT03819192, ClinicalTrials.gov. Registered on January 28, 2019.

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.

German obstetrician's self-reported attitudes and handling in threatening preterm birth at the limits of viability.

OBJECTIVES: Antenatal treatment and information influences the course of pregnancy and parental decision-making in cases of threatened prematurity on the borderline of viability. Numerous studies have shown significant interprofessional differences in assessing ethical boundary decisions; hence, this study aimed to evaluate obstetricians attitudes, practices and antenatal parental counseling regarding threatened preterm birth in Germany. METHODS: An anonymous online questionnaire was administered to 543 obstetricians at tertiary perinatal centers and prenatal diagnostic centers in Germany. The survey contained questions on basic ethical issues assessed using the Likert scale and a case vignette regarding the practical procedures of an imminent extreme premature birth at 23 1/7 gestational weeks. RESULTS: In the case of unstoppable preterm birth, 15 % of clinicians said they would carry out a cesarean section; however, specialists from centers with a high number of very low birth weight infants would do so significantly more often. Among respondents, 29.8 % did not take any therapeutic measures without discussing the child's treatment options with their parents, 19.9 % refused to offer actionable advice to the parents, and 57 % said they would advise parents to seek intensive care treatment for the child with the option of changing treatment destination in the event of serious complications. Moreover, 84 % said they would provide information together with neonatologists. CONCLUSIONS: Joint counseling with neonatologists is widely accepted. The size of the perinatal center significantly influences the practical approach to threatened preterm births. Respect for parents' decision-making autonomy regarding the child's treatment options is central and influences therapy initiation.

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.

[Recommendations for SARS-CoV-2/COVID-19 during Pregnancy, Birth and Childbed - Update November 2021 (Short Version)]. / Empfehlungen zu SARS-CoV-2/COVID-19 in Schwangerschaft, Geburt und Wochenbett ­ Update November 2021 (Kurzfassung).

Since the onset of the SARS-CoV-2 pandemic, the German Society of Gynecology and Obstetrics and the Society for Peri-/Neonatal Medicine have published and repeatedly updated recommendations for the management of SARS-CoV-2 positive pregnancies and neonates. As a continuation of existing recommendations, the current update addresses key issues related to the prenatal, perinatal, and postnatal care of pregnant women, women who have recently given birth, women who are breastfeeding with SARS-CoV-2 and COVID-19, and their unborn or newborn infants, based on publications through September 2021. Recommendations and opinions were carefully derived from currently available scientific data and subsequently adopted by expert consensus. This guideline - here available in the short version - is intended to be an aid to clinical decision making. Interpretation and therapeutic responsibility remain with the supervising local medical team, whose decisions should be supported by these recommendations. Adjustments may be necessary due to the rapid dynamics of new evidence. The recommendations are supported by the endorsement of the professional societies: German Society for Perinatal Medicine (DGPM), German Society of Gynecology and Obstetrics (DGGG), German Society for Prenatal and Obstetric Medicine (DGPGM), German Society for Pediatric Infectiology (DGPI), Society for Neonatology and Pediatric Intensive Care Medicine (GNPI).

[Recommendations for SARS-CoV-2/COVID-19 during Pregnancy, Birth and Childbed - Update November 2021 (Long Version)]. / Empfehlungen zu SARS-CoV-2/COVID-19 in Schwangerschaft, Geburt und Wochenbett ­ Update November 2021 (Langfassung).

Since the onset of the SARS-CoV-2 pandemic, the German Society of Gynecology and Obstetrics and the Society for Peri-/Neonatal Medicine have published and repeatedly updated recommendations for the management of SARS-CoV-2 positive pregnancies and neonates. As a continuation of existing recommendations, the current update addresses key issues related to the prenatal, perinatal, and postnatal care of pregnant women, women who have given birth, women who have recently given birth, women who are breastfeeding with SARS-CoV-2 and COVID-19, and their unborn or newborn infants, based on publications through September 2021. Recommendations and opinions were carefully derived from currently available scientific data and subsequently adopted by expert consensus. This guideline - here available in the long version - is intended to be an aid to clinical decision making. Interpretation and therapeutic responsibility remain with the supervising local medical team, whose decisions should be supported by these recommendations. Adjustments may be necessary due to the rapid dynamics of new evidence. The recommendations are supported by the endorsement of the professional societies: German Society for Perinatal Medicine (DGPM), German Society of Gynecology and Obstetrics (DGGG), German Society for Prenatal and Obstetric Medicine (DGPGM), German Society for Pediatric Infectiology (DGPI), Society for Neonatology and Pediatric Intensive Care Medicine (GNPI).

[Cardiopulmonary resuscitation of pregnant patients in the rescue service]. / Kardiopulmonale Reanimation der schwangeren Patientin im Rettungsdienst: Standardisierter Ansatz für das notfallmedizinische Management.

Cardiopulmonary resuscitation of a pregnant patient is a rarity in prehospital emergency medicine and an extraordinary challenge for the emergency team. Besides modifications to emergency medical procedures due to physiological changes during pregnancy, specific reversible causes must be considered and psychosocial difficulties must be managed. This article aims to present a standard operating procedure for this special situation. In these circumstances the basics of crew resource management (CRM) are of special interest for the emergency team and are therefore mentioned in this article.

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.

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.

Influence of high glucose in the expression of miRNAs and IGF1R signaling pathway in human myometrial explants.

PURPOSE: Several roles are attributed to the myometrium including sperm and embryo transport, menstrual discharge, control of uterine blood flow, and labor. Although being a target of diabetes complications, the influence of high glucose on this compartment has been poorly investigated. Both miRNAs and IGF1R are associated with diabetic complications in different tissues. Herein, we examined the effects of high glucose on the expression of miRNAs and IGF1R signaling pathway in the human myometrium. METHODS: Human myometrial explants were cultivated for 48 h under either high or low glucose conditions. Thereafter, the conditioned medium was collected for biochemical analyses and the myometrial samples were processed for histological examination as well as miRNA and mRNA expression profiling by qPCR. RESULTS: Myometrial structure and morphology were well preserved after 48 h of cultivation in both high and low glucose conditions. Levels of lactate, creatinine, LDH and estrogen in the supernatant were similar between groups. An explorative screening by qPCR arrays revealed that 6 out of 754 investigated miRNAs were differentially expressed in the high glucose group. Data validation by single qPCR assays confirmed diminished expression of miR-215-5p and miR-296-5p, and also revealed reduced miR-497-3p levels. Accordingly, mRNA levels of IGF1R and its downstream mediators FOXO3 and PDCD4, which are potentially targeted by miR-497-3p, were elevated under high glucose conditions. In contrast, mRNA expression of IGF1, PTEN, and GLUT1 was unchanged. CONCLUSIONS: The human myometrium responds to short-term exposure (48 h) to high glucose concentrations by regulating the expression of miRNAs, IGF1R and its downstream targets.

[Guideline adherence and quality assurance in radiological diagnostics in cases of suspected child abuse in Germany]. / Leitlinientreue und Qualitätssicherung in der bildgebenden Diagnostik bei Verdacht auf Kindesmisshandlung in Deutschland.

BACKGROUND: Diagnostic imaging plays a key role in the evaluation of non-accidental consequences of injuries in childhood. Fractures are the second most common consequence of child abuse, after skin lesions such as abrasions or bleeding. With the evidence of radiological criteria, non-accidental fractures can be differentiated from accidental fractures. Special types of fractures such as the classic metaphyseal lesion can only be differentiated if the image quality is high. AIM: The goal of this prospective study was to assess adherence to guidelines and quality assurance of radiological diagnostics in the event of suspected abuse in Germany. For this purpose, the quantity and diagnostic quality in university and non-university hospitals as well as the existence of a pediatric radiology department were analyzed. MATERIALS AND METHODS: In all, 958 X­ray examinations of 114 suspected abuse cases (46 girls, 68 boys) were evaluated; 42 cases from university, 42 from maximum care and 30 from regular care clinics with a median age of 6 months (3 weeks-3 years of age) were assessed as DICOM data by 3 pediatric radiologists in a consensus procedure with regard to adherence to guidelines and various quality parameters. An accompanying questionnaire was used to compare the theoretical knowledge with the respective practical implementation. RESULTS: A mean of 8.4 X­rays (range 1-22) were made per case. In 12 of 114 assessed cases (10%) there was a complete skeletal status according to the S1 guideline. A babygram was performed in 13 cases (10.5%). Departments with focus on pediatric radiology produced significantly more X­rays per skeletal status than facilities without this specialization (p < 0.04). Significantly higher qualitative implementation was recorded in university hospitals (p < 0.001). Regardless of the type of institution, there was only marginal agreement between the questionnaire response and the available image material. CONCLUSION: In Germany, a guideline-compliant procedure in the event of suspected child abuse is largely lacking. It remains to be seen whether this will change in the future with the broader implementation of child protection groups and the S3+ child protection guideline adopted in 2019 (AWMF register 027-069). The establishment of reference centers for a second diagnosis and recommendations for imaging technology can also improve the quality of care over the long term.

Lethal Neonatal Respiratory Failure by Perinatal Transmission of Ureaplasma Parvum after Maternal PPROM.

A primiparous pregnant woman was admitted due to preterm premature rupture of membranes (PPROM) at 27+0 week of gestational age (WGA). Conventional vaginal microbiological analysis had no pathological finding. Management decisions based on national guidelines included antenatal corticoids, tocolytics and antibiotics. Unstoppable efforts of preterm labor in 28+0 WGA and supposed amniotic infection syndrome necessitated emergency cesarean section. The preterm infant underwent NICU therapy, developed an early-onset neonatal sepsis and therapy-refractory pulmonary insufficiency with consecutive right heart failure, resulting in death on the 36th day of life. Microbiota analyses by 16Sr DNA sequencing was performed from maternal vaginal swabs and from neonatal pharyngeal swabs. Maternal antibiotic treatment resulted in depletion of physiological vaginal colonization with Lactobacillus crispatus. Ureaplasma parvum became the dominant vaginal microorganism at delivery and was detected in high relative abundance in the neonatal specimen. Progressive radiological air-space changes and interstitial pathologies associated with Ureaplasma infection (bronchopulmonary dysplasia type III) were seen early at the 3rd and distinctly from 14th day of life. This clearly demonstrates the need of vaginal colonization diagnostics in PPROM patients and awareness of the consecutive risks in the preterm. Vaginal microbiome analysis may allow individualized and targeted maternal and fetal diagnostic, prophylactic and therapeutic strategies to identify, protect and treat the high-risk neonates after PPROM.

[Intrahepatic cholestasis of pregnancy]. / Schwangerschaftscholestase: In Zusammenarbeit mit der AG Geburtshilfe und Pränatalmedizin in der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe ­ Sektion Maternale Erkrankungen.

Intrahepatic cholestasis of pregnancy (ICP) is the most frequent pregnancy-specific liver disease. It is characterized by pruritus and an accompanying elevation of serum bile acid concentrations and/or alanine aminotransferase (ALT), which are the key parameters in the diagnosis. Despite good maternal prognosis, elevated bile acid concentration in maternal blood is an influencing factor to advers fetal outcome. The ICP is associated with increased rates of preterm birth, neonatal unit admission and stillbirth. This is the result of acute fetal asphyxia as opposed to a chronic uteroplacental insufficiency. Reliable monitoring or predictive tools (e.g. cardiotocography (CTG) or ultrasound) that help to prevent advers events are yet to be explored. Medicinal treatment with ursodeoxycholic acid (UDCA) does not demonstrably reduce adverse perinatal outcomes but does improve pruritus and liver function test results. Bile acid concentrations and gestational age should be used as indications to determine delivery. There is a high risk of recurrence in subsequent pregnancies.

Cervico-vaginal placental α-macroglobulin-1 combined with cervical length for the prediction of preterm birth in women with threatened preterm labor.

INTRODUCTION: Preterm birth is a major cause of neonatal morbidity and mortality. There is an urgent need to accurately predict imminent delivery to enable necessary interventions such as tocolytic, glucocorticoid, and magnesium sulfate administration. We aimed to evaluate placental α-macroglobulin-1 as a new diagnostic marker in the prediction of preterm birth. MATERIAL AND METHODS: We performed a prospective observational trial in women with intact membranes between 24+0 and 36+6 weeks of gestation. We included both women with and without threatened preterm labor symptoms. We evaluated the test performance of placental α-macroglobulin-1 measurements in cervicovaginal fluid regarding three different presentation-to-delivery intervals: ≤2, ≤7, ≤14 days. In addition, we calculated placental α-macroglobulin-1 performance in combination with other prognostic factors such as ultrasonographic cervical length measurements. RESULTS: We included 126 women in the study. We detected high specificity (97%-98%) and negative predictive value (89%-97%) for placental α-macroglobulin-1 at all time intervals. We assessed placental α-macroglobulin-1 in combination with cervical length measurements (≤15 mm) in the sub-group of women presenting with threatened preterm labor symptoms (n = 63) and detected high positive predictive values (100%) for 7- and 14-day presentation-to-delivery intervals. CONCLUSIONS: Our study provides evidence that placental α-macroglobulin-1 testing in cervicovaginal fluid, in combination with cervical length measurements, accurately predicts preterm birth in women with preterm labor symptoms. This novel test combination may be used clinically to triage women presenting with threatened preterm labor, avoiding overtreatment and unnecessary hospitalizations.

NUT midline carcinoma in a young pregnant female: a case report.

INTRODUCTION: The NUT midline carcinoma is a rare tumor mostly reported in the midline of upper aerodigestive tract and mediastinum. Children as well as adolescents are affected without a gender distribution. A standard treatment is not established. So far, there exists no reported case of a pregnant female suffering from NUT midline carcinoma with musculoskeletal manifestation. CASE PRESENTATION: A 34-year-old woman was referred to our outpatient clinic by the general practitioner during her 31st week of pregnancy suffering from shoulder pain and dyspnea. So far, dyspnea was interpreted as a typical pregnancy-related symptom. However, a chest X-ray showed a tumor mass in the right lung in close relation to the scapula. Further examinations found metastases in different areas of the body. No pregnancy-related complications were detected by obstetric examination. After an interdisciplinary perinatal case discussion, cesarean section was directly followed by an open biopsy of the right side scapula tumor lesion. A NUT midline carcinoma was diagnosed by immunohistochemistry. Due to disseminated tumor disease in multiple non-resectable locations, a palliative systemical chemotherapy was started by the oncological outpatient clinic. CONCLUSION: This report presents the case of the very rare NUT midline carcinoma under pregnancy which made interdisciplinary case discussions indispensable for therapy planning.