Prognostic Value of Cerebroplacental Ratio in Appropriate-for-Gestational-Age Fetuses Before Induction of Labor in Late-Term Pregnancies.

PURPOSE: To evaluate the relationship between cerebroplacental ratio (CPR) and the need for operative delivery due to intrapartum fetal compromise (IFC) and adverse perinatal outcome (APO) in appropriate-for-gestational-age (AGA) late-term pregnancies undergoing induction of labor. The predictive performance of CPR was also assessed. MATERIALS AND METHODS: Retrospective study including singleton AGA pregnancies that underwent elective induction of labor between 41 + 0 and 41 + 6 weeks and were delivered before 42 + 0 weeks. IFC was defined as persistent pathological CTG or pathological CTG and fetal scalp pH < 7.20. Operative delivery included instrumental vaginal delivery (IVD) and cesarean section (CS). APO was defined as a composite of umbilical artery pH < 7.20, Apgar score < 7 at 5 minutes, and admission to the neonatal intensive care unit for > 24 hours. RESULTS: The study included 314 women with 32 (10 %) IVDs and 49 (16 %) CSs due to IFC and 85 (27 %) APO cases. Fetuses with CPR < 10th percentile showed a significantly higher rate of operative delivery for IFC (40 % (21/52) vs. 23 % (60/262); p = 0.008) yet not a significantly higher rate of APO (31 % (16/52) vs. 26 % (69/262); p = 0.511). The predictive values of CPR for operative delivery due to IFC and APO showed sensitivities of 26 % and 19 %, specificities of 87 % and 84 %, positive LRs of 2.0 and 1.2, and negative LRs of 0.85 and 0.96, respectively. CONCLUSION: Low CPR in AGA late-term pregnancies undergoing elective induction of labor was associated with a higher risk of operative delivery for IFC without increasing the APO rate. However, the predictive value of CPR was poor.

Perinatal Outcome and its Prediction Using Longitudinal Feto-Maternal Doppler Follow-Up in Late Onset Small for Gestational Age Fetuses - A Prospective Cohort Study.

PURPOSE: To describe the perinatal outcome of a prospective cohort of late-onset small-for-gestational-age (SGA) fetuses and to test adverse perinatal outcome (APO) prediction using Doppler measurements. METHODS: Singleton pregnancies from 32 weeks with suspicion of SGA (followed-up each 2 weeks) and randomly selected healthy controls at a university hospital were included. The whole SGA group was divided into the FGR subgroup or SGA percentile 3-10 subgroup. The following Doppler measurements were evaluated prospectively: umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, cerebro-placental ratio (CPR), and mean uterine artery (mUtA) PI. APO was defined as arterial cord blood pH ≤ 7.15 and/or 5-minute Apgar ≤ 7 and/or emergency operative delivery and/or admission to the neonatal unit. Induction of labor was indicated according to a stage-based protocol. RESULTS: A total of 149 SGA and 143 control fetuses were included. The number of operative deliveries was similar between both groups (control: 29 %, SGA: 28 %), especially the cesarean delivery rate after the onset of labor (11 % vs. 10 %). Most SGA cases ended up in induction of labor (61 % vs. 31 %, p < 0.001). The areas under the curve (AUC) for APO prediction were similar using the last UA PI, MCA PI, CPR, and mUtA PI and barely reached 0.60. The AUC was best for the FGR subgroup, using the minimal CPR or maximum mUtA PI z-score of all longitudinal measurements (AUC = 0.63). CONCLUSION: SGA fetuses do not have a higher rate of operative delivery if managed according to a risk stratification protocol. Prediction of APO is best for SGA and FGR using the "worst" CPR or mUtA PI but it remains moderate.

Platelet mitochondrial membrane depolarization reflects disease severity in patients with preeclampsia.

BACKGROUND: Thrombocytopenia is a feared complication of preeclampsia (PE) that can additionally complicate the disease course and that carries a poor prognosis. The disease mechanisms of PE on a platelet level are poorly understood and only few platelet-based markers have been investigated. In sepsis, platelet mitochondrial membrane depolarization, a sensitive and early indicator of mitochondrial dysfunction and platelet cell death, correlates with disease severity and outcome as shown in previous studies. The aim of this study was to investigate platelet mitochondrial membrane potential (Mmp-Index) by flow-cytometry in patients with preeclampsia compared to controls and to assess its value in correlation with disease severity of PE and during follow-up after delivery. METHODS: In this prospective translational case-control study, platelet Mmp-Index was measured in PE (n = 16) by flow cytometry in living platelets in simultaneous comparison to healthy pregnant (n = 32) and non-pregnant controls (n = 16) and was individually reassessed after delivery to investigate recovery of platelet mitochondrial function. Subgroup analysis of patients with severe and non-severe PE was performed. Six patients with isolated gestational hypertension were also included for comparative analysis. RESULTS: Platelet Mmp-Index in patients with symptomatic preeclampsia (Mmp-Index non-severe PE 0.72 ([0.591; 0.861]; p = 0.002) was significantly reduced compared to healthy pregnant controls (Mmp-Index 0.97 [0.795; 1.117]) and even more pronounced in patients with severe PE (n = 6) (Mmp-Index severe PE 0.542 [0.361; 0.623]; p = 0.03). In the severe PE group, complementary measurements of platelet Annexin V- and CD62 (P-Selectin) surface expression showed apoptosis of platelet populations in the majority of patients. Platelet Mmp normalized after delivery within few days. Patients with isolated gestational hypertension showed normal Mmp-Index values. CONCLUSIONS: This study shows for the first time that platelet Mmp-Index is a quantifiable, easy-to-measure intracellular marker of platelet mitochondrial function in vital cells that reflects disease severity of preeclampsia. For future investigations, platelet Mmp may serve as a prognostic marker that may aid clinical risk stratification and adds novel information on potential mechanisms for thrombocytopenia in preeclampsia.

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.

Myocardial deformation analysis in late-onset small-for-gestational-age and growth-restricted fetuses using two-dimensional speckle tracking echocardiography: a prospective cohort study.

OBJECTIVES: An association between fetal growth restriction (FGR) and increased predisposition to cardiovascular disease (CVD) is suggested. The aim of this study was to evaluate subclinical signs of fetal cardiac remodeling in late-onset small-for-gestational-age (SGA) and growth-restricted fetuses using two-dimensional speckle tracking echocardiography (2D-STE). METHODS: This is a prospective cohort study, including 117 late-onset (≥32 weeks) SGA (birthweight≤10th centile) fetuses and 102 gestational age matched controls. A subgroup analysis was performed: FGR was defined based on either BW (0.05). Regarding global and segmental LPSS and LSR values of LV/RV, subgroup analysis revealed no significant difference between the FGR (n=81), SGA centile 3-10 (n=36) and control group. CONCLUSIONS: A mild degree of placental dysfunction seems not to influence myocardial deformation properties measured by 2D-STE.

Experiences with alternative online lectures in medical education in obstetrics and gynecology during the COVID-19 pandemic-possible efficient and student-orientated models for the future?

PURPOSE: The onset of the COVID-19 pandemic posed an eminent challenge for medical teachers worldwide. Face-to-face lectures and seminars were no longer possible, and alternatives had to be found. E-learning concepts quickly emerged as the only practicable solutions and also offered the opportunity to evaluate whether traditional face-to-face lectures could be translated into an online format, independent of the COVID-19 pandemic. METHODS: We offered an e-learning program consisting of lecture notes, screencasts with audio narration, and online webinars that covered topics normally taught in traditional lectures and seminars. To evaluate the learning behavior and quality of our e-learning program, we drafted a questionnaire that students completed at the end of the 2020 summer semester that had been designed to enable a comparative analysis of the different e-learning modules. RESULTS: Voluntary participation in the online courses was high. Survey analysis revealed high satisfaction with and a distinctive preference for the format, even under regular, COVID-19-independent conditions. In general, a positive appraisal of e-learning-especially as a substitute for regular lectures-was found. Students also reported higher studying efficiency. Exam results were equal to those of previous semesters. CONCLUSION: Both acceptance of and satisfaction with our e-learning modules were high, and students displayed increased demand for this kind of e-learning format. We, therefore, conclude that e-learning offerings could serve as reasonable, efficient, student-orientated substitutes for certain medical courses, especially lectures. These curricular adaptations would correlate with the high digitalization seen in students' everyday lives. This correlation may also hold true independent of the ongoing COVID-19 pandemic.

Does gestational age at term play a role in the association between cerebroplacental ratio and operative delivery for intrapartum fetal compromise?

INTRODUCTION: To assess the impact of gestational age at term on the association between cerebroplacental ratio (CPR) and operative delivery for intrapartum fetal compromise (IFC) and prognostic performance of CPR to predict operative delivery for IFC. MATERIAL AND METHODS: This was a retrospective cohort study including 2052 singleton pregnancies delivered between 37+0 and 41+6  weeks of gestation in a single tertiary referral center over an 8-year period. CPR was measured within 1 week of delivery. IFC was defined as the presence of persistent pathological cardiotocography pattern or the combination of pathological cardiotocography pattern and fetal scalp pH < 7.20. Operative delivery included instrumental vaginal delivery and cesarean section. Pregnancies were grouped according to birthweight (small for gestational age [SGA, birthweight <10th centile] and appropriate for gestational age [AGA, birthweight 10th-90th centile]) and gestational age by week at delivery. Rates of operative delivery were compared between the subgroups. Prognostic value of CPR was assessed using receiver operating characteristic curve. RESULTS: Of the study cohort, 308 (15%) had a CPR <10th centile, 374 (18%) operative delivery for IFC, and 298 (15%) were SGA at birth. Overall, the rates of operative delivery for IFC were higher in the low CPR group both in SGA (35% vs. 22%; p = 0.023) and in AGA (23% vs. 16%; p = 0.007). According to gestational age by week at delivery, fetuses with low CPR showed higher rates of operative delivery for IFC with advancing gestational age, mainly in pregnancies delivered at 40 weeks (54% vs. 23%; p = 0.004) and at 41 weeks (60% vs. 19%; p = 0.010) for SGA and at 41 weeks (39% vs. 20%; p = 0.001) for AGA. The predictive value of CPR remained stable throughout term and was poor both in SGA and in AGA. CONCLUSIONS: Both SGA and AGA fetuses with low CPR showed higher rates of operative delivery for IFC at term with advancing gestational age. Prognostic value of CPR throughout term was poor.

Intrapartum PRSA: a new method to predict fetal acidosis?-a case-control study.

PURPOSE: Phase-rectified signal averaging method (PRSA) represents an analysis method which applied on fetal cardiotocography (CTG) allows the quantification of the speed of fetal heart rate changes. By calculating the average deceleration capacity (ADC) an assessment of the fetal autonomic nervous system (ANS) is possible. The objective of this study was to test its ability to predict perinatal acidosis. METHODS: A case-control study was performed at a University Hospital in Munich. All intrapartum CTG heart rate tracings saved during a 7-year period were considered for analysis. All neonates born with an umbilical arterial blood pH ≤ 7.10 were considered as cases. Controls were defined as healthy fetuses born with a pH ≥ 7.25. The main matching criteria were gestational age at delivery, parity, birth mode, and birth weight percentile. Exclusion criteria were a planned caesarean section, fetal malformations, and multiple pregnancies. ADC and STV were then calculated during the last 60, the last 45, and the last 30 min intervals prior to delivery. RESULTS: Of all stored birth CTG recordings, 227 cases met the inclusion criteria and were studied. ADC was significantly higher in fetuses born with acidemia (4.85 bpm ± 3.0) compared to controls (3.36 bpm ± 2.2). The area under ROC curve was 0.659 (95% CI 0.608-0.710) for ADC and 0.566 (0.512-0.620) for STV (p = 0.013). CONCLUSIONS: This study confirms that the assessment of ADC using PRSA represents a good additional tool for the prediction of acute fetal acidosis during delivery.

Role of sFlt-1/PlGF ratio and feto-maternal Doppler for the prediction of adverse perinatal outcome in late-onset pre-eclampsia.

PURPOSE: The sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio and uterine artery Doppler have shown to be helpful in the diagnosis of pre-eclampsia (PE). The predictive value of the cerebroplacental ratio (CPR) regarding adverse perinatal outcome (APO) in low-risk pregnancies is intensively discussed. We evaluated the extent to which sFlt-1/PlGF ratio and feto-maternal Doppler may be useful in predicting APO in singleton pregnancies complicated by late-onset PE and/or HELLP syndrome. METHODS: This is a retrospective study from 2010 to 2018 consisting of singleton pregnancies with confirmed diagnosis of late-onset (lo ≥ 34 weeks) PE/HELLP syndrome in which sFlt-1/PlGF ratio and feto-maternal Doppler (mUtA-PI: mean uterine artery pulsatility index and CPR) were determined. The ability of sFlt-1/PlGF ratio, mUtA-PI, CPR and their combination to predict APO or SGA was evaluated using receiver operating characteristic (ROC) curves. RESULTS: 67 patients were included in the final analysis. Of these, sFlt-1/PlGF was > 110 (defining angiogenic lo PE) in 40.3% (27/67), mUtA-PI was above the 95th centile in 34.3% (23/67) patients and CPR was lower than the 5th centile in 10.4% (7/67). Abnormal sFlt-1/PlGF and mUtA-PI as well as CPR were associated with a lower birth weight (BW). Late-preterm birth (< 37 weeks) as well as postnatal diagnosis of small for gestational age (SGA: BW < 3rd centile) was significantly more often in angiogenic lo PE cases. Neither sFlt-1/PIGF nor CPR or mUtA-PI were APO predictors. Only for sFlt-1/PlGF, ROC analysis revealed a significant predictive value for postnatal SGA (AUC = 0.856, p = 0.001, 95% CI 0.75-0.97). There was no statistical added value of combined SGA predictors as compared to sFlt-1/PlGF alone. CONCLUSIONS: In patients with lo PE, adding sFlt-1/PlGF ratio to routine antepartum fetal surveillance may be useful to identify cases of postnatal SGA. However, further prospective studies are warranted to define the role of feto-maternal Doppler and sFlt-1/PlGF ratio as outcome predictors.

[Systemic drug treatment during pregnancy]. / Medikamentöse Systemtherapie in der Schwangerschaft.

In clinical routine, treatment of pregnant women is a recurring challenge. The frequent opacity of current studies, lack of reliable sources of information and the general insecurity of pregnant women towards systemic drug treatment leads to difficult clinical decision making. Potent therapies with sufficient clinical experience in terms of safety of application are available for most diseases seen in pregnancy. After careful evaluation of potential benefits and risks of a therapy, not only the optimal choice of a medical treatment, but also adequate control of clinical symptoms and interdisciplinary care are crucial for a safe pregnancy.

Performance of computerized cardiotocography-based short-term variation in late-onset small-for-gestational-age fetuses and reference ranges for the late third trimester.

PURPOSE: Fetal Doppler changes are well characterized in early-onset small-for-gestational-age (SGA) and fetal growth restriction (FGR) but less well characterized where the condition is late-onset. The aim of the study was to evaluate the role of computerized CTG (cCTG)-based short-term variation (STV) in late-onset SGA and FGR as an additional monitoring modality and to establish STV reference ranges in late third trimester healthy pregnancies. METHODS: Of 86 late-onset SGA fetuses diagnosed after 32 weeks, 66 were diagnosed with FGR. 138 healthy pregnancies acted as controls. All underwent umbilical artery pulsatility index (PI), middle cerebral artery PI, cerebroplacental ratio and mean uterine artery PI. cCTG recordings were analyzed by Sonicaid FetalCare software for STV calculation as described by Dawes/Redman. RESULTS: Median interval between inclusion and delivery was 13 (interquantile range = 4-30) days in the FGR group, 22 (12-37) days in the SGA group and 25 (10-40) days in the control group. STV was not different between controls (11.2 ms, 9.7-13.1), late-onset SGA (11.2 ms, 8.1-12.6) and FGR (10.5 ms, 8.5-12.4) fetuses. A greater proportion of late-onset SGA fetuses had STV < 5th percentile (7/86) compared to controls (4/138) (8.1% vs. 2.9%, p = 0.077). In the control group a significant positive correlation was seen between STV, and 1-min (ρ = 0.195, p = 0.026), 5-min (ρ = 0.247, p = 0.004) and 10-min (ρ = 0.211, p = 0.014) Apgar values. CONCLUSIONS: We report no significant difference in STV median values between controls, SGA and FGR pregnancies. However, more SGA fetuses had a low STV compared to controls. Prospective longitudinal studies are needed to investigate if low STV is a useful surveillance method for late-onset FGR.

Application of the INTERGROWTH-21st chart compared to customized growth charts in fetuses with left heart obstruction: late trimester biometry, cerebroplacental hemodynamics and perinatal outcome.

PURPOSE: Birth weight (BW) is crucial for surgical outcome in children with left heart obstruction (LHO). Head circumference (HC) is believed to correlate with the neurocognitive outcome in LHO. Our aim was to investigate the application of international standardized growth charts from the INTERGROWTH-21st project in comparison to customized growth charts in fetal LHO. METHODS: This is a retrospective cohort study consisting of 60 singleton pregnancies complicated by fetal LHO. For the z score calculation of estimated fetal weight (EFW) and biometric parameters, the INTERGROWTH-21st calculator was used as well as algorithms of customized growth charts. Antenatal measurements were compared to newborn biometry and the association with fetal Doppler results (MCA PI: middle cerebral artery pulsatility index and CPR: cerebroplacental ratio) was examined. Furthermore, the ability of each antenatal chart to predict adverse perinatal outcome was evaluated. RESULTS: At a mean gestational age of 37 weeks, all assessment charts showed significantly smaller mean values for antenatal head circumference (HC) z scores. Highest detection rate for restricted HC growth antenatally was achieved with Hadlock charts. MCA PI and CPR were not associated with neonatal HC. A significant association was observed between EFW and 1-year survival, independent of the considered growth chart. CONCLUSIONS: Growth chart independently, antenatal HC did tend to be smaller in LHO fetuses. A significant association was observed between EFW and 1-year survival rate. Prospective investigations in CHD fetuses should be carried out with internationally standardized growth charts to better examine their prognostic value in this high-risk population.

[Maternal Tumor Disease as a Reason for Repeated Test Failure in Cell-Free DNA Screening]. / Mütterliches Malignom in der Schwangerschaft als Ursache eines wiederholten Testversagens im nicht-invasiven Pränataltest.

Noninvasive prenatal testing (NIPT) is a screening test for fetal chromosome disorders. Recent studies show an incidental detection of maternal malignancies in NIPT diagnostics, where the simultaneous presence of multiple aneuploidies is described as an NIPT "anomaly". In this case, the diagnosis of a maternal tumor disease was made due to a repeat NIPT failure (no call).

Esophageal achalasia and pregnancy: own observations in 43 patients and a review of the literature.

INTRODUCTION: Little is known concerning the interaction of achalasia and pregnancy and about an optimal time and type for treatment. Achalatic women of our collective of patients with at least one pregnancy in their history resulting in confinement or miscarriage were invited for a structured interview. MATERIALS AND METHODS: 43 of 109 female patients were included. Questionnaire contained questions on symptoms, type of symptoms, whether patients could link a specific event with outbreak of disease. Date of primary diagnosis and individual therapies were double checked against our documentation as well as duration of complaints and kind of therapy. Patients were asked about their obstetric history, whether and how symptoms had changed, and during which pregnancy week symptoms have occurred. Temporal correlation of the diagnosis of achalasia and pregnancy was investigated. RESULTS: There was no relationship between pregnancy and onset of achalasia. Risk of subfertility, undernourishment, premature birth, or miscarriage does not seem to be increased in achalasia. Health condition often worsened significantly during pregnancy, mainly in the first trimester and particularly in the untreated patients. CONCLUSIONS: It is advisable to clarify the diagnosis if symptoms suspicious of an achalasia are present before a planned pregnancy. In case of manifest achalasia, surgical treatment should be performed before pregnancy and the improvement in the state of health should be anticipated, as, otherwise, a considerable deterioration of the symptoms during pregnancy may occur. Scientific impact of our observations is very limited and prospective clinical trials are required.

sFlt-1/PlGF ratio for the prediction of the time of delivery.

PURPOSE: The soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio has been shown to be a useful parameter for the diagnosis and prediction of preeclampsia (PE). An increased sFlt-1/PlGF ratio can be closely linked to the need to deliver. The aim of the study was to examine the mean time until delivery (MTUD) in pregnant women with a strongly increased sFlt-1/PlGF ratio. METHODS: From 2010 to 2018, the sFlt-1/PlGF ratio was determined in 995 singleton pregnancies with diagnosis or suspicion of PE/HELLP syndrome and/or intrauterine growth restriction (IUGR). MTUD of patients with a value above 655 in < 34 weeks of gestation (group 1: n = 13) and above 201 in ≥ 34 weeks of gestation (group 2: n = 15) was calculated. Patients with a value > 85 but < 655 in < 34 weeks of gestation (group 3: n = 70) and a value > 110 but < 201 (group 4: n = 44) in ≥ 34 weeks of gestation acted as controls. RESULTS: 28 pregnant women with severely elevated sFlt-1/PlGF ratio and 114 controls were included. In group 1, MTUD was longer compared to group 2 without reaching statistical significance (96.7 h ± 132.2 vs. 47.7 h ± 44, p = 0.222). In pregnancies < 34 weeks of gestation (early onset), MTUD was significantly longer in group 3 compared to group 1 (361 h ± 317.3 vs. 96.7 h ± 132.2, p < 0.001). In pregnancies ≥ 34 weeks of gestation (late onset), MTUD was significantly longer in group 4 compared to group 2 (123.6 h ± 139.2 vs. 47.7 h ± 44, p = 0.002). CONCLUSIONS: The sFlt-1/PlGF ratio is suitable for decision-making regarding close monitoring of high-risk patients and need for lung maturation. However, for planning of delivery itself further prospective interventional studies are required to define its role as outcome predictor.

Frequency of Miscarriage/Stillbirth and Terminations of Pregnancy Among Women With Congenital Heart Disease in Germany, Hungary and Japan.

BACKGROUND: The 2011 guidelines of the European Society of Cardiology (ESC) on the management of cardiovascular diseases during pregnancy define the maternal predictors for neonatal complications. The aim of this study was to determine whether these are associated with an increased number of miscarriages/stillbirths and terminations of pregnancy (TOPs) also in patients with congenital heart defects (CHD). METHODS AND RESULTS: The 634 women from Germany, Hungary and Japan were surveyed concerning the issues of sexuality and reproductive health, as well as their general life situation and medical care. 25% of the recorded pregnancies in women with CHD resulted in miscarriage, stillbirth or TOP. Affecting 16.8% of all recorded pregnancies, miscarriages or stillbirths occurred more frequently than in the general population and more than previously recorded for patients with CHD. TOP occurred in 8% of the surveyed pregnancies. Underlying maternal predictors for neonatal events had an influence on the number of TOP; among those with underlying predictors, TOP was recorded 3-fold more than in those without such predictors (15.6% vs. 5.5%). Remarkably, a significant deficit regarding the level of information on potential pregnancy-associated risks was observed in all 3 participating countries. CONCLUSIONS: Pregnant women with CHD should always be treated and counseled individually by cardiologists, gynecologists, obstetricians and anesthetists with appropriate expert knowledge. (Circ J 2016; 80: 1846-1851).

Management of Rheumatic Diseases During Pregnancy and Breastfeeding: Position Paper of the Working Group for Obstetrics and Prenatal Medicine in the German Society for Gynecology and Obstetrics e. V. (AGG - Section Maternal Diseases in Pregnancy).

Purpose These recommendations issued by the AGG (Section Maternal Diseases in Pregnancy) were developed as a rapid orientation on maternal rheumatic diseases for counselling and disease management in pregnancy and breastfeeding. Methods The standard literature, consensus and position papers, guidelines and recommendations by other specialist associations were evaluated by a task force of the Section and summarized in these recommendations following a joint consensus process. Recommendations This paper provides an orientating overview of the physiology, pathophysiology and definitions of rheumatic diseases which is relevant for gynecologists and obstetricians. The recommendations focus on the maternal, fetal and neonatal diagnostic workup in cases with underlying maternal rheumatic disease.

The Outcome after Laser Therapy of Monochorionic Twin Pregnancies Complicated by Twin-Twin Transfusion Syndrome with Coexistent Selective Fetal Growth Restriction.

Background: Most previous studies evaluated outcomes of twin-twin transfusion syndrome (TTTS) without considering the coexistence of selective fetal growth restriction (sFGR). The objectives of this study were to compare twin survival and pregnancy complications after laser therapy of TTTS with and without sFGR. Methods: For this purpose, a retrospective cohort study including 98 monochorionic diamniotic twins and three dichorionic triamniotic triplets treated in a single tertiary center was conducted. Results: Overall, 46 twins had selective fetal growth restriction (26 type I, 13 type II, 7 type III). At birth, donor survival (61% vs. 91%), double survival (57% vs. 82%), and overall survival (75% vs. 88%) were significantly lower in the group with coexistent sFGR. Recipient survival (89% vs. 86%), miscarriage (7% vs. 2%), PPROM < 32 weeks (48% vs. 29%), and preterm delivery < 32 weeks (52% vs. 45%) were not significantly higher in the group with coexistent sFGR. Donor twins with sFGR type I (69% vs. 91%) and types II-III (50% vs. 91%) showed significantly lower survival than those without sFGR. Multivariate regression analysis identified sFGR and its subtypes as independent predictors of donor demise. Conclusions: the coexistence of sFGR in TTTS pregnancies was associated with poor donor outcomes and is probably the most important predictor of donor survival.

New Markers for Placental Dysfunction at Term - Potential for More.

The remaining placental reserve capacity at term plays a decisive role in the perinatal morbidity of mother and child. Considering advances made in the field of fetal monitoring, the routine examination methods currently used at term or late term may be insufficient to detect subclinical placental dysfunction (PD). The aim of this study is to offer an up-to-date, narrative review of the literature in the context of detecting PD at term using complementary ultrasound markers and biomarkers. Parameters of fetomaternal Doppler ultrasound and fetal cardiac function, as well as (anti-)angiogenic factors in maternal serum are potential PD markers. These may help identify patients that may benefit from an elective, early induction of labor at term, thereby potentially reducing morbidity and mortality. However, their value in terms of the optimal date of delivery must first be determined in randomized controlled trials on a large number of cases.

Performance of sFlt-1/PIGF Ratio for the Prediction of Perinatal Outcome in Obese Pre-Eclamptic Women.

Obese women are at high risk of developing pre-eclampsia (PE). As an altered angiogenic profile is characteristic for PE, measurement of soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PIGF) ratio in the maternal serum can be helpful for PE diagnosis, as well as for adverse perinatal outcome (APO) prediction. There is growing evidence that obesity might influence the level of sFlt-1/PIGF and, therefore, the aim of the study was the evaluation of sFlt-1/PIGF as an APO predictor in obese women with PE. Pre-eclamptic women who had an sFlt-1/PIGF measurement at the time of diagnosis were retrospectively included. Women were classified according to their pre-pregnancy body mass index (BMI) as normal weight (BMI < 25 kg/m2), overweight (BMI > 25−29.9 kg/m2) or obese (BMI ≥ 30 kg/m2). APO was defined as the occurrence of one of the following outcomes: Small for gestational age, defined as a birthweight < 3rd centile, neonatal mortality, neonatal seizures, admission to neonatal unit required (NICU) or respiratory support. A total of 141 women were included. Of them, 28 (20%) patients were obese. ROC (receiver operating characteristic) analysis revealed a high predictive value for sFlt-1/PIGF and APO across the whole study cohort (AUC = 0.880, 95% CI: 0.826−0.936; p < 0.001). However, the subgroup of obese women showed a significantly lower level of sFlt-1 and, therefore, the performance of sFlt-1/PIGF as APO predictor was poorer compared to normal or overweight PE women (AUC = 0.754, 95% CI: 0.552−0.956, p = 0.025). In contrast to normal or overweight women, a ratio of sFlt-1/PIGF < 38 could not rule out APO in women with obesity.