Operating during pregnancy: A needs assessment among surgical residents in Austria.

In Austria, female physicians must immediately disrupt their surgical training as soon as their pregnancy is announced. In Germany, surveys on the topic of "female surgeons performing surgery during pregnancy" led to a reform of the German Maternity Protection Act, which came into force on January 1, 2018, and allows female physicians to perform risk-adapted surgery during pregnancy at their own request. However, in Austria, such reform is still pending. The study aimed i) to assess the current situation of how pregnant female surgeons handle their training under the actual restrictive legislature in Austria, especially in context of operative activity, and ii) to identify needs for improvements. Therefore, a nation-wide online survey, initiated by the Austrian Society for Gynecology and Obstetrics and the Young Forum of the Austrian Society of Gynecology and Obstetrics, was performed from June 1 to December 24, 2021, among employed physicians working in surgical specialties. To conduct a general needs assessment, the questionnaire was made available to both female and male physicians in all positions. In total, 503 physicians participated in the survey, of which 70.4% (n = 354) were women and 29.6% (n = 149) were men. The majority of the women (61.3%) were undergoing residency training at the time of their pregnancy. The announcement of the pregnancy to the supervisor(s) occurred on average in the 13th week of gestation (week 2-40). Before that, pregnant female physicians spent an average of 10 h per trimester (first trimester: 0-120 h; second trimester: 0-100 h) in the operating room. The main reason for women to continue surgical activity despite their (yet unreported) pregnancy was "own request". 93% (n = 469) of the participants explicitly wished to be able to perform surgical activities in a safe setting during pregnancy. This response was independent of gender (p = 0.217), age (p = 0.083), specialty (p = 0.351), professional position (p = 0.619), and previous pregnancy (p = 0.142). In conclusion, there is an urgent need to offer female surgeons the possibility of continuing surgical activities during pregnancy. This handling would significantly increase the career opportunities for women who want to build up both a successful career and a family life.

Outcome of Fetal Dysrhythmias with and without Extracardiac Anomalies.

Fetal dysrhythmias are common abnormalities, which can be categorized into three types: rhythm irregularities, tachyarrhythmias, and bradyarrhythmias. Fetal arrhythmias, especially in high-risk pregnancies, require special monitoring and treatment. The aim of this study was to assess the stillbirth and early and late neonatal mortality rates for pregnancies complicated by fetal dysrhythmias from one single tertiary referral center from 2000 to 2022. Of the 1018 fetuses with congenital heart disease, 157 (15.42%) were evaluated in this analysis. Seventy-four (46.7%) fetuses had bradyarrhythmias, 51 (32.5%) tachyarrhythmias, and 32 (20.4%) had rhythm irregularities. Additional structural heart defects were detected in 40 (25.3%) fetuses and extracardiac anomalies in 29 (18.4%) fetuses. Thirteen (8.2%) families opted for termination of the pregnancy. Eleven (7.6%), out of 144 continued pregnancies ended in spontaneous intrauterine fetal death (IUFD). Neonatal death was observed in nine cases (5.7%), whereas three (1.9%) died within the first 7 days of life. Although most intrauterine fetal deaths occurred in pregnancies with fetal bradyarrhythmia, neonatal death was observed more often in fetuses with tachyarrhythmia (8.5%). The presence of extracardiac anomalies, congenital heart disease (CHD), and Ro-antibodies are predictive factors for the occurrence of IUFD. Rhythm irregularities without any other risk factor do not present higher risks of adverse perinatal outcome.

SARS-CoV-2 variant-related abnormalities detected by prenatal MRI: a prospective case-control study.

Background: There are known complications for fetuses after infection with SARS-CoV-2 during pregnancy. However, previous studies of SARS-CoV-2 in pregnancy have largely been limited to histopathologic studies of placentas and prenatal studies on the effects of different SARS-CoV-2 variants are scarce to date. To examine the effects of SARS-CoV-2 variants on the placenta and fetus, we investigated fetal and extra-fetal structures using prenatal MRI. Methods: For this prospective case-control study, two obstetric centers consecutively referred pregnant women for prenatal MRI after confirmed SARS-CoV-2 infection. Thirty-eight prenatal MRI examinations were included after confirmed infection with SARS-CoV-2 and matched 1:1 with 38 control cases with respect to sex, MRI field strength, and gestational age (average deviation 1.76 ± 1.65, median 1.5 days). Where available, the pathohistological examination and vaccination status of the placenta was included in the analysis. In prenatal MRI, the shape and thickness of the placenta, possible lobulation, and vascular lesions were quantified. Fetuses were scanned for organ or brain abnormalities. Findings: Of the 38 included cases after SARS-CoV-2 infection, 20/38 (52.6%) were infected with pre-Omicron variants and 18/38 (47.4%) with Omicron. Prenatal MRIs were performed on an average of 83 days (±42.9, median 80) days after the first positive PCR test. Both pre-Omicron (P = .008) and Omicron (P = .016) groups showed abnormalities in form of a globular placenta compared to control cases. In addition, placentas in the pre-Omicron group were significantly thickened (6.35, 95% CI .02-12.65, P = .048), and showed significantly more frequent lobules (P = .046), and hemorrhages (P = .002). Fetal growth restriction (FGR) was observed in 25% (n = 5/20, P = .017) in the pre-Omicron group. Interpretation: SARS-CoV-2 infections in pregnancy can lead to placental lesions based on vascular events, which can be well visualized on prenatal MRI. Pre-Omicron variants cause greater damage than Omicron sub-lineages in this regard. Funding: Vienna Science and Technology Fund.

Written Briefing and Oral Counseling Increase the Willingness to Receive the SARS-CoV-2 Vaccination among Women in Puerperium: A Qualitative Prospective Cohort Study.

(1) Background: Vaccination rates for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) are low in Austria. International obstetric societies recommend the SARS-CoV-2 mRNA vaccination for women in puerperium. (2) Methods: A prospective two-stage cohort study was conducted at the Medical University of Vienna between October 2022 and December 2022. Firstly, women in puerperium were assigned to the evaluation group (step 1), and secondly, another cohort of unvaccinated women were randomly assigned to study group A (written briefing) or B (written and oral briefing) (step 2). We evaluated the vaccination status among women in the evaluation group and the willingness to receive the vaccination in all three cohorts. (3) Results: We included 217 women in puerperium (evaluation: n = 69, A: n = 68; B: n = 80). In the evaluation group, 66.7% (n = 46/69) of the women were unvaccinated. A total of 45.7% (21/46) of the unvaccinated women categorically declined the SARS-CoV-2 vaccination. A total of 26.5% (n = 18/68) of women in study group A, and 43.8% (n = 35/80) of women in study group B expressed their willingness to receive the vaccination (p = 0.029). There were no differences in willingness to receive the vaccination between different age strata of women in study groups A and B. (D) Conclusion: Our qualitative data demonstrate a benefit from oral counseling in addition to written briefing in order to increase the willingness to receive the vaccination among women in puerperium.

Gestational Diabetes Mellitus in Pregnant Women with Beta-Thalassemia Minor: A Matched Case-Control Study.

Pregnancy in women with thalassemia minor is considered safe. However, a higher incidence of maternal and neonatal complications in women with the disorder has been reported in the literature. This study aimed to determine whether there is an increased risk of gestational diabetes mellitus (GDM) in pregnant women with beta-thalassemia minor. We conducted a retrospective matched case-control study of 230 pregnant women who delivered at the Department of Obstetrics and Feto-Maternal Medicine at the Medical University of Vienna between the years 2008 and 2020, whereof 115 women had beta-thalassemia minor. We found no significant difference in the occurrence of GDM between the case group and control group of age and BMI-matched healthy women. However, we observed a significantly lower hemoglobin (Hb) and hematocrit (Ht) level during the first, the second, and the third trimesters of pregnancy, and postpartum (all: p < 0.001) among women with beta-thalassemia minor compared to the healthy controls. Neonates of women with beta-thalassemia were more likely to experience post-natal jaundice and excessive weight loss (p < 0.001). We conclude that GDM is not more likely to occur in pregnant women with beta-thalassemia minor. However, clinicians should be made aware of the risk of adverse maternal and neonatal outcomes. Furthermore, women with beta-thalassemia minor should undergo regular laboratory screening and multidisciplinary pregnancy care.

Awareness of obstetricians for long-term risks in women with a history of preeclampsia or HELLP syndrome.

PURPOSE: Hypertensive disorders of pregnancy are still a leading cause of maternal and neonatal morbidity and mortality worldwide. Women with a history of preeclampsia have an increased risk for future cardiovascular and cerebrovascular disease, renal disease as well as diabetes mellitus. There is little knowledge on postpartum risk management. The aim of this study was to assess follow-up care for patients after pre-eclampsia or HELLP syndrome. METHODS: This questionnaire-based cross-sectional study aimed to evaluate the current recommendations of obstetricians in Austria regarding follow-up care, long-term risk counselling and risk of recurrence in future pregnancies after preeclampsia or HELLP syndrome. Data were collected using a survey, based on recommendations given by three substantial guidelines on hypertensive disorders of pregnancy, which was distributed via e-mail to 69 public obstetric departments in Austria. Each obstetric department was required to answer one questionnaire per local protocol. RESULTS: Our results revealed that of the 48 participating hospitals most obstetricians are aware of the importance of follow-up care for women after a pregnancy complicated by preeclampsia. Our data show that most physicians counselled patients about the future cardiovascular health risks associated with preeclampsia or HELLP syndrome (79.2%). Most obstetricians recommended lifestyle modification (77.1%) and continued blood pressure measurements (97.9%). All centers stated to counsel about the risk of recurrence (100%). However, counselling regarding follow-up care to exclude kidney damage (37.5%) and underlying diseases like thrombophilia (39.6%) were less prioritized. CONCLUSIONS: We were able to show that counselling concerning the risk of long-term cardiovascular disease and risk of recurrence after a pregnancy complicated by preeclampsia or HELLP syndrome has been established in obstetric departments in public hospitals. Regarding the evaluation of underlying chronic diseases such as thrombophilia or renal disease, as well as counselling on the future risk of renal disease is still improvable according to our data. Further evaluation of follow-up care after hypertensive disorders of pregnancy in the outpatient and private sector and implementation of structured guidelines for follow-up, as well as screening for cardiovascular disease are necessary to ensure adequate risk management and to provide opportunities for prevention.

Comparison of Ultrasound Descriptors of Abnormally Invasive Placenta (AIP) over the Course of the Second and Third Trimester-Is an Increase Verifiable?

Limited data exist regarding the course of abnormally invasive placentation (AIP) (=placenta accreta spectrum (PAS)) during the 2nd and 3rd trimester, although this knowledge would be important for optimal patient care. In this retrospective single-center longitudinal cohort study, potential aggravation of AIP was evaluated in 37 patients with ultrasound (US) pictures stored on a minimum of two visits. Five raters, blinded to diagnosis and gestational age, judged the degree of AIP as recommended by the International Society for PAS. The probability of invasiveness was estimated as absent, low, intermediate, severe (0-3 points), the extent as absent, focal, diffuse (0-2 points), and the presence and appearance of each US-sign as absent, mild, severe (0-3 points). None of the 10 judged signs appeared more severe (p ≥ 0.41) with progressing pregnancy. Neither the number of positively scored US-signs (earlier scan; 6.14 ± 2.06, later scan; 5.94 ± 2.16; p = 0.28), nor the estimated probability & extent of AIP rose (3.69 ± 1.15 vs. 3.67 ± 1.22; p = 1.0). Test-retest reliability corroborated excellent agreement between visits (mean number of positive US-signs ICC (3,1) = 0.94, 95% CI 0.91-0.97; p < 0.0001). Overall, there was no clinically detectable increase in invasiveness over the course of the 2nd and 3rd trimester. This should be further evaluated in prospective studies.

Prognostic Value of Angiogenic Markers in Pregnant Women With Chronic Hypertension.

Background Women with chronic hypertension face a 5- to 6-fold increased risk of developing preeclampsia compared with normotensive women. Angiogenic markers, especially soluble fms-like kinase 1 (sFlt-1) and placental growth factor (PlGF), were identified as clinically useful markers predicting the development of preeclampsia, but data on the prediction of superimposed preeclampsia are scarce. Therefore, we aimed to evaluate the predictive value of the sFlt-1/PlGF ratio for delivery because of superimposed preeclampsia in women with chronic hypertension. Methods and Results This retrospective study included 142 women with chronic hypertension and suspected superimposed preeclampsia. Twenty-seven women (19.0%) delivered because of maternal indications only, 17 women (12.0%) because of fetal indications primarily, and 98 women (69.0%) for other reasons. Women who both delivered because of maternal indications and for fetal indications had a significantly higher sFlt-1/PlGF ratio (median 99.9 and 120.2 versus 7.3, respectively, P<0.001 for both) and lower PlGF levels (median 73.6 and 53.3 versus 320.0 pg/mL, respectively, P<0.001 for both) compared with women who delivered for other reasons. SFlt-1/PlGF ratio and PlGF were strong predictors for delivery because of superimposed preeclampsia, whether for maternal or fetal indications (P<0.05). Half of women with angiogenic imbalance (sFlt-1/PlGF ratio ≥85 or PlGF levels <100 pg/mL) delivered because of maternal or fetal indications within 1.6 weeks (95% CI, 1.0-2.4 weeks). Conclusions Angiogenic marker imbalance in women with suspected superimposed preeclampsia can predict delivery because of maternal and fetal indications related to superimposed preeclampsia and is associated with a significantly shorter time to delivery interval.

Performance of antenatal imaging to predict placenta accreta spectrum degree of severity.

INTRODUCTION: In cases of placenta accreta spectrum, a precise antenatal diagnosis of the suspected degree of invasion is essential for the planning of individual management strategies at delivery. The aim of this work was to evaluate the respective performances of ultrasonography and magnetic resonance imaging for the antenatal assessment of the severity of placenta accreta spectrum disorders included in the database. The secondary objective was to identify descriptors related to the severity of placenta accreta spectrum disorders. MATERIAL AND METHODS: All the cases included in the database for which antenatal imaging data were available were analyzed. The rates of occurrence of each ultrasound and magnetic resonance imaging descriptor were reported and compared between the Group "Accreta-Increta" (FIGO grades 1 & 2) and the Group "Percreta" (FIGO grade 3). RESULTS: Antenatal imaging data were available for 347 women (347/442, 78.5%), of which 105 were included in the Group "Accreta - Increta" (105/347, 30.2%) and 213 (213/347, 61.4%) in the Group "Percreta". Magnetic resonance imaging was performed in addition to ultrasound in 135 women (135/347, 38.9%). After adjustment for all ultrasound descriptors in multivariate analysis, only the presence of a bladder wall interruption was associated with a significant higher risk of percreta (Odds ratio 3.23, Confidence interval 1.33-7.79). No magnetic resonance imaging sign was significantly correlated with the degree of severity. CONCLUSIONS: The performance of ultrasound and magnetic resonance imaging to discriminate mild from severe placenta accreta spectrum disorders is very poor. To date, the benefit of additional magnetic resonance imaging has not been demonstrated.

Angiogenic markers and their longitudinal change for predicting adverse outcomes in pregnant women with chronic hypertension.

BACKGROUND: Women with chronic hypertension are at increased risk for adverse maternal and perinatal outcomes. Maternal serum angiogenic markers, such as soluble fms-like tyrosine kinase 1 and placental growth factor, can be used to triage women with suspected preeclampsia. However, data about these markers in pregnant women with chronic hypertension are scarce. OBJECTIVE: We aimed to evaluate the predictive accuracy of maternal serum levels of soluble fms-like tyrosine kinase 1, placental growth factor, and their ratio for predicting adverse maternal and perinatal outcomes in women with chronic hypertension. STUDY DESIGN: This was a retrospective analysis of prospectively collected data from January 2013 to October 2019 at the University of Vienna Hospital, Vienna, Austria. The inclusion criteria were pregnant women with chronic hypertension and suspected preeclampsia. The primary outcome of this study was the prognostic performance of angiogenic markers for the prediction of adverse maternal and perinatal outcomes in pregnant women with chronic hypertension. The accuracy of angiogenic markers for predicting adverse composite outcomes was assessed with a binomial logistic regression. The accuracy of each marker was assessed using receiver operating characteristics curves and area under the curve values. Area under the curve values were compared using De Long's test. RESULTS: Of the 145 included women with chronic hypertension and suspected superimposed preeclampsia, 26 (17.9%) women developed complications (ie, composite adverse maternal or fetal outcomes) within 1 week of assessment (average gestational age at assessment, 29.9 weeks) and 35 (24.1%) developed complications at any time (average gestational age at assessment, 30.1 weeks). In women who developed complications at any time, the median maternal serum soluble fms-like tyrosine kinase-1 to placental growth factor ratio was 149.4 (interquartile range, 64.6-457.4) compared with 8.0 (interquartile range, 3.37-41.2) for women who did not develop complications (P<.001). The area under the curve values for the maternal serum soluble fms-like tyrosine kinase-1 to placental growth factor ratio Z-score (0.95; 95% confidence interval, 0.90-0.99) and placental growth factor level Z-score (0.94; 95% confidence interval, 0.88-0.99) for predicting complications within 1 week of assessment were very high. The area under the curve values for new-onset edema (0.61; 95% confidence interval, 0.52-0.70), proteinuria (0.62; 95% confidence interval, 0.52-0.71), high mean arterial pressure (0.52; 95% confidence interval, 0.50-0.54), and other symptoms of preeclampsia (0.57; 95% confidence interval, 0.49-0.65) were all significantly lower than for the angiogenic markers (P<.001 for all). Women who had an angiogenic imbalance and/or proteinuria had the highest rate of complications (28/57, 49.1%). The rate of complications in women with an angiogenic imbalance and/or proteinuria was significantly higher than in women with either proteinuria, other symptoms, or intrauterine growth restriction in the absence of an angiogenic imbalance (49.1% vs 16.7%; P=.039). The highest positive and negative predictive values for predicting adverse outcomes were demonstrated by an angiogenic imbalance and/or proteinuria criteria with a positive predictive value of 49.1% (95% confidence interval, 50.4%-57.9%) and a negative predictive value of 92% (95% confidence interval, 85.5%-95.8%). Longitudinal changes in measurements of the gestational age-corrected ratio of soluble fms-like tyrosine kinase-1 to placental growth factor up to the last measurement had a significantly higher area under the curve value than the last measurement alone (area under the curve, 0.95; 95% confidence interval, 0.92-0.99 vs 0.87; 95% confidence interval, 0.79-0.95; P=.024) CONCLUSION: Maternal serum angiogenic markers are superior to clinical assessment in predicting adverse maternal and perinatal outcomes in pregnant women with chronic hypertension. Repeated measurements of the ratio of soluble fms-like tyrosine kinase-1 to placental growth factor seems beneficial given the better predictive accuracy compared with a single measurement alone. The use of angiogenic makers should be implemented in clinical management guidelines for pregnant women with chronic hypertension.

Maternal and neonatal outcomes in planned versus emergency cesarean delivery for placenta accreta spectrum: A multinational database study.

INTRODUCTION: Placenta accreta spectrum (PAS) is a condition often resulting in severe maternal morbidity. Scheduled delivery by an experienced team has been shown to improve maternal outcomes; however, the benefits must be weighed against the risk of iatrogenic prematurity. The aim of this study is to investigate the rates of emergency delivery seen for antenatally suspected PAS and compare the resulting outcomes in the 15 referral centers of the International Society for PAS (IS-PAS). MATERIAL AND METHODS: Fifteen centers provided cases between 2008 and 2019. The women included were divided into two groups according to whether they had a planned or an emergency cesarean delivery. Delivery was defined as "planned" when performed at a time and date to suit the team. All the remaining cases were classified as "emergency". Maternal characteristics and neonatal outcomes were compared between the two groups according to gestation at delivery. RESULTS: In all, 356 women were included. Of these, 239 (67%) underwent a planned delivery and 117 (33%) an emergency delivery. Vaginal bleeding was the indication for emergency delivery in 41 of the 117 women (41%). There were no significant differences in terms of blood loss, transfusion rates or major maternal morbidity between planned and emergency deliveries. However, the rate of maternal intensive therapy unit admission was increased with emergency delivery (45% vs 33%, P = .02). Antepartum hemorrhage was the only independent predictor of emergency delivery (aOR: 4.3, 95% confidence interval 2.4-7.7). Emergency delivery due to vaginal bleeding was more frequent with false-positive cases (antenatally suspected but not confirmed as PAS at delivery) and the milder grades of PAS (accreta/increta). The rate of infants experiencing any major neonatal morbidity was 25% at 34+1 to 36+0  weeks and 19% at >36+0  weeks. CONCLUSIONS: Emergency delivery in centers of excellence did not increase blood loss, transfusion rates or maternal morbidity. The single greatest risk factor for emergency delivery was antenatal hemorrhage. When adequate expertise and resources are available, to defer delivery in women with no significant antenatal bleeding and no risk factors for pre-term birth until >36+0  weeks can be considered to improve fetal outcomes. Further studies are needed to investigate this fully.

Selective Fetal Growth Restriction in Dichorionic Twin Pregnancies: Diagnosis, Natural History, and Perinatal Outcome.

This study aims to evaluate the natural history, disease progression, and outcomes in dichorionic twins with selective fetal growth restriction (sFGR) according to different diagnostic criteria and time of onset. Dichorionic twins seen from the first trimester were included. sFGR was classified according to the Delphi consensus, and was compared to the outcomes of those classified by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) diagnostic criteria. Early sFGR occurred before 32-weeks, and late sFGR after 32-weeks. Disease progression, neonatal outcomes such as gestation at delivery, birthweight, neonatal unit (NNU) admission, and morbidities were compared. One-hundred twenty-three of 1053 dichorionic twins had sFGR, where 8.4% were classified as early sFGR, and 3.3% were late sFGR. Disease progression was seen in 36%, with a longer progression time (5 vs. 1 week) and higher progression rate (40% vs. 26%) in early sFGR. Perinatal death was significantly higher in the sFGR than the non-sFGR group (24 vs. 16 per 1000 births, p = 0.018), and those with early sFGR had more NNU admissions than late sFGR (p = 0.005). The ISUOG diagnostic criteria yielded a higher number of sFGR than the Delphi criteria, but similar outcomes. sFGR have worse perinatal outcomes, with early onset being more prevalent. Use of the Delphi diagnostic criteria can reduce over-diagnosis of sFGR and avoid unnecessary intervention.

The Prognostic Value of Angiogenic Markers in Twin Pregnancies to Predict Delivery Due to Maternal Complications of Preeclampsia.

The sFlt-1 (soluble fms-like tyrosine kinase-1), PlGF (placental growth factor), and their ratio are useful for predicting delivery because of preeclampsia in singleton pregnancies. Evidence on the utility of sFlt-1/PlGF ratio in twin pregnancies is lacking. We aimed to evaluate the predictive value of sFlt-1/PlGF ratio for delivery because of preeclampsia in twins. A retrospective data analysis of 164 twin pregnancies with suspected preeclampsia was performed. The sFlt-1/PlGF ratio, which was known to clinicians, was significantly higher in women who delivered within 1 and 2 weeks compared with those who did not (median: 98.9 and 84.2 versus 23.5 pg/mL, respectively; P<0.001). The area under the curve values sFlt-1/PlGF ratio levels were 0.88 (95% CI, 0.83-0.84) and 0.88 (95% CI, 0.83-0.93) for predicting delivery because of preeclampsia within 1 and 2 weeks of blood sampling, respectively. The predictive accuracy of sFlt-1/PlGF was independent of gestational age at sampling and chorionicity (P>0.100 for interaction). The area under the curve values of sFlt-1/PlGF were significantly higher than for PlGF alone (mean 0.88 and 0.88 versus 0.81 and 0.80) for predicting delivery because of preeclampsia within 1 and 2 weeks of blood sampling (P=0.055 and 0.001, respectively). sFlt-1/PlGF ratio lower than 38 was able to rule-out delivery within 1 and 2 weeks with a negative predictive value of 98.8% and 96.4% for delivery because of preeclampsia within 1 and 2 weeks, respectively. A cutoff of 38 is applicable for ruling out delivery because of preeclampsia in twin pregnancies.

Evidence-based guidelines for the management of abnormally invasive placenta: recommendations from the International Society for Abnormally Invasive Placenta.

The worldwide incidence of abnormally invasive placenta is rapidly rising, following the trend of increasing cesarean delivery. It is a heterogeneous condition and has a high maternal morbidity and mortality rate, presenting specific intrapartum challenges. Its rarity makes developing individual expertise difficult for the majority of clinicians. The International Society for Abnormally Invasive Placenta aims to improve clinicians' understanding and skills in managing this difficult condition. By pooling knowledge, experience, and expertise gained within a variety of different healthcare systems, the Society seeks to improve the outcomes for women with abnormally invasive placenta globally. The recommendations presented herewith were reached using a modified Delphi technique and are based on the best available evidence. The evidence base for each is presented using a formal grading system. The topics chosen address the most pertinent questions regarding intrapartum management of abnormally invasive placenta with respect to clinically relevant outcomes, including the following: definition of a center of excellence; requirement for antenatal hospitalization; antenatal optimization of hemoglobin; gestational age for delivery; antenatal corticosteroid administration; use of preoperative cystoscopy, ureteric stents, and prophylactic pelvic arterial balloon catheters; maternal position for surgery; type of skin incision; position of the uterine incision; use of interoperative ultrasound; prophylactic administration of oxytocin; optimal method for intraoperative diagnosis; use of expectant management; adjuvant therapies for expectant management; use of local surgical resection; type of hysterectomy; use of delayed hysterectomy; intraoperative measures to treat life-threatening hemorrhage; and fertility after conservative management.

Maternal serum mitochondrial DNA (mtDNA) levels are elevated in preeclampsia - A matched case-control study.

OBJECTIVE: Oxidative stress and mitochondrial dysfunction may play a crucial role in preeclampsia (PE). The aim of this study was to investigate differences in maternal levels of serum-mitochondrial (mt) DNA, a proposed biomarker for mitochondrial dysfunction, in women with PE compared to healthy pregnant women. STUDY DESIGN: Using samples obtained from the prospective Biobank study, we measured serum-mtDNA levels in pregnant women diagnosed with PE and in women with uneventful pregnancies, matched for gestational and maternal age, BMI, and smoking status. In a second step, we performed a generalized linear model to detect associations between mtDNA-serum-levels and certain conditions during pregnancy. RESULTS: Mean mtDNA levels were significantly higher in PE (n = 20) than in matched controls (n = 20) and were 0.00767 (SD 0.00255) U/L and 0.00513 (SD 0.00458) U/L, respectively (p = 0.038). We did not find a significant correlation between higher mtDNA levels and early onset PE, IUGR, maternal age, or maternal BMI. Interestingly, increased mtDNA levels were significantly associated with female fetal sex (p = 0.003). CONCLUSION: Our findings strengthen the hypothesis postulating that oxidative stress and mitochondrial dysfunction are key factors in the pathophysiology of PE. More prospective studies are highly warranted to further investigate the role of mtDNA in PE and assess the usefulness as a possible biomarker for PE.

hsa-miRNA-154-5p expression in plasma of endometriosis patients is a potential diagnostic marker for the disease.

RESEARCH QUESTION: As microRNA (miRNA) are stable in circulation, this study tested whether they could serve as putative non-invasive biomarkers for endometriosis, and their expression differences between endometriosis patients and controls. It also addressed whether the combination of differently expressed miRNA together with clinical parameters in a statistical model could distinguish between endometriosis patients and controls. DESIGN: This prospective cohort study explored the possibility of using changes in extracellular miRNA spectra in plasma of 51 patients with endometriosis compared with 41 controls combined with clinical data as non-invasive biomarkers for the disease. The project was divided into three different phases for biomarker screening, discovery and validation. The differences in expression levels of plasma miRNA obtained from women with and without endometriosis were analysed with quantitative PCR-based microarrays. The diagnostic performance of the selected individual and/or combined differentially expressed miRNA candidates and clinical parameters was assessed using in silico bioinformatics modelling and receiver operating characteristic curve analysis. RESULTS: Data showed that a specific plasma miRNA signature is associated with endometriosis and that hsa-miR-154-5p, which alone or in combination with hsa-miR-196b-5p, hsa-miR-378a-3p, and hsa-miR-33a-5p and the clinical parameters of body mass index and age, are potentially applicable for non-invasive diagnosis of the disease. Changes in the levels of expression of certain circulating plasma miRNA also occurred within the phases of the menstrual cycle. CONCLUSIONS: miRNA seem to be promising candidates for the non-invasive diagnosis of endometriosis. Further, other clinical parameters may help in distinguishing women suffering from endometriosis from healthy individuals.

Longitudinal assessment of HLA and MIC-A antibodies in uneventful pregnancies and pregnancies complicated by preeclampsia or gestational diabetes.

The significance of antibodies directed against paternal epitopes in the context of obstetric disorders is discussed controversially. In this study anti-HLA and anti-MIC-A antibodies were analysed in sera of women with uneventful pregnancy (n = 101), preeclampsia (PE, n = 55) and gestational diabetes (GDM, n = 36) using antigen specific microbeads. While two thirds of the women with uneventful pregnancy or GDM were HLA and MIC-A antibody positive in gestational week 11 to 13 with a modest increase towards the end of pregnancy, women with PE showed an inverse kinetic: 90% were HLA antibody positive in gestational week 11 to 13 and only 10% showed HLA reactivities at the end of the pregnancy. HLA antibody binding strength was more pronounced in gestational week 14 to 17 in patients with PE compared to women with uneventful pregnancy (maximum median fluorescence intensity of the highest ranked positive bead 7403, IQR 2193-7938 vs. 1093, IQR 395-5689; p = 0.04) and was able to predict PE with an AUC of 0.80 (95% CI 0.67-0.93; p = 0.002). Our data suggest a pathophysiological involvement of HLA antibodies in PE. HLA antibody quantification in early pregnancy may provide a useful tool to increase diagnostic awareness in women prone to develop PE.

The usefulness of CYFRA 21-1 to diagnose and predict preeclampsia: a nested case-control study.

BACKGROUND: The ability to identify patients at risk for developing preeclampsia is important for preventing morbidity and mortality in both the mother and child. Although CYFRA 21-1 (a fragment of Cytokeratin 19) is considered a promising biomarker for diagnosing preeclampsia, little is known regarding the levels of CYFRA 21-1 during pregnancy. Here, we measured serum CYFRA 21-1 levels in women with an uneventful pregnancy and in women whose pregnancy was complicated by preeclampsia. Furthermore we evaluated whether maternal CYFRA 21-1 levels can be used to predict and/or diagnose preeclampsia. METHODS: Longitudinal, sequential blood samples were collected prospectively at seven predetermined visits during pregnancy. Maternal CYFRA 21-1 levels were measured in 50 women with an uneventful pregnancy (control group) and in 10 asymptomatic women whose pregnancy was later complicated by preeclampsia (PE_long group). In addition, CYFRA 21-1 levels were measured from a single sample collected from a separate group of 50 pregnant women with symptomatic preeclampsia (PE_state group). RESULTS: The CYFRA 21-1 levels were significantly higher in the PE_state group compared to the control group (p < 0.001). In the PE_long group, CYFRA 21-1 levels were lower from gestational week 11 through 17, but were higher than the control group from gestational weeks 18 through 36. Out of the ROC curves that were calculated to investigate the predictive and diagnostic properties of CYFRA 21-1 levels for preeclampsia, the ROC curve for diagnosing preeclampsia in gestational week 28-32 showed the largest AUC of 0.92, at a cut-off point of 3.1 ng/ml, leading to sensitivity of 92 % and specificity of 80 %. CONCLUSIONS: The elevated serum levels of CYFRA 21-1 observed in both groups of women with preeclampsia may reflect endothelial damage and/or dysfunction. Our results suggest that maternal serum CYFRA 21-1 is a promising biomarker for diagnosing preeclampsia. Although its value for predicting the long-term occurrence of subsequent preeclampsia may be limited, our findings indicate a trend towards elevated maternal CYFRA 21-1 levels preceding the short-term occurrence of preeclampsia in asymptomatic women. Additional prospective longitudinal studies are needed in order to determine the value of measuring maternal serum CYFRA 21-1 in predicting preeclampsia.

The Serum Levels of the Soluble Factors sCD40L and CXCL1 Are Not Indicative of Endometriosis.

Endometriosis is a benign but troublesome gynecological condition, characterized by endometrial-like tissue outside the uterine cavity. Lately, the discovery and validation of noninvasive diagnostic biomarkers for endometriosis is one of the main priorities in the field. As the disease elicits a chronic inflammatory reaction, we focused our interest on two factors well known to be involved in inflammation and neoplastic processes, namely, soluble CD40 Ligand and CXCL1, and asked whether differences in the serum levels of sCD40L and CXCL1 in endometriosis patients versus controls can serve as noninvasive disease markers. A total of n = 60 women were included in the study, 31 endometriosis patients and 29 controls, and the serum levels of sCD40L and CXCL1 were measured by enzyme-linked immunosorbent assay. Overall, there were no statistically significant differences in the levels of expression of both sCD40L and CXCL1 between patients and controls. This study adds useful clinical data showing that the serum levels of the soluble factors sCD40L and CXCL1 are not associated with endometriosis and are not suitable as biomarkers for disease diagnosis. However, we found a trend toward lower levels of sCD40L in the deep infiltrating endometriosis subgroup making it a potentially interesting target worth further investigation.

Detection of circulating trophoblast particles in maternal blood using density gradient centrifugation in preeclampsia and in normotensive pregnancies.

OBJECTIVE: Preeclampsia (PE) is a frequent pregnancy-related disease and a major cause of maternal and fetal morbidity and mortality. Despite that, exact mechanisms of its pathophysiology remain largely unknown. In pregnancies complicated by PE, changes in the regulation of apoptosis seem to result in increased apoptotic shedding of trophoblast particles (TPs) into maternal circulation. Since the number of TP in peripheral blood is low, their detection necessitates pre-analytical enrichment. METHODS: In this prospective multicenter pilot study we aimed to analyze TP in peripheral blood of 29 women with PE and of 13 unaffected controls using the OncoQuick®plus system for cell enrichment. Using immunocytochemistry, slides were evaluated microscopically for TP. Statistical analyses were performed using Welch's t-test or Fisher's exact test. RESULTS: TP were detected in 10 (34.5%) women with PE and in two (15.4%) of unaffected controls. More than one TP were only found in PE. Comparing the mean counts of TP between groups, we detected significantly more TP in PE (p = 0.046). CONCLUSIONS: The OncoQuick®plus system can be applied to detect TP in both women with PE and in normotensive pregnancies. Longitudinal studies investigating the role of TP as a screening method for patients at risk for PE are warranted.