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Background: Internationally, potential effects of national SARS-CoV-2-related lockdowns on stillbirth rates have been reported, but data for Germany, including risk factors for fetal pregnancy outcome, are lacking. The aim of this study is to compare the stillbirth rates during the two first lockdown periods in 2020 with previous years from 2010 to 2019 in a large Bavarian cohort., Methods: This study is a secondary analysis of the Bavarian perinatal data from 2010 to 2020, including 349,245 births. Univariate and multivariable regression analyses were performed to investigate the effect of two Bavarian lockdowns on the stillbirth rate in 2020 compared to the corresponding periods from 2010 to 2019., Results: During the first lockdown, the stillbirth rate was significantly higher compared to the reference period (4.04 vs. 3.03 stillbirths per 1000 births; P = 0.03). After adjustment for seasonal and long-term trends, this effect can no longer be observed (P = 0.2). During the second lockdown, the stillbirth rate did not differ in univariate (3.46 vs. 2.93 stillbirths per 1000 births; P = 0.22) as well as in multivariable analyses (P = 0.68), compared to the years 2010 to 2019., Conclusion: After adjustment for known long-term effects, in this study we did not find evidence that the two Bavarian lockdowns had an effect on the rate of stillbirths., (© 2022. The Author(s).)

Background: High mammographic density (MD) is a risk factor for the development of breast cancer (BC). Changes in MD are influenced by multiple factors such as age, BMI, number of full-term pregnancies and lactating periods. To learn more about MD, it is important to establish non-radiation-based, alternative examination methods to mammography such as ultrasound assessments., Methods: We analyzed data from 168 patients who underwent standard-of-care mammography and performed additional ultrasound assessment of the breast using a high-frequency (12 MHz) linear probe of the VOLUSON ® 730 Expert system (GE Medical Systems Kretztechnik GmbH & Co OHG, Austria). Gray level bins were calculated from ultrasound images to characterize mammographic density. Percentage mammographic density (PMD) was predicted by gray level bins using various regression models., Results: Gray level bins and PMD correlated to a certain extent. Spearman's ρ ranged from - 0.18 to 0.32. The random forest model turned out to be the most accurate prediction model (cross-validated R 2 , 0.255). Overall, ultrasound images from the VOLUSON ® 730 Expert device in this study showed limited predictive power for PMD when correlated with the corresponding mammograms., Conclusions: In our present work, no reliable prediction of PMD using ultrasound imaging could be observed. As previous studies showed a reasonable correlation, predictive power seems to be highly dependent on the device used. Identifying feasible non-radiation imaging methods of the breast and their predictive power remains an important topic and warrants further evaluation. Trial registration 325-19 B (Ethics Committee of the medical faculty at Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany)., (© 2023. The Author(s).)

Background and Objectives : The aim of this study was to investigate the prediction of adverse perinatal outcomes using the cerebroplacental (CPR) and umbilicocerebral (UCR) ratios in different cohorts of singleton pregnancies. Materials and Methods : In this retrospective cohort study, we established our own Multiple of Median (MoM) for CPR and UCR. The predictive value for both ratios was studied in the following outcome parameters: emergency cesarean delivery, operative intervention (OI), OI due to fetal distress, 5-min Apgar < 7, admission to neonatal intensive care unit, and composite adverse perinatal outcome. The performance of the ratios was assessed in the following cohorts: total cohort (delivery ≥ 37 + 0 weeks gestation, all birth weight centiles), low-risk cohort (delivery ≥ 37 + 0 weeks gestation, birth weight ≥ 10. centile), prolonged pregnancy cohort (delivery ≥ 41 + 0 weeks gestation, birth weight ≥ 10. centile) and small-for-gestational-age fetuses (delivery ≥ 37 + 0 weeks gestation, birth weight < 10. centile). The underlying reference values for MoM were estimated using quantile regression depending on gestational age. Prediction performance was evaluated using logistic regression models assessing the corresponding Brier score, combining discriminatory power and calibration. Results : Overall, 3326 cases were included. Across all cohorts, in the case of a significant association between a studied outcome parameter and CPR, there was an association with UCR, respectively. The Brier score showed only minimal differences for both ratios. Conclusions : Our study provides further evidence regarding predictive values of CPR and UCR. The results of our study suggest that reversal of CPR to UCR does not improve the prediction of adverse perinatal outcomes.

Retention of circulating lipoproteins by their interaction with extracellular matrix molecules has been suggested as an underlying mechanism for atherosclerosis. We investigated the role of glypican-4 (GPC4), a heparan sulfate (HS) proteoglycan, in the development of endothelial dysfunction and plaque progression; Expression of GPC4 and HS was investigated in human umbilical vein/artery endothelial cells (HUVECs/HUAECs) using flow cytometry, qPCR, and immunofluorescent staining. Leukocyte adhesion was determined in HUVECs in bifurcation chamber slides under dynamic flow. The association between the degree of inflammation and GPC4, HS, and syndecan-4 expressions was analyzed in human carotid plaques; GPC4 was expressed in HUVECs/HUAECs. In HUVECs, GPC4 protein expression was higher in laminar than in non-uniform shear stress regions after a 1-day or 10-day flow ( p < 0.01 each). The HS expression was higher under laminar flow after a 1 day ( p < 0.001). Monocytic THP-1 cell adhesion to HUVECs was facilitated by GPC4 knock-down ( p < 0.001) without affecting adhesion molecule expression. GPC4 and HS expression was lower in more-inflamed than in less-inflamed plaque shoulders ( p < 0.05, each), especially in vulnerable plaque sections; Reduced expression of GPC4 was associated with atherogenic conditions, suggesting the involvement of GPC4 in both early and advanced stages of atherosclerosis.

Atherosclerotic lesions preferentially develop at bifurcations, characterized by non-uniform shear stress (SS). The aim of this study was to investigate SS-induced endothelial activation, focusing on stress-regulated mitogen-activated protein kinases (MAPK) and downstream signaling, and its relation to gap junction proteins, Connexins (Cxs). Human umbilical vein endothelial cells were exposed to flow ("mechanical stimulation") and stimulated with TNF-α ("inflammatory stimulation"). Phosphorylated levels of MAPKs (c-Jun N-terminal kinase (JNK1/2), extracellular signal-regulated kinase (ERK), and p38 kinase (p38K)) were quantified by flow cytometry, showing the activation of JNK1/2 and ERK. THP-1 cell adhesion under non-uniform SS was suppressed by the inhibition of JNK1/2, not of ERK. Immunofluorescence staining and quantitative real-time PCR demonstrated an induction of c-Jun and c-Fos and of Cx43 in endothelial cells by non-uniform SS, and the latter was abolished by JNK1/2 inhibition. Furthermore, plaque inflammation was analyzed in human carotid plaques ( n = 40) using immunohistochemistry and quanti-gene RNA-assays, revealing elevated Cx43 + cell counts in vulnerable compared to stable plaques. Cx43 + cell burden in the plaque shoulder correlated with intraplaque neovascularization and lipid core size, while an inverse correlation was observed with fibrous cap thickness. Our results constitute the first report that JNK1/2 mediates Cx43 mechanoinduction in endothelial cells by atheroprone shear stress and that Cx43 is expressed in human carotid plaques. The correlation of Cx43 + cell counts with markers of plaque vulnerability implies its contribution to plaque progression.

Objective:  To evaluate the influence of inaccurate sonographic fetal weight estimation in macrosomia on the mode of delivery and neonatal outcome (NO)., Methods:  In 14 633 pregnancies between 2002 and 2016, this retrospective study evaluated the association between sonographic fetal weight estimation, true birth weight (BW), mode of delivery (primary cesarean section [pCS], secondary cesarean section, vaginal delivery, and operative vaginal delivery rates) and NO parameters (5-min Apgar < 7, pH < 7.1, neonatal intensive care unit [NICU] admission, shoulder dystocia). Singleton pregnancies > 37 + 0 weeks with ultrasound-estimated fetal weight (EFW) within 7 days before delivery were included. The study population was divided into four groups: Group 1 (false-negative): EFW < 4000 g/BW ≥ 4000 g; Group 2 (true-positive): EFW ≥ 4000 g/BW ≥ 4000 g; Group 3 (false-positive): EFW ≥ 4000 g/BW < 4000 g; and Group 4 (true-negative): EFW < 4000 g/BW < 4000 g., Results:  As expected, the highest secondary cesarean section (sCS) rate was found in Group 2 (true-positive) (30.62 %), compared with only 17.68 % in Group 4 (true-negative). The sCS rate in the false-positive Group 3 was significantly higher (28.48 %) in comparison with the false-negative Group 1 (21.22 %; OR 1.48; 95 % CI, 1.16 to 1.89; P = 0.002). In comparison with the true-negative Group 4, univariate analyses showed significantly higher rates for sCS in all other groups: odds ratio (OR) 2.06 for Group 2 (95 % CI, 1.74 to 2.42; P < 0.001), 1.85 for Group 3 (95 % CI, 1.54 to 2.22, P < 0.001), and 1.25 for Group 1 (95 % CI, 1.05 to 1.49; P < 0.01). No significant differences were found for NO between Groups 1 and 3 for the parameters 5-min Apgar < 7 (P = 0.75), pH < 7.1 (P = 0.28), or NICU admission (P = 0.54). However, there was a significantly higher chance for shoulder dystocia in Group 1 compared with Group 3 (OR 4.58; 95 % CI, 1.34 to 24.30; P = 0.008)., Conclusion:  Sonographic EFW inaccuracies in fetal macrosomia appear to have a greater impact on the mode of delivery than birth weight itself. Underestimation of fetal weight may be associated with a higher probability of shoulder dystocia., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

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/m 2 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/m 2 were a particularly vulnerable group in the case of COVID-19., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction International studies on preterm birth rates during COVID-19 lockdowns report different results. This study examines preterm birth rates during lockdown periods and the impact of the mobility changes of the population in Bavaria, Germany. Material and Methods This is a secondary analysis of centrally collected data on preterm births in Bavaria from 2010 to 2020. Preterm births (< 37 weeks) in singleton and twin pregnancies during two lockdowns were compared with corresponding periods in 2010 - 2019. Fisher's exact test was used to compare raw prevalence between groups. Potential effects of two fixed lockdown periods and of variable changes in population mobility on preterm birth rates in 2020 were examined using additive logistic regression models, adjusting for long-term and seasonal trends. Results Unadjusted preterm birth rates in 2020 were significantly lower for singleton pregnancies during the two lockdown periods (Lockdown 1: 5.71% vs. 6.41%; OR 0.88; p < 0.001; Lockdown 2: 5.71% vs. 6.60%; OR = 0.86; p < 0.001). However, these effects could not be confirmed after adjusting for long-term trends (Lockdown 1: adj. OR = 0.99; p = 0.73; Lockdown 2: adj. OR = 0.96; p = 0.24). For twin pregnancies, differences during lockdown were less marked (Lockdown 1: 52.99% vs. 56.26%; OR = 0.88; p = 0.15; Lockdown 2: 58.06% vs. 58.91%; OR = 0.97; p = 0.70). Reduced population mobility had no significant impact on preterm birth rates in singleton pregnancies (p = 0.14) but did have an impact on twin pregnancies (p = 0.02). Conclusions Reduced preterm birth rates during both lockdown periods in 2020 were observed for singleton and twin pregnancies. However, these effects are reduced when adjusting for long-term and seasonal trends. Reduced population mobility was associated with lower preterm birth rates in twin pregnancies., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background/aim: We investigated the impact of the timing of antenatal corticosteroid (ACS) administration on the clinical outcome of preterm infants., Patients and Methods: Two hundred and fifty-five preterm infants between 28+0 and 34+0 weeks of gestation were retrospectively assigned to one of two groups: In the first group, ACS was given within 7 days before birth; the second group, did not receive ACS during that period. The primary outcome parameter was respiratory failure (defined by need for continuous positive airway pressure or mechanical ventilation) due to grade 1-4 respiratory distress syndrome (RDS). Secondary outcomes included the rates of intraventricular hemorrhage (IVH), periventricular leukomalacia, and necrotizing enterocolitis., Results: The rate of RDS was significantly higher in the no ACS group (40% vs. 62%, p=0.0009), especially of the more severe grades 24 (n=37 vs. n=48, p=0.0121). In addition, IVH (1% vs. 9%, p=0.0041) and neonatal infections (72% vs. 89%, p=0.0025) were significantly increased. Univariable and multivariable regression analyses showed a lower likelihood of RDS in the ACS group [odds ratio (OR)=0.295] in infants born closer to term (OR=0.907) and following preterm onset of labor (OR=0.495). Similarly, we observed a lower probability of IVH in the ACS group (OR=0.098), with a higher probability of occurrence of IVH in pre-eclampsia/HELLP syndrome (hemolysis, elevated liver enzyme levels, low platelet count) (OR=7.914)., Conclusion: ACS treatment within the last 7 days before birth significantly reduced the risk of RDS and IVH in preterm. These data emphasize that the timing of ACS administration determines its success., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose:  Introduction of a novel ratio - the amniotic-umbilical-to-cerebral ratio (AUCR) - to predict adverse perinatal outcome in SGA fetuses at term and comparison of its predictive accuracy with established parameters., Materials and Methods:  This retrospective cohort study included 165 singleton pregnancies with SGA fetuses (birth weight < 10 th percentile) at term. Cases with planned vaginal delivery and documented pulsatility indices (PI) of the umbilical artery (UA), middle cerebral artery (MCA), and single deepest pocket (SDP) were included. CPR was calculated as the ratio between MCA PI and UA PI, UCR as the ratio between UA PI and MCA PI. AUCR was defined as follows: SDP/(UA PI/MCA PI). Adverse perinatal outcomes were defined as operative intervention (OI), OI due to fetal distress, admission to the neonatal intensive care unit (NICU), and composite adverse perinatal outcome (CAPO). Associations between Doppler parameters and these outcomes were estimated using regression analyses., Results:  OI was statistically significantly associated with UCR, SDP, and AUCR, whereas no association was observed for UA PI, MCA PI, and CPR. Fetuses requiring OI due to fetal distress revealed a significantly higher UA PI and UCR as well as a lower MCA PI, CPR, and AUCR. With regard to NICU admission and CAPO, a significantly higher UA PI and lower CPR were found. Furthermore, a significant association was shown for SDP, UCR, and AUCR. AUCR achieved the best area under the curve for all outcome parameters., Conclusion:  AUCR leads to an improvement in the prediction of unfavorable outcome in SGA fetuses at term. Furthermore, results of our study show that UCR might be superior to CPR., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Purpose Detection of SARS-CoV-2-infected pregnant women admitted to maternity units during a pandemic is crucial. In addition to the fact that pregnancy is a risk factor for severe COVID-19 and that medical surveillance has to be adjusted in infected women and their offspring, knowledge about infection status can provide the opportunity to protect other patients and healthcare workers against virus transmission. The aim of this prospective observational study was to determine the prevalence of SARS-CoV-2 infection among pregnant women in the hospital setting. Material and Methods All eligible pregnant women admitted to the nine participating hospitals in Franconia, Germany, from 2 June 2020 to 24 January 2021 were included. COVID-19-related symptoms, secondary diseases and pregnancy abnormalities were documented. SARS-CoV-2 RNA was detected by RT-PCR from nasopharyngeal swabs. The prevalence of acute SARS-CoV-2 infection was estimated by correcting the positive rate using the Rogan-Gladen method. The risk of infection for healthcare workers during delivery was estimated using a risk calculator. Results Of 2414 recruited pregnant women, six were newly diagnosed RT-PCR positive for SARS-CoV-2, which yielded a prevalence of SARS-CoV-2 infection of 0.26% (95% CI, 0.10 - 0.57%). Combining active room ventilation and wearing FFP2 masks showed an estimated reduction of risk of infection for healthcare workers in the delivery room to < 1%. Conclusions The prevalence of newly diagnosed SARS-CoV-2 infection during pregnancy in this study is low. Nevertheless, a systematic screening in maternity units during pandemic situations is important to adjust hygienic and medical management. An adequate hygienic setting can minimise the calculated infection risk for medical healthcare workers during patients' labour., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objectives: To assess the frequency of antenatal corticosteroid (ACS) administration in cases with shortened cervical length by addition of placental alpha-microglobulin-1 (PAMG-1) testing to sonographic examination., Methods: Single centre retrospective cohort study. Rate of ACS administration was compared between cases with cervical length between 15 and 25 mm and cases with positive PAMG-1 testing and cervical length between 15 and 25 mm. We evaluated the following outcome parameters: Rate of ACS administration, gestational age at delivery, time to delivery, delivery within seven days, delivery <34 and <37 weeks' gestation, rate of admission to neonatal intensive care unit (NICU)., Results: In total, 130 cases were included. "PAMG-1 group" consisted of 68 women, 62 cases built the "historical control group". ACS administration was performed less frequently in the "PAMG-1 cohort" (18 (26%) vs. 46 (74%); p<0.001). The rate of delivery within seven days did not differ (2 (3%) vs. 4 (6.5%); p=0.4239). The rates of delivery <34 weeks' gestation (7 (10%) vs. 9 (15%); p=0.4643) and <37 weeks' gestation (19 (28%) vs. 26 (42%); p=0.0939) did not differ. Time to delivery interval was longer in the PAMG-1 group (61.5 vs. 43 days, p=0.0117). NICU admission occurred more often in the "historical control group" (22 (38%) vs. 28 (60%); p=0.0272)., Conclusions: Addition of biomarker testing can help to avoid unnecessary ACS administrations in women with shortened cervical length., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Purpose:  To evaluate the longitudinal pattern of fetal heart rate short term variation (STV) and Doppler indices and their correlation to each other in severe growth restricted (IUGR) fetuses., Materials and Methods:  In this retrospective study, pregnancies with a birth weight below the 10th percentile, born between 24 and 34 gestational weeks with serial Doppler measurements in combination with a computerized CTG (cCTG) with calculated STV were included. Longitudinal changes of both Doppler indices and STV values were evaluated with generalized additive models, adjusted for gestational age and the individual. For all measurements the frequency of abnormal values with regard to the time interval before delivery and Pearson correlations between Doppler indices and STV values were calculated., Results:  41 fetuses with a total of 1413 observations were included. Over the course of the whole study period, regression analyses showed no significant change of STV values (p = 0.38). Only on the day of delivery, a prominent decrease was observed (mean STV d28-22: 7.97 vs. mean STV on day 0: 6.8). Doppler indices of UA and MCA showed a continuous, significant deterioration starting about three weeks prior to delivery (p = 0.007; UA and p < 0.001, MCA). Correlation between any Doppler index and STV values was poor., Conclusion:  Fetal heart rate STV does not deteriorate continuously. Therefore, cCTG monitoring should be performed at least daily in these high-risk fetuses. Doppler indices of umbilical artery (UA) and middle cerebral artery (MCA), however, showed continuous deterioration starting about 3 weeks prior to delivery., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

In December 2019, cases of pneumonia of unknown cause first started to appear in Wuhan in China; subsequently, a new coronavirus was soon identified as the cause of the illness, now known as Coronavirus Disease 2019 (COVID-19). Since then, infections have been confirmed worldwide in numerous countries, with the number of cases steadily rising. The aim of the present review is to provide an overview of the new severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) and, in particular, to deduce from it potential risks and complications for pregnant patients. For this purpose, the available literature on cases of infection in pregnancy during the SARS epidemic of 2002/2003, the MERS (Middle East respiratory syndrome) epidemic ongoing since 2012, as well as recent publications on cases infected with SARS-CoV-2 in pregnancy are reviewed and reported. Based on the literature available at the moment, it can be assumed that the clinical course of COVID-19 disease may be complicated by pregnancy which could be associated with a higher mortality rate. It may also be assumed at the moment that transmission from mother to child in utero is unlikely. Breastfeeding is possible once infection has been excluded or the disease declared cured., Competing Interests: Conflict of Interest/Interessenkonflikt The authors declare that they have no conflict of interest./Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Objectives: To evaluate different formulas for estimating fetal weight in diabetic pregnancies., Methods: This retrospective study evaluated the precision of ultrasound fetal weight estimation in 756 pregnancies complicated by gestational diabetes between 2002 and 2016. The estimated fetal weights (EFWs) were obtained within 7 days of delivery from 10 weight estimation formulas and were compared with pair-wise matched controls from 15,701 patients. The precision of the evaluated formulas for EFW was analyzed by median absolute percentage errors (MAPEs), mean percentage errors (MPEs), and proportions of estimates within 10% of actual birth weight., Results: Among the tested formulas, the lowest MAPE was detected with formula I of Hadlock et al (Am J Obstet Gynecol 1985; 151:333-337), and the formula of Schild et al (Ultrasound Obstet Gynecol 2004; 23:30-35) had the highest proportion of estimates within the 10% range. The EFW in diabetic patients showed a slight trend toward overestimation in comparison with the matched controls (MPE estimates showed a trend toward more positive values). In most of the EFW formulas that were evaluated, no significant differences were detected in MAPEs and estimates within the 10% range. The MPE estimates with most formulas in both groups were close to zero. Overall, the differences between most of the evaluated formulas were small., Conclusions: Little evidence was found for differences in the accuracy of the EFW in diabetic pregnancies and controls. The Hadlock I formula showed the lowest MAPE, and the Schild formula had the highest proportion of estimates within the 10% range., (© 2019 by the American Institute of Ultrasound in Medicine.)

Single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor receptor 2 (VEGFR2) are associated with coronary artery disease, hypertension and myocardial infarction. However, their association with atherosclerosis remains to be fully elucidated. The purpose of the present study was to determine whether SNPs are involved in atherogenesis, by analyzing their impact on human umbilical vein endothelial cells (HUVECs) under laminar and non‑uniform shear stress in a well‑established in vitro model that simulates shear stress‑induced proatherogenic processes at vessel bifurcations. All experiments were performed using freshly isolated HUVECs. Three SNPs in the VEGFR2 gene (rs1870377 T>A, rs2071559 A>G and rs2305948 C>T) were genotyped and the expression levels of VEGFR2 were semi‑quantitatively determined using western blotting. Subsequently, the HUVECs were seeded in bifurcating flow‑through cell culture slides and flow (9.6 ml/min) was applied for 19 h, including tumor necrosis factor‑α stimulation during the final 2 h of flow. The protein expression levels of VCAM‑1, E‑selectin and VEGFR2 and the adhesion of THP‑1 cells were analyzed in laminar and non‑uniform shear stress regions. Data were analyzed for associations with the respective SNPs. The total expression of VEGFR2 was significantly lower under non‑uniform shear stress than under laminar shear stress conditions, independent of the genotype. The expression of VEGFR2 between the different shear stress patterns was not significantly altered by the different SNPs. The expression levels of VCAM‑1 and E‑selectin were lower in the A/A genotype compared with those in other genotypes in rs1870377 T>A and rs2071559 A>G. In conclusion, the results suggested that SNPs within the VEGFR2 gene have a significant impact on shear stress‑related endothelial activation.

Objective: To evaluate the association of short-term variation (STV) and Doppler parameters with adverse perinatal outcome in small-for-gestational-age (SGA) fetuses at term., Methods: In this retrospective single-center study 97 patients with singleton SGA fetuses at term (≥ 37 + 0 weeks' gestation) were examined. Inclusion criteria were a birth weight < 10th centile, cephalic presentation and planned vaginal birth. Only cases with available Doppler measurements of umbilical artery (UA) and middle cerebral artery (MCA) with calculated cerebroplacental ratio (CPR) in combination with a computerized CTG (cCTG) and STV 72 h prior to delivery were eligible for analysis. Pulsatility indices (PI) were converted into multiples of median (MoM), adjusted for gestational age. The association between Doppler indices and STV values with mode of delivery [secondary cesarean delivery (CD), operative vaginal delivery (OVD), as well as secondary CD and OVD due to fetal distress] and neonatal outcome [UA blood pH ≤ 7.15 and the need of admission to the neonatal intensive care unit (NICU)] was analyzed using logistic regression analysis., Results: There was a significant association between UA PI MoM and the rate of CD. CD due to fetal distress, OVD and OVD due to fetal distress did not show a correlation with the evaluated Doppler parameters. Furthermore, we did not find an association between low UA birth pH and Doppler parameters while neonates with the need of admission to NICU had significant higher UA PI MoM and significant lower MCA PI MoM and CPR MoM. Regarding STV, a significant effect of low STV on NICU admission was found while none of the other assessed outcome parameters were significantly associated with STV., Conclusion: STV and Doppler parameters in SGA fetuses at term are significantly associated to the rate of NICU admission.

A type 1 immune response is involved in atherosclerosis progression, whereas the role of a type 2 polarization, especially with regard to an enhanced T helper (T h )2 cell differentiation, is still unclear. Helminths trigger type 2 immune responses, protecting the host from inflammatory disorders. We investigated whether an increased type 2 polarization by administration of Litomosoides sigmodontis adult worm extract (LsAg) affects atherosclerosis in apolipoprotein E-deficient (ApoE -/- ) mice. Injections of 50 µg LsAg, i.p. into ApoE -/- mice induced a type 2 immune response shown by increased frequencies of peritoneal eosinophils and alternatively activated macrophages. To analyze the effect of LsAg on atherosclerosis initiation, ApoE -/- mice received a high-fat diet for 12 wk and weekly injections of 50 µg LsAg from wk 5 to 12. Therapeutic effects on advanced atherosclerosis were analyzed in mice that were fed a high-fat diet for 12 wk followed by 12 wk of normal chow and weekly LsAg injections. Both preventive and therapeutic LsAg application significantly decreased plaque size. Therapeutic treatment even caused regression of plaque size and macrophage density in the aortic root and reduced T h 1-specific gene expression and intraplaque inflammation. In addition, plaque size after therapeutic treatment was inversely correlated with plaque-infiltrated alternatively activated macrophages. In vitro , LsAg treatment of HUVECs reduced intracellular levels of phosphorylated NF-κB-p65, IκB-α, and JNK1/2. In bifurcation flow-through slides, THP-1 cell adhesion to a HUVEC monolayer was decreased by LsAg in regions of nonuniform shear stress. Applying inhibitors of the respective kinases suggests JNK1/2 inhibition is involved in the suppressed cell adhesion. A switch to an enhanced type 2 immune response by LsAg exerts antiatherogenic effects on murine plaque development, indicating a protective role of a hampered type 1 polarization. In vitro , LsAg affects endothelial signaling pathways, among which JNK1/2 inhibition seems to be involved in the suppression of monocytic cell adhesion under proatherogenic shear stress.-Constanze, K., Tauchi, M., Furtmair, R., Urschel, K., Raaz-Schrauder, D., Neumann, A.-L., Frohberger, S. J., Hoerauf, A., Regus, S., Lang, W., Sagban, T. A., Stumpfe, F. M., Achenbach, S., Hübner, M. P., Dietel, B. Filarial extract of Litomosoides sigmodontis induces a type 2 immune response and attenuates plaque development in hyperlipidemic ApoE-knockout mice.

Objective:  To evaluate the association of sonographic fetal biometry (sonographic head circumference (soHC), sonographic abdominal circumference (soAC), estimated fetal weight (EFW)) with mode of delivery and adverse perinatal outcome., Methods:  Singleton pregnancies with a gestational age ≥ 37 weeks and an ultrasound examination with complete biometric parameters within 7 days before delivery were retrospectively included. The association between soHC, soAC, EFW and fetal (5-min Apgar < 7, pH < 7.1, neonatal intensive care unit (NICU) admission, shoulder dystocia (ShD)) and maternal (obstetric intervention (OI): caesarean or vaginal operative delivery, obstetric anal sphincter injury syndrome (OASIS), postpartum hemorrhage (pph)) adverse outcomes were analyzed using univariate and multivariate logistic regression analyses., Results:  12 396 women were included and 3479 (28.07 %) needed an OI. Multivariate analyses demonstrated significant contributions for the prediction of OI by soHC and soAC, whereas EFW did not reach significance. The highest OR was shown for soHC (1087, p < 0.001). ShD occurred in 73 (0.59 %) of the deliveries. Multivariate analyses showed that significant contributions for the prediction of ShD were provided only by soAC (OR 1460, p = 0.007). For the other maternal and neonatal adverse outcome parameters, no significant association with the biometric measurements could be demonstrated in the multivariate analyses. The overall detection rates for the prediction of adverse perinatal outcome by the different biometric parameters and EFW were poor., Conclusion:  Obstetric management decisions should not be based solely on measurements of biometric parameters or EFW., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To evaluate the association of short-term variation (STV) and Doppler parameters with adverse perinatal outcome in low-risk fetuses at term., Methods: This was a retrospective study of 1008 appropriate-for-gestational age (AGA) term fetuses. Doppler measurements [umbilical artery (UA), middle cerebral artery (MCA), and cerebroplacental ratio (CPR)] and computerized CTG (cCTG) with STV analysis were performed prior to active labor (≤ 4 cm cervical dilatation) within 72 h of delivery. The association between Doppler indices and STV values with adverse perinatal outcome was analyzed using univariate regression analysis., Results: No significant association between Doppler parameters and the need for secondary cesarean delivery (CD) or operative vaginal delivery (OVD) was shown. Regarding fetuses delivered by CD due to fetal distress, regression analyzes revealed significantly higher UA PI MoM. However, the differences in MCA PI MoM and CPR MoM were not statistically significant. Fetuses with the need for emergency CD showed significantly higher UA PI MoM, lower MCA PI MoM and lower CPR MoM. Neonates with a 5-min Apgar score < 7 had significantly lower MCA PI MoM and neonatal acidosis (UA pH ≤ 7.10) showed a significant association with UA PI MoM. None of the assessed outcome parameters were significantly associated to STV., Conclusion: Doppler indices assessed close to delivery in low-risk fetuses at term show a moderate association with adverse outcome parameters, whereas STV does not appear to predict poor perinatal outcome in this group of fetuses.