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Objectives: To assess the risk of complications in women undergoing termination of pregnancy (TOP) for fetal defects and to examine the impact of gestational age on the complication rate. Methods: This was a retrospective study of women with a singleton pregnancy undergoing TOP at the University Hospital of Tübingen, Germany, between 2018 and 2021. TOP was performed by experienced operators according to the national protocol; dilatation and curettage (D&C) or evacuation (D&E) was used in the first and early second trimesters and induction was used later in pregnancy. The following were considered to be significant procedure‐related complications: blood loss of more than 500 mL, uterine perforation, need for blood transfusion, allergic reaction, creation of a false passage (via falsa), systemic infection, readmission to hospital, any unplanned surgical procedure, such as repeat D&C/D&E or hysterectomy, and maternal death. Results: The search of the hospital database identified 416 pregnancies that met the study criteria. Median maternal and gestational age at termination were 34.1 years and 17.4 weeks, respectively. In the first, second and third trimesters, respectively, 84 (20.2%), 278 (66.8%) and 54 (13.0%) pregnancies were terminated, for which D&C or D&E was used in 80 (95.2%), 21 (7.6%) and 0 (0.0%) cases. Seventy‐seven (18.5%) women had at least one previous Cesarean section and 169 (40.6%) had at least one previous spontaneous delivery. Overall, 95 (22.8%) women had complications during or after TOP. A significantly higher complication rate was noted for terminations performed later in pregnancy. The median gestational age at termination was 16.6 weeks in women who did not experience complications and 20.7 weeks in those with complications (P < 0.001). The respective complication rates in the first, second and third trimesters were 6.0%, 27.0% and 27.8%. Conclusion: In women undergoing TOP for fetal defects, the risk of complications increases with advancing gestational age. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To estimate the chorionic villus sampling (CVS)-related risk of fetal loss in twin pregnancy after adjustment for chorionicity, nuchal translucency thickness (NT), intertwin discordance in crown-rump length (CRL), maternal demographic characteristics and serum pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (β-hCG).Methods: This was a multicenter study from eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. Data were obtained prospectively from women with twin pregnancy undergoing routine ultrasound examination at 11-13 weeks' gestation. Multivariable logistic regression analysis with backward stepwise elimination was used to examine whether CVS provided a significant independent contribution to the prediction of risk of fetal loss after adjusting for maternal and pregnancy characteristics, including maternal age, racial origin and weight, method of conception, smoking status, parity, chorionicity, intertwin discordance in CRL, fetal NT ≥ 95th percentile and free β-hCG and PAPP-A multiples of the median. Similarly, within the CVS group, multivariable logistic regression analysis was used to investigate the effect of the number of intrauterine needle insertions and size of the needle on the risk of fetal loss.Results: The study population of 8581 twin pregnancies undergoing ultrasound examination at 11-13 weeks' gestation included 316 dichorionic and 129 monochorionic twins that had CVS. First, in twin pregnancies undergoing CVS, compared to those not undergoing CVS, there was a 2-fold increased risk of fetal loss at < 24 weeks' gestation and of loss at any stage in pregnancy. Second, the factors providing a significant independent contribution to the prediction of miscarriage or fetal loss in twin pregnancy were increased maternal weight, black racial origin, monochorionicity, and more so monoamnionicity, large intertwin discordance in CRL and increased fetal NT, and, in the case of fetal loss at any stage, there was also a contribution from assisted conception and low serum PAPP-A. Third, after adjustment for maternal and pregnancy characteristics, CVS did not provide a significant contribution to the risk of fetal loss. Fourth, in twin pregnancies that had CVS, there was no significant contribution to fetal loss from the number of intrauterine needle insertions or needle size.Conclusion: The 2-fold increased risk of fetal loss following CVS in twin pregnancy can, to a great extent, be explained by maternal and pregnancy characteristics rather than the invasive procedure itself. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To examine the effectiveness of single and repeat sonographic cervical-length (CL) measurement in predicting preterm delivery in symptomatic women with a twin pregnancy.Methods: This was a retrospective study of women with a twin gestation who presented with painful and regular uterine contractions at 24 + 0 to 33 + 6 weeks' gestation at the perinatal unit of the University Hospital of Tübingen, Tübingen, Germany between 2012 and 2018. CL was measured on transvaginal ultrasound at the time of admission and a few days later after cessation of contractions. Treatment included administration of tocolytics (usually oral nifedipine), for no more than 48 h, and administration of steroids if CL was ≤ 25 mm. Patients were clustered into five groups according to the CL measurement obtained at first assessment: < 10.0 mm; between 10.0 and 14.9 mm; between 15.0 and 19.9 mm; between 20.0 and 24.9 mm; and ≥ 25.0 mm. For each group, we calculated the test performance of CL measurement for prediction of preterm delivery within the subsequent 7 days and before 34 weeks' gestation. Regression analysis was used to evaluate the test performance of the second CL measurement for predicting preterm delivery within 7 days after the second assessment.Results: The study population consisted of 257 twin pregnancies, of which 80.2% were dichorionic diamniotic. Median maternal and gestational ages at the time of admission were 32.0 years and 29.9 weeks' gestation, respectively. Preterm birth within 7 days of admission occurred in 23 (8.9%) pregnancies, and 82 (31.9%) patients delivered prior to 34 weeks' gestation. Median CL for the entire study population was 17.0 mm. Delivery within 7 days after the first assessment occurred in 29.0%, 10.6%, 4.2%, 6.3% and 0% of women with CL < 10.0 mm, 10.0-14.9 mm, 15.0-19.9 mm, 20.0-24.9 mm and ≥ 25.0 mm, respectively. There was a weak, but significant, association between the CL measurement at the time of admission and the time interval between admission and delivery (interval = 27.9 + 0.58 × CL; P = 0.003, r = 0.184). CL was measured again after a median time interval of 3 (interquartile range (IQR), 2-5) days in 248 cases. Median second CL measurement was 17.0 (IQR, 11.5-22.0) mm. Delivery occurred within the subsequent 7 days after the second measurement in 25/248 (10.1%) cases. Binary regression analysis indicated that the first (odds ratio (OR), 0.895; P = 0.003) and second (OR, 0.908; P = 0.002) CL measurements, but not the difference between the two measurements (OR, 0.961; P = 0.361), were associated significantly with delivery within 7 days after the second measurement. Receiver-operating-characteristics (ROC)-curve analysis for the prediction of delivery within 7 days after the second assessment did not show a significant difference between the predictive performance of the first (area under ROC curve (AUC), 0.676 (95% CI, 0.559-0.793)) and the second (AUC, 0.661 (95% CI, 0.531-0.790)) measurement.Conclusion: Sonographic measurement of CL can be helpful in predicting preterm delivery within 7 days of presentation in symptomatic women with a twin gestation; however, the test performance is relatively weak. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To examine ductus venosus (DV) flow in fetuses with and those without a cardiac defect and to evaluate different phases of DV flow in addition to the standard assessment of DV pulsatility index for veins (PIV) and the a-wave.Methods: This was a retrospective study of singleton pregnancies that underwent first-trimester ultrasound screening, which included DV flow assessment, at the University of Tübingen (between 2010 and 2017) or the University of Cologne (between 2013 and 2016). The study population comprised normal fetuses and fetuses with major cardiac defects at a ratio of 10:1. For each fetus, the following parameters of the DV waveform were evaluated: qualitative assessment of the a-wave, PIV measurement and ratios of flow velocities during the S-wave (S) or D-wave (D) and the a-wave (a) or v-wave (v). Reproducibility of DV-PIV and DV flow ratios was evaluated in 30 fetuses in which the DV flow was assessed twice.Results: Our study population included 480 anatomically normal fetuses and 48 with a cardiac defect. Median fetal nuchal translucency (NT) in the normal and in the affected group was 1.9 mm and 2.6 mm, respectively. In five (1.0%) of the normal and 18 (37.5%) of the affected cases, fetal NT thickness was above the 99th centile. In the normal group, the DV a-wave was reversed in 15 (3.1%) cases and the DV-PIV was above the 95th centile in 25 (5.2%). In the cases with cardiac defects, the a-wave was reversed and the DV-PIV measurement was above the 95th centile in 26 (54.2%). The reproducibility of measurement of the ratios of DV flow velocities was similar to that of the DV-PIV. Most cardiac defects were associated with an abnormal a/S or a/D ratio. If the cut-off for these two ratios was set at the 5th centile of the normal distribution, the detection rate of fetal cardiac anomalies would be 62.5%. This compares favorably with the DV-PIV, which detects 26 (54.2%) of the affected fetuses for the same threshold.Conclusion: In the first trimester, the a/S ratio has the potential to detect approximately 60% of congenital cardiac defects for a false-positive rate of 5%. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between chronic hypertension (CH) and a wide range of adverse pregnancy outcomes after adjustment for confounding factors in obstetric history and maternal characteristics.Methods: This was a prospective screening study for adverse pregnancy outcomes in women with singleton pregnancy attending their first routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation. Data on maternal characteristics, medical and obstetric history and pregnancy outcome were collected. Regression analysis was performed to examine the association between CH and adverse pregnancy outcomes, including late miscarriage, stillbirth, pre-eclampsia (PE), gestational diabetes mellitus (GDM), spontaneous and iatrogenic preterm birth (PTB), small-for-gestational-age (SGA) neonate, large-for-gestational-age (LGA) neonate and elective and emergency Cesarean section (CS).Results: The study population of 109 932 pregnancies included 1417 (1.3%) women with CH. After adjusting for potential confounding variables from maternal characteristics, medical and obstetric history, CH was associated with increased risk of stillbirth (odds ratio (OR), 2.38 (95% CI, 1.51-3.75)), PE (OR, 5.76 (95% CI, 4.93-6.73)), SGA (OR, 2.06 (95% CI, 1.79-2.39)), GDM (OR, 1.61 (95% CI, 1.27-2.05)), iatrogenic PTB < 37 weeks (OR, 3.73 (95% CI, 3.07-4.53)) and elective CS (OR, 1.79 (95% CI, 1.52-2.11)), decreased risk of LGA (OR, 0.65 (95% CI, 0.53-0.78)) and had no significant effect on late miscarriage, spontaneous PTB or emergency CS.Conclusion: CH should be combined with other maternal characteristics and medical and obstetric history when calculating an individualized adjusted risk for adverse pregnancy complications. CH increases the risk of stillbirth, PE, SGA, GDM, iatrogenic PTB and elective CS and reduces the risk for LGA. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To evaluate a soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio cut-off of 38 for the prediction of pre-eclampsia (PE) in routine assessment in singleton pregnancies at 30-37 weeks' gestation.Methods: This was a prospective observational study in women attending a third-trimester ultrasound scan at 30-37 weeks as part of routine pregnancy care. Serum sFlt-1 and PlGF were measured and their ratio was calculated. We estimated the detection rate (DR), false-positive rate (FPR), positive predictive value (PPV) and negative predictive value (NPV) of sFlt-1/PlGF ratio >38 for the prediction of delivery with PE at < 1, < 4 and ≥ 4 weeks after assessment.Results: The study population of 12 305 singleton pregnancies was examined at a median of 32.4 (range, 30.0-36.9) weeks and included 14 (0.11%), 77 (0.63%) and 227 (1.84%) cases that subsequently delivered with PE at < 1, < 4 or ≥ 4 weeks' after assessment, respectively. The DR, FPR, PPV and NPV of sFlt-1/PlGF ratio > 38 in the prediction of delivery with PE at < 1 week were 78.6%, 4.5%, 1.9% and 99.97%, respectively; the values for delivery with PE at < 4 weeks were 76.6%, 4.1%, 10.4% and 99.85% and for delivery with PE ≥ 4 weeks were 20.7%, 4.3%, 8.3% and 98.47%.Conclusion: In routine screening of singleton pregnancies, the performance of a sFlt-1/PlGF ratio > 38 is modest for the prediction of delivery with PE at < 1 and at < 4 weeks after assessment and poor for the prediction of delivery with PE at ≥ 4 weeks after assessment. A sFlt-1/PlGF ratio > 38 predicted 79% of cases delivering with PE at < 1 week after assessment, at a FPR of 4.5%; consequently, a policy of hospitalizing patients with a ratio > 38 would potentially lead to unnecessary hospitalization in 4.5% of pregnancies and a ratio of ≤ 38 would falsely reassure one fifth of women who will deliver with PE within 1 week of assessment. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of the presence or absence of fetal anomalies and soft markers diagnosed by ultrasound on positive predictive value (PPV) 21, 18 and 13 in pregnancies with a high-risk cfDNA result., Methods: Retrospective study including singleton pregnancies with high-risk NIPT results for common trisomies followed by invasive testing. The cases were grouped by gestational age at the time of invasive testing and by the presence or absence of fetal abnormalities or soft markers. The ultrasound was considered abnormal if at least one major defect or a soft marker was detected., Results: A total of 173 women were included. Median maternal and gestational age was 37.7 years and 14.0 weeks, respectively. CfDNA test result showed high-risk for trisomy 21 and trisomy 18 or 13 in 119 and 54 cases, respectively. The "pre-ultrasound" PPV for trisomy 21 and for trisomy 18 or 13 were 98.3% and 68.4%, respectively. In case of a high-risk result for trisomy 21 and no fetal anomalies, the PPV was 86.7% while it was 100% if there were anomalies or markers present. In the case of a high-risk result for trisomy 18 or 13, the PPV was 9.5% if the ultrasound examination was normal and 100% if the ultrasound examination was abnormal., Conclusion: This study suggests that a detailed ultrasound examination performed after a cfDNA result that is high-risk for one of the common autosomal trisomies adds significantly to establishing an individualized risk assessment. This is particularly true in cases with a high-risk result for trisomies 18 or 13., (© 2023. The Author(s).)

In highly competitive contexts, deceptive intentions might be transparent, so conveying only false information to the opponent can become a predictable strategy. In such situations, alternating between truths and lies (second-order lying behavior) represents a less foreseeable option. The current study investigated the development of 8- to 10-year-old children's elementary second-order deception in relation to their attribution of ignorance (first- and second-order ignorance) and executive functions (inhibitory control, shifting ability, and verbal working memory). An adapted version of the hide-and-seek paradigm was used to assess children's second-order lie-telling, in which children were asked to hide a coin in either of their hands. Unlike the standard paradigm, the opponent did not consistently look for the coin in the location indicated by the children, so children needed to switch between telling simple lies and truths (elementary second-order lies about the coin location) to successfully deceive the recipient. The results showed that older children were less likely to tell elementary second-order lies. However, across the sample, when children decided to lie, this ability was positively related to their second-order ignorance attribution and their verbal working memory. Moreover, we obtained preliminary evidence for the presence of a habituation effect in second-order lying, with children being more accurate and having less variability in their truthful-to-deceive responses (this being the more frequently elicited response) than when telling lies to deceive. Our findings could have implications for understanding the mechanisms underlying children's ability to alternate between truths and lies to deceive., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing for limited resources with peers is common among children from an early age, illustrating their propensity to use deceptive strategies to win. We focused on how primary school-age (6-8 years old) children's strategic deception toward peers is associated with their socio-cognitive development (theory of mind and executive functions). In a novel computerized competitive hide-and-seek game, we manipulated the peer opponents' familiarity (familiar vs. unfamiliar) and actions (following vs. not following children's indications), as well as the stimuli likability (liked vs. disliked cards). Our findings demonstrated that children deceived the familiar opponent less than the unfamiliar one, indicating their determination to preserve positive peer interactions. We showed that theory of mind and executive functions significantly predicted children's willingness to deceive. Notably, second-order false belief understanding and visuospatial working memory positively predicted children's use of truths to deceive, whereas inhibitory control and cognitive flexibility efficacy scores were negatively related to their deceptive performance when using the same strategy. Implications for children's competitive behavior toward peers involving lie-telling are discussed., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

A systematic evaluation of the fetal anatomy as part of the second trimester ultrasound examination in pregnancy is useful in detecting pregnancy complications, fetal abnormalities, and genetic diseases. We aim to illustrate the basic and detailed second trimester scan, according to current international and national guidelines, as well as to our own every-day practice in the Department for Prenatal Diagnosis at the University of Tübingen, Germany., (© 2022. The Author(s).)

Background: Fetal akinesia (FA) results in variable clinical presentations and has been associated with more than 166 different disease loci. However, the underlying molecular cause remains unclear in many individuals. We aimed to further define the set of genes involved., Methods: We performed in-depth clinical characterisation and exome sequencing on a cohort of 23 FA index cases sharing arthrogryposis as a common feature., Results: We identified likely pathogenic or pathogenic variants in 12 different established disease genes explaining the disease phenotype in 13 index cases and report 12 novel variants. In the unsolved families, a search for recessive-type variants affecting the same gene was performed; and in five affected fetuses of two unrelated families, a homozygous loss-of-function variant in the kinesin family member 21A gene ( KIF21A ) was found., Conclusion: Our study underlines the broad locus heterogeneity of FA with well-established and atypical genotype-phenotype associations. We describe KIF21A as a new factor implicated in the pathogenesis of severe neurogenic FA sequence with arthrogryposis of multiple joints, pulmonary hypoplasia and facial dysmorphisms. This hypothesis is further corroborated by a recent report on overlapping phenotypes observed in Kif21a null piglets., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Dishonesty is an interpersonal process that relies on sophisticated socio-cognitive mechanisms embedded in a complex network of individual and contextual factors. The present study examined parental rearing practices, bilingualism, socioeconomic status, and children's interpretive diversity understanding (i.e., the ability to understand the constructive nature of the human mind) in relation to their cheating and lie-telling behavior. 196 school-age children (9-11 years old) participated in a novel trivia game-like temptation resistance paradigm to elicit dishonesty and to verify their interpretive diversity understanding. Results revealed that children's decision to cheat and lie was positively associated with their understanding of the constructive nature of the human mind and with parental rejection. Children with rejective parents were more likely to lie compared to their counterparts. This may suggest that understanding social interactions and the relationship with caregivers can impact children's cheating behavior and the extent to which they are willing to deceive about it. Understanding the constructive nature of the mind was also a positive predictor of children's ability to maintain their lies. Finally, being bilingual and having a higher socioeconomic status positively predicted children's deception, these intriguing results warranting further research into the complex network of deception influences.

Currently, there are no treatments that ameliorate cardiac cell death, the underlying basis of cardiovascular disease. An unexplored cell type in cardiac regeneration is cardiac Purkinje cells; specialized cells from the cardiac conduction system (CCS) responsible for propagating electrical signals. Purkinje cells have tremendous potential as a regenerative treatment because they may intrinsically integrate with the CCS of a recipient myocardium, resulting in more efficient electrical conduction in diseased hearts. This study is the first to demonstrate an effective protocol for the direct reprogramming of human cardiomyocytes into cardiac Purkinje-like cells using small molecules. The cells generated were genetically and functionally similar to native cardiac Purkinje cells, where expression of key cardiac Purkinje genes such as CNTN2, ETV1, PCP4, IRX3, SCN5a, HCN2 and the conduction of electrical signals with increased velocity was observed. This study may help to advance the quest to finding an optimized cell therapy for heart regeneration., Competing Interests: The authors declare that the following patent applications have been filed related to this work:•McConnell BK, Schwartz RJ, and Prodan N. Direct reprogramming of cells into cardiac Purkinje-like cells using a universal small molecule cocktail. US Provisional Patent Application Number: 63234399 - Filed Aug. 18, 2021.•McConnell BK, Schwartz RJ, and Prodan N. Direct reprogramming of cells into cardiac Purkinje-like cells using a universal small molecule cocktail. PCT Patent Application Number: PCT/US2022/039546 - Filed Aug. 5, 2022., (© 2022 The Author(s).)

Objective: To estimate the risk of fetal loss associated with chorionic villus sampling (CVS) in twin pregnancy, using propensity score analysis., Methods: This was a multicenter cohort study of women with twin pregnancy undergoing ultrasound examination at 11-13 weeks' gestation, performed in eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. The risk of death of at least one fetus was compared between pregnancies that had and those that did not have CVS, after propensity score matching (1:1 ratio). This procedure created two comparable groups by balancing the maternal and pregnancy characteristics that lead to CVS being performed, similar to how randomization operates in a randomized clinical trial., Results: The study population of 8581 twin pregnancies included 445 that had CVS. Death of one or two fetuses at any stage during pregnancy occurred in 11.5% (51/445) of pregnancies in the CVS group and in 6.3% (515/8136) in the non-CVS group (P < 0.001). The propensity score algorithm matched 258 cases that had CVS with 258 non-CVS cases; there was at least one fetal loss in 29 (11.2%) cases in the CVS group and in 35 (13.6%) cases in the matched non-CVS group (odds ratio (OR), 0.81; 95% CI, 0.48-1.35; P = 0.415). However, there was a significant interaction between the risk of fetal loss after CVS and the background risk of fetal loss; when the background risk was higher, the risk of fetal loss after CVS decreased (OR, 0.46; 95% CI, 0.23-0.90), while, in pregnancies with a lower background risk of fetal loss, the risk of fetal loss after CVS increased (OR, 2.45; 95% CI, 0.95-7.13). The effects were statistically significantly different (P-value of the interaction = 0.005). For a pregnancy in which the background risk of fetal loss was about 6% (the same as in our non-CVS population), there was no change in the risk of fetal loss after CVS, but, when the background risk was more than 6%, the posterior risk was paradoxically reduced, and when the background risk was less than 6%, the posterior risk increased exponentially; for example, if the background risk of fetal loss was 2.0%, the relative risk was 2.8 and the posterior risk was 5.6%., Conclusion: In twin pregnancy, after accounting for the risk factors that lead to both CVS and spontaneous fetal loss and confining the analysis to pregnancies at lower prior risk, CVS seems to increase the risk of fetal loss by about 3.5% above the patient's background risk. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Purpose: To examine if the uterocervical angle (UCA) can be used to predict preterm delivery in women with painful and regular uterine contractions and a cervical length of 25 mm or less., Methods: Retrospective study at the perinatal unit of the University Hospital of Tuebingen, Germany. Women with singleton gestation and preterm contractions between 24 + 0 and 33 + 6 weeks' gestation were included. For the UCA measurement, a line is placed from the internal os to the external os irrespective of whether the cervix is straight or curved. A second line is drawn to delineate the lower uterine segment. The angle between the two lines is the UCA measurement. The measurements were taken on stored images from our database., Results: The study consisted of 213 singleton pregnancies. At the time of UCA measurement, median maternal and gestational age was 31.4 years and 29.7 weeks' gestation. Median gestational age at delivery was 35.3 weeks and the corresponding birth weight 2480 g, respectively. The UCA measurement in women who delivered within 2 days, between 3-7 days and after 7 days was not helpful to distinguish between these three groups [median UCA measurements: 108.5°, 108.0° and 107.3° (Kruskal-Wallis test p = 0.576)]. Uni- and multivariate logistic multiple regression analysis demonstrated that the delivery within 2 days was only dependent on the gestational age and the cervical length at the time of presentation., Conclusion: The measurement of UCA is not useful in predicting preterm birth in the subsequent 7 days after an episode of preterm contractions., (© 2021. The Author(s).)

Objectives: The aim of this study was to explore elderly patients' beliefs about medicines in general, and specific towards their treatment and the relationship between beliefs and adherence., Methods: A cross-sectional study was performed by administering a questionnaire developed to meet the study's objectives. Elderly patients were recruited from three different settings., Results: 167 patients agreed to participate to our study, having a mean age of 73 years. Patients were aware of the necessity for treatment, but they also showed concern over the potential for the adverse outcomes. Only 15% of the patients were completely accepting their treatment having high necessity and low concerns, while 40% were ambivalent, having high necessity beliefs, but also high concerns, with 89% being adherent in this group. Overall, higher adherence was significantly correlated with higher necessity and with higher necessity-concern differential., Conclusion: Patients beliefs have an impact on adherence, thus patients' concerns and necessities should be addressed in order to improve adherence and treatment outcome., Practice Implications: Higher necessity positively influenced adherence to treatment, suggesting the fact that healthcare professionals could improve patients' adherence by outlining and educating the patients on the necessity of the treatment, while also managing patients' concerns., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To determine whether the frontomaxillary facial (FMF) angle and the prefrontal space ratio (PFSR) are helpful in screening for open spinal defects by ultrasound in the second and third trimesters of pregnancy., Methods: The FMF angle and the PFSR were measured in fetuses with spina bifida according to standardized protocols. The normal range of the PFSR was previously published by our group. To determine the normal values for the FMF angle in the second and third trimesters of pregnancy, we used the same stored images from the above-mentioned study., Results: 71 affected and 279 normal fetuses were included in this study. Median gestational ages in the two groups were 21.1 weeks and 21.6 weeks, respectively. In fetuses with spina bifida, the FMF angle was significantly smaller than in the normal population (72.9° versus 79.6°). However, the measurement was below the fifth centile in only 22.5% of the affected fetuses. The PFSR was similar in both groups., Conclusions: The FMF angle is smaller in second and third trimester fetuses with open spina bifida. However, the difference is not large enough to implement this marker in current screening programs.

Class B G protein-coupled receptors are highly therapeutically relevant but challenges remain in identifying suitable small-molecule drugs. The calcitonin-like receptor (CLR) in particular is linked to conditions such as migraine, cardiovascular disease, and inflammatory bowel disease. The CLR cannot act as a cell-surface receptor alone but rather must couple to one of three receptor activity-modifying proteins (RAMPs), forming heterodimeric receptors for the peptides adrenomedullin and calcitonin gene-related peptide. These peptides have extended binding sites across their receptors. This is one reason why there are few small-molecule ligands that can modulate these receptors. Here we describe small molecules that are able to positively modulate the signaling of the CLR with all three RAMPs but are not active at the related calcitonin receptor. These compounds were selected from a β-arrestin recruitment screen, coupled with rounds of medicinal chemistry to improve their activity. Translational potential is shown as the compounds can positively modulate cAMP signaling in a vascular cell line model. Binding experiments do not support an extracellular domain binding site; however, molecular modeling reveals potential allosteric binding sites in multiple receptor regions. These are the first small-molecule positive modulators described for the CLR:RAMP complexes., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Adrenomedullin (AM) is a 52 amino acid peptide that plays a regulatory role in the vasculature. Receptors for AM comprise the class B G protein-coupled receptor, the calcitonin-like receptor (CLR), in complex with one of three receptor activity-modifying proteins (RAMPs). The C-terminus of AM is involved in binding to the extracellular domain of the receptor, while the N-terminus is proposed to interact with the juxtamembranous portion of the receptor to activate signaling. There is currently limited information on the molecular determinants involved in AM signaling, thus we set out to define the importance of the AM N-terminus through five signaling pathways (cAMP production, ERK phosphorylation, CREB phosphorylation, Akt phosphorylation, and IP 1 production). We characterized the three CLR:RAMP complexes through the five pathways, finding that each had a distinct repertoire of intracellular signaling pathways that it is able to regulate. We then performed an alanine scan of AM from residues 15-31 and found that most residues could be substituted with only small effects on signaling, and that most substitutions affected signaling through all receptors and pathways in a similar manner. We identify F18, T20, L26, and I30 as being critical for AM function, while also identifying an analogue (AM 15-52 G19A) which has unique signaling properties relative to the unmodified AM. We interpret our findings in the context of new structural information, highlighting the complementary nature of structural biology and functional assays., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Objectives: The aims of the study were to assess the false-positive and uninformative test rate with first trimester cell-free DNA (cfDNA) screening for common trisomies and microdeletion 22q11.2 (22q11.2DS) and to examine women's attitudes toward such an approach., Methods: This is a prospective study at the Prenatal Medicine Department of the University of Tübingen, Germany, at 11-13 weeks. In all pregnancies, a detailed ultrasound examination was carried out, followed by a cfDNA analysis for common trisomies and 22q11.2DS. In cases where the cfDNA analysis indicated 22q11.2DS, invasive prenatal diagnostic testing and parental testing were performed. After delivery, a detailed neonatal clinical examination was carried out including further genetic testing. Prior to counselling about the study, we asked the pregnant women who were potentially eligible for the study to anonymously report on their knowledge about 22q11.2DS., Results: A total of 1,127 pregnancies were included in the final analysis of the study. The first cfDNA test was uninformative in 15 (1.33%) pregnancies. In 10 (0.89%) cases, the test remained uninformative, even after the second blood sample. There were 3 (0.27%) cases with a positive cfDNA test for 22q11.2DS. In all, 983 women returned the anonymous questionnaire prior to study participation. Only 80 (8.1%) women responded that they felt familiar or very familiar with 22q11.2DS., Conclusion: The addition of 22q11.2DS in first trimester cfDNA screening for common trisomies is feasible. The uninformative test rate for common trisomies and 22q11.2DS is 0.9%, and the false-positive rate for 22q11.2DS is 0.3%. Awareness and education around 22q11.2DS should be improved., (© 2020 S. Karger AG, Basel.)

Objective: To examine whether the uterine artery PI is different in aneuploid and euploid pregnancies., Methods: Retrospective case-matched study at the department of prenatal medicine at the University of Tuebingen, Germany. The study involved patients with complete data on first trimester screening for trisomies and preeclampsia except PlGF. For each case with trisomy 21 we randomly selected 50 cases with a euploid fetus where complete data on screening for aneuploidy and preeclampsia were also available. The uterine artery pulsatility index and the corresponding MoM values of euploid and the aneuploid population were compared with a Man-Whitney U test., Results: The dataset consisted of 4591 singleton pregnancies. The karyotype was normal in 4500 cases and was abnormal in the remaining 91 pregnancies. There were 50 pregnancies with trisomy 21, 31 with trisomy 18 and 13, and 10 with triploidy. In the group with euploid fetuses, median uterine artery PI was 1.55 (0.99 MoM). In the group with trisomy 21, the median PI (1.42) and MoM (0.89) levels were both significantly lower than in the euploid (p < 0.001). However, the measurements in the trisomy 18 and 13 [1.61 (0.93 MoM)] and in the triploidy [1.99 (1.13 MoM)] groups were not significantly different from those in the euploid group (p = 0.468 and p = 0.632, respectively)., Conclusion: In conclusion, uterine artery PI levels in the first trimester are slightly lower in pregnancies with trisomy 21. This knowledge may prove to be useful in cases where a low PAPP-A level is seen on the first trimester maternal serum biochemical evaluation to differentiate whether the more likely cause for this finding is placental dysfunction or aneuploidy, specifically trisomy 21.

Objective: To examine the blood flow in the splenic artery as marker for materno-fetal transmission at about 20 weeks following a maternal first-trimester primary CMV infection., Methods: This is a retrospective study at the prenatal medicine unit at University of Tuebingen, Germany. Women were included who underwent an amniocentesis to examine the fetal infection status following a maternal primary CMV infection in the first trimester. In all cases, amniocentesis was done at about 20 weeks and at least 6 weeks after the maternal infection. As part of the detailed ultrasound examination prior to each amniocentesis, we examined the peak systolic velocity flow (PSV) and the pulsatility index (PI) of the splenic artery. Measurements were transformed into MoMs according to the normal curves of Ebbing et al. RESULTS: 81 Women fulfilled the inclusion criteria. Maternal and gestational age was 31.9 years and 20.6 weeks' gestation. Maternal-fetal transmission occurred in 13 of the cases. In fetuses without and with a CMV infection, mean PI was 0.98 MoM and 0.89 (p = 0.081). Mean PSV was significantly higher in the group of infected fetuses than in those without (1.24 vs. 0.94 MoM, p = 0.026)., Conclusion: The PSV may be a marker for maternal-fetal CMV transmission following a first-trimester maternal infection.

Objective: To compare several strategies for second trimester labor induction for termination of pregnancy (TOP) using misoprostol and mifepristone and to determine which one is more effective in accelerating the time to delivery., Method: This was a retrospective study in which pregnancies that underwent second and third trimester TOP due to fetal anomalies between 2007 and 2017 were classified into a group that received misoprostol alone, a group that received mifepristone followed by misoprostol on the same day, one where misoprostol was given 1 day after mifepristone and one where the medications were administered 2 days apart. The primary outcome measure was the induction to delivery interval., Results: 481 pregnancies fulfilled the inclusion criteria. In 140 cases, mifepristone was not administered. 341 women received mifepristone prior to induction, which was administered on the day of induction in 85 cases, and 1 or 2 days prior to induction in 140 and 19 cases. Median time interval between first induction and delivery was 15.0 (IQR 10.0-24.1) h in case no mifepristone was given and 13.2 (9.7-18.2) h if mifepristone was given on the same day and 9.3 (6.6-14.9) and 10.5 (7.2-22.3) h, if mifepristone was given 1 or 2 days prior to induction. After 24 h, the proportion of terminated pregnancies in each of the four groups was 75.0, 83.5, 93.2 and 78.9%., Conclusion: A 1 day interval between mifepristone and misoprostol is more effective in second and third trimester TOP compared to other strategies in terms of reducing the induction to abortion interval.

Purpose: To determine the false-positive rates (FPR) associated with screening for trisomy 18/13 using first-trimester combined screening (FTCS) and an ultrasound plus cfDNA-based approach (US-cfDNA), which includes a detailed ultrasound examination, a cfDNA analysis and a FTCS reflex backup test for cases with uninformative results., Methods: This is a sub-analysis of a randomized controlled trial, which was performed between 2015 and 2016. Pregnant women with a normal first-trimester ultrasound examination at 11-13 weeks' gestation (NT < 3.5 mm, no anomalies) were randomized into two groups: FTCS and US-cfDNA screening. The overall FPR in screening for trisomies 18/13 and 21 was compared with the FPR in screening for trisomy 21 alone. Pregnancies were considered screen positive if the risk for trisomy 21 was 1:100 and for trisomy 18 and 13, 1:20 each., Results: The study population consisted of 688 pregnancies in each study arm. In the FCTS group, median delta NT was 0.0 mm, free beta-hCG and PAPP-A 0.96 and 1.11 MoM. In the US-cfDNA group, median delta NT was 0.0 mm. In 10 pregnancies, the cfDNA analysis was uninformative. In the FTCS and in the US-cfDNA group, the FPR in screening for trisomy 21 was 2.5% and 0%. In both groups, the overall FPR was not increased by adding screening algorithms for trisomies 18 and 13., Conclusion: In conclusion, the addition of screening for trisomies 18 and 13 to screening for trisomy 21 does not significantly change FPR. This is true for both the FTCS and the US-cfDNA-based approach.

Introduction This study investigates whether the time of diagnosis of foetal trisomy 21/18/13 and the frequency of termination of pregnancy have changed in the past 10 years. Material and Methods Retrospective study at the Tübingen University Centre for Women's Health in which the cases with ante- and postnatal diagnosis of trisomy were investigated. A prerequisite was that the patients be examined in the antenatal medicine department. The time of diagnosis, the frequency of termination of pregnancy and the gestational age in the case of a termination were assessed. Results Between 2007 and 2017, trisomy 21/18/13 was diagnosed in 498 foetuses and newborns. In 311 of the foetuses or newborns, trisomy 21 was identified; in 134, trisomy 18; and in 53, trisomy 13. The median gestational age at diagnosis in the case of foetuses with trisomy 21 was between 14.4 and 13.6 weeks of pregnancy. The rate of pregnancy terminations increased slightly from 66.7% between 2007 and 2010 to 75.5% between 2015 and 2017. The median gestational age at the time of termination remained constant at 14.9 and 15.0 weeks of pregnancy respectively. The median gestational age at diagnosis in the case of foetuses with trisomy 18/13 was between 13.6 and 14.6 weeks of pregnancy during the examination period. The percentages of affected pregnancies which were terminated in the three time periods increased slightly from 57.4 to 69.0%. The gestational age remained unchanged in this case at 15.0 and 15.1 weeks of pregnancy respectively. Conclusion The time of intrauterine diagnosis of trisomy 21/18/13 has not changed in the past 10 years. The frequency of termination of a pregnancy increased slightly and the time of termination remained unchanged.

Objective: To examine whether in fetuses with trisomy 21 (T21), the ductus venosus (DV) flow differs in presence of a major cardiac defect (congenital cardiac defect [CHD]) and whether this affects the risk distribution in first trimester screening for T21., Methods: This retrospective study included pregnant women who underwent first trimester screening. This involves an examination of the crown-rump length, the nuchal translucency, the ductus venosus (DV) flow, and the heart. Three groups of fetuses were examined: euploid without CHD, T21 with CHD, and T21 without CHD. We examined the DV pulsatility index for veins, the direction of the a-wave, and ratios of velocities: v/S, v/D, a/S, a/D, and S/D., Results: The study population consisted of 410 euploid fetuses and 136 with T21 (51 with CHD and 85 without CHD). In the 3 groups, the a-wave was reversed in 3.2%, 66.7%, and 57.6%. The DV flow ratios in T21 with and without CDH were significantly different compared with normal fetuses. When comparing the ratios between the 2 T21 groups, only the a/S and a/D ratio were significantly different. The risk distributions in screening for T21 with and without CDH were similar., Conclusion: There are some small differences in the DV flow of T21 fetuses with and without CHD, but they are not clinically useful., (© 2018 John Wiley & Sons, Ltd.)

Histological and histomorphometric examinations of rat adrenals after a 7-day flight revealed the following changes: blood congestion in the cortex and medulla, progressive delipoidization of the cortex, slight enlargement of the nuclear volume of glomerular and fascicular zones, vacuolization of the cytoplasm of medulla cells, reduction of the area of noradrenocyte islets and cell nuclei of the medulla; the adrenal weight remained however unchanged. It is concluded that an early period of adaptation to microgravity was accompanied by a weak stress-reaction. Upon return to Earth the rats developed an acute gravitational stress. From the morphological point of view the stress manifested as: increased volume of nuclei in fascicular cells, decreased content of lipids in them, and greater vacuolization of the cytoplasm of medulla cells. The lack of medulla hypertrophy, reduction of the area of noradrenocyte islets and nuclei of medulla cells suggest that 7-day exposure to microgravity did not exert of stimulating effect on the sympathetic system of rats.