Clinical Course and Outcome of Prenatally Detected 22q11.2 Deletion Syndrome-A Retrospective Analysis.

The 22q11.2 deletion syndrome (22q11.2 DS) is known as the most common microdeletion syndrome. Due to its variable clinical phenotype, prenatal diagnosis can be challenging. The aim of this retrospective study was to evaluate the clinical course and pregnancy outcome of cases with prenatally diagnosed 22q11.2 deletion syndrome (DS) as well as to evaluate the role of prenatal magnetic resonance imaging (MRI) and postmortem examination. In total, 21 cases who underwent prenatal ultrasound examination and pregnancy care at the Department of Obstetrics and Gynecology at the Medical University of Vienna between 2012 and 2022 were included. The majority of the cases were genetically diagnosed using fluorescent in situ hybridization (FISH). The median gestational age (GA) at genetic diagnosis was 23.0 weeks (IQR 21.4-24.8 weeks). CHDs were detected in all fetuses and the most common extracardiac manifestation was thymus hypo/aplasia followed by genitourinary anomalies. Prenatal magnetic resonance imaging (MRI) revealed additional diagnostic information in three of ten cases. Overall, 14 patients opted for drug-induced TOP, of which 9 cases had a feticide prior to the induction of labor. The majority of craniofacial malformations were only detected by autopsy. In conclusion, the majority of cases prenatally diagnosed with 22q11.2 DS had an absent or hypoplastic thymus noted antenatally in addition to the detected CHD, and almost half of the cases had another extracardiac malformation of predominantly genitourinary origin. Furthermore, prenatal MRIs confirmed previously detected malformations, but only provided additional diagnostic information in three out of ten cases, whereas postmortem examination diagnosed most of the craniofacial anomalies and should always be conducted, serving as an important quality indicator for prenatal imaging.

Fetal Growth Restriction Is Associated with Pregnancy Associated Plasma Protein A and Uterine Artery Doppler in First Trimester.

Fetal growth restriction (FGR) is a major cause of stillbirth and poor neurodevelopmental outcomes. The early prediction may be important to establish treatment options and improve neonatal outcomes. The aim of this study was to assess the association of parameters used in first-trimester screening, uterine artery Doppler pulsatility index and the development of FGR. In this retrospective cohort study, 1930 singleton pregnancies prenatally diagnosed with an estimated fetal weight under the third percentile were included. All women underwent first-trimester screening assessing maternal serum pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotrophin levels, fetal nuchal translucency and uterine artery Doppler pulsatility index (PI). We constructed a Receiver Operating Characteristics curve to calculate the sensitivity and specificity of early diagnosis of FGR. In pregnancies with FGR, PAPP-A was significantly lower, and uterine artery Doppler pulsatility index was significantly higher compared with the normal birth weight group (0.79 ± 0.38 vs. 1.15 ± 0.59, p < 0.001 and 1.82 ± 0.7 vs. 1.55 ± 0.47, p = 0.01). Multivariate logistic regression analyses demonstrated that PAPP-A levels and uterine artery Doppler pulsatility index were significantly associated with FGR (p = 0.009 and p = 0.01, respectively). To conclude, these two parameters can predict FGR < 3rd percentile.

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.

HPV screening in the urine of transpeople - A prevalence study.

Background: There is limited data on human papillomaviruses (HPV) prevalence in transpeople due to low acceptance rate of screening methods. HPV tests from self-collected urine are gender-neutral, have a high acceptance, and have a comparable accuracy in females to clinician-collected samples. The aim of this study was to evaluate both the HPV prevalence in the urine in a large cohort of 200 transpeople with common risk profiles and the acceptability of such screening method. Methods: The study was conducted at the outpatient clinic for transpeople at the Department of Obstetrics and Gynaecology, Medical University of Vienna, Austria. 200 transpeople have been enrolled between May and October 2021. Inclusion criteria were gender identity dysphoria, age over 18 years, and adequate language skills.Subjects were asked to answer a survey concerning gender identity, established risk factors for HPV infections as well as their preference regarding urine or provider-collected cytology-/HPV-based screening, and to provide a urine sample. Five patients not able to provide urine were excluded. HPV genotyping was performed using a validated multiplex real-time PCR assay, which simultaneously detects 28 HPV genotypes. This trial is registered at ClinicalTrials.gov, NCT04864951. Findings: Overall HPV positivity was 19·0% (37/195), 24·2% in female to male, 11·8% in male to female, 26·3% in genderqueer/non binary/other subjects, 27·9% in subjects currently having a cervix, and 26·0% in subjects born with cervix. Independent of gender reassignment surgery, being born with a cervix was associated with a higher risk of HPV infections (p = 0·008), yet 42·3% (44/104) have never attended cervical cancer screening. Overall, 79·0% (154/195) of transpeople would prefer urine HPV tests to provider-collected HPV screening. Interpretation: HPV testing in self-collected urine samples provides a unique opportunity for screening of this hard-to-reach population and should be evaluated in further studies. Funding: None.

Outcome after Prenatal Diagnosis of Trisomy 13, 18, and 21 in Fetuses with Congenital Heart Disease.

Fetal congenital heart disease (CHD) is often associated with chromosomal abnormalities. Our primary aim was to assess stillbirth and neonatal mortality rates for pregnancies complicated by trisomies 13, 18, and 21 in the presence of CHD, from a single tertiary referral center during 2000-2020 in a retrospective cohort study. The secondary aims were to investigate maternal morbidity in these pregnancies, and to study the gestational or neonatal age when mortality occurred. Inclusion criteria were the prenatal diagnosis of at least one structural CHD, together with prenatally diagnosed fetal trisomy 13, 18, or 21. One-hundred and sixty patients with fetal trisomy 13 (14.4%), fetal trisomy 18 (28.8%), and fetal trisomy 21 (56.9%) were evaluated. In total, 98 (61.3%) families opted for the termination of pregnancy (TOP). Of the remaining 62 (38.8%) pregnancies, 16 (25.8%) resulted in intrauterine fetal death/death during delivery. Ten out of twenty-one (47.6%) infants with trisomy 13 or 18 were born alive. The livebirth rate was 87.8% (36/41) for infants with trisomy 21. Early neonatal death was observed in nine (19.6%) infants. Thirty-one (86.1%) infants with trisomy 21 survived the first year of life. These data may be helpful for counseling affected parents when the decision to terminate or continue the pregnancy should be considered.

Neutrophil Gelatinase-Associated Lipocalin and Hypertensive Disorders of Pregnancy: A Cohort Study in Twin Pregnancies.

Hypertensive disorders complicate more than 10% of twin pregnancies. Several studies showed increased neutrophil gelatinase-associated lipocalin (NGAL) values in women with singleton pregnancies and preeclampsia. This study aimed to assess NGAL values in twin pregnancies complicated by hypertensive disorders. We conducted a study of 242 consecutive twin pregnancies at the Medical University of Vienna. Serum NGAL was evaluated twice during pregnancy and once in the postpartum period. Furthermore, serum NGAL values were compared between women who developed hypertensive disorders and those who had normal blood pressure. In all twin pregnancies, mean NGAL values increased significantly from the first to the second visit (p = 0.004) and, further, after delivery (p < 0.001). NGAL was significantly higher in pregnancies that developed pregnancy hypertension or preeclampsia when compared to the control group at the first visit (109.2 ± 48.9 ng/mL vs. 91.9 ± 29.4 ng/mL, p = 0.04, respectively). The predictive power of first visit NGAL values for development of pregnancy hypertension or preeclampsia was evaluated. When using a cut-off value of 115 ng/mL, we obtained a sensitivity of 45% with a specificity of 77%. We conclude that women with twin pregnancies who develop hypertensive disorders of pregnancy showed increased NGAL values at 11−16 weeks.

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.

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.

Three or less? Decision making for or against selective reduction and psychological outcome in forty women with a triplet pregnancy.

OBJECTIVES: The aim of the study was to investigate decision making for or against multifetal pregnancy reduction (MFPR) and psychological outcome in women with a triplet pregnancy. METHODS: We investigated medical and sociodemographic variables and characteristics of the decision process for or against MFPR in forty women with triplet pregnancies who had either undergone MFPR (MFPR-group: N = 10) or had delivered triplets (triplet-group: N = 30). Moreover, emotional experiences of the reduction procedure were assessed. Psychological outcome was measured using the Beck Depression inventory (BDI) and the 36-Item Short Form Health Survey (SF-36). RESULTS: Women of the MFPR-group had a higher gestational age at delivery (p = 0.001), shorter NICU stay (p = 0.001), higher educational level (p = 0.010), more frequently utilized psychological counseling during the decision process (p = 0.016), rated their gynecologist as more helpful for the decision (p = 0.045), required more time for their decision (p = 0.016), and were more likely to be in paid employment at follow-up (p = 0.041) than women of the triplet-group. MFPR was experienced as stressful (90%) or terrifying (10%). At 3.2 (±2.2) years after delivery, the vast majority of women in both groups were free from clinically relevant depression. CONCLUSIONS: MFPR, though associated with emotional distress related to the procedure, results in a satisfactory psychological outcome in the majority of women. The decision for or against MFPR may be related to sociodemographic (such as educational) variables, which further supports the concept of framing in medical decision making. Having triplets most probably is associated with multiple (e.g. social or economic) consequences that may remain poorly investigated.

Notching and Pulsatility Index of the Uterine Arteries and Preeclampsia in Twin Pregnancies.

Increased uterine artery Doppler indices have been shown to be associated with preeclampsia and adverse pregnancy outcomes in singleton and twin pregnancies. At 20-22 weeks of gestation, we assessed the use of notching, the highest, lowest, and mean pulsatility index (PI), and the combination of notching and PI of the uterine arteries to screen for preeclampsia. This was done in a cohort of 380 twin pregnancies. The results showed that the combination of notching and the highest PI above the 95th centile of the uterine arteries gives the best screening characteristics for preeclampsia in twin pregnancies. We calculated sensitivities for preeclampsia for notching, highest PI, and the combination of notching and the highest PI of 50%, 45% and 91%, with specificities of 96%, 96% and 93%, respectively. The present findings demonstrate that notching, increased highest PI, and the combination of notching and the highest PI of the uterine arteries is associated with an increased risk of preeclampsia in twin pregnancies. We observed the highest sensitivity and specificity by using the combination of notching and the highest PI of the uterine arteries.

Vaginal Progesterone Has No Diabetogenic Potential in Twin Pregnancies: A Retrospective Case-Control Study on 1686 Pregnancies.

BACKGROUND: In this study, we aimed to investigate the incidence of gestational diabetes mellitus (GDM) in women who carried twin pregnancies and received vaginal progesterone. METHODS: In this retrospective cohort study, 203 out of 1686 women with twin pregnancies received natural progesterone (200 mg/day between gestational weeks 16 + 0 and 36 + 0) vaginally for ≥ 4 weeks. The control group consisted of 1483 women with twin pregnancies without progesterone administration. Pearson's Chi squared test, Fisher's exact test, and Student's t-test was used to compare differences between the control and the progesterone-treated groups. A multivariate binary logistic regression was performed to assess relative independent associations on the dependent outcome of GDM incidence. RESULTS: Vaginal progesterone treatment in twin pregnancies had no significant influence on developing GDM (p = 0.662). Higher pre-pregnancy BMI (OR 1.1; p < 0.001), GDM in previous pregnancy (OR 6.0; p < 0.001), and smoking during pregnancy (OR 1.6; p = 0.014) posed an increased risk for developing GDM. CONCLUSION: In twin pregnancies, the use of vaginal progesterone for the prevention of recurrent preterm delivery was not associated with an increased risk of GDM.

Prevalence of Gestational Diabetes in Triplet Pregnancies: A Retrospective Cohort Study and Meta-Analysis.

BACKGROUND: Over the last decades, there has been a substantial increase in the incidence of higher-order multiple gestations. Twin pregnancies are associated with an increased risk of gestational diabetes mellitus (GDM). The literature on GDM rates in triplet pregnancies is scarce. METHODS: A retrospective cohort study was performed to assess the prevalence of GDM in women with a triplet pregnancy. GDM was defined through an abnormal oral glucose tolerance test (OGTT). A meta-analysis of GDM prevalence was also carried out. RESULTS: A cohort of 60 women was included in the analysis. Of these, 19 (31.7%) were diagnosed with GDM. There were no differences in pregnancy outcomes between women with and without GDM. In the meta-analysis of 12 studies, which used a sound GDM definition, an estimated pooled prevalence of 12.4% (95% confidence interval: 6.9%-19.1%) was found. In a leave-one-out sensitivity analysis, the estimated GDM prevalence ranged from 10.7% to 14.1%. CONCLUSION: The rate of GDM seems increased in women with triplets compared to singleton pregnancies. However, GDM did not impact short-term pregnancy outcomes.

Effect of Viewing Disney Movies During Chemotherapy on Self-Reported Quality of Life Among Patients With Gynecologic Cancer: A Randomized Clinical Trial.

Importance: In addition to treatment efficacy, evaluation of adverse effects and quality of life assessments have become increasingly relevant in oncology. Objective: To evaluate the association of watching Disney movies during chemotherapy with emotional and social functioning and fatigue status. Design, Setting, and Participants: This randomized clinical trial was performed from December 2017 to December 2018 at a cancer referral center in Vienna, Austria. A consecutive sample of women with gynecologic cancers was recruited through July 2018. Inclusion criteria included age older than 18 years, written informed consent, and planned 6 cycles of chemotherapy with either carboplatin and paclitaxel or carboplatin and pegylated liposomal doxorubicin. Exclusion criteria were inadequate knowledge of the German language or receipt of other chemotherapy regimens. Data analysis was performed from February 2019 to April 2019. Intervention: Participants were either shown Disney movies or not during 6 cycles of chemotherapy. Before and after every cycle, they completed standardized questionnaires from the European Organisation for Research and Treatment of Cancer (EORTC). Main Outcomes and Measures: Primary outcomes were change of quality of life, as defined by the EORTC Core-30 (version 3) questionnaire, and fatigue, as defined by the EORTC Quality of Life Questionnaire Fatigue, during 6 cycles of chemotherapy. Results: Fifty-six women entered the study, and 50 completed it, including 25 women in the Disney group (mean [SD] age, 59 [12] years) and 25 women in the control group (mean [SD] age, 62 [8] years). In the course of 6 cycles of chemotherapy, patients in the Disney group felt less tense and worried less than patients in the control group according to their responses to the questions about emotional functioning (mean [SD] score, 86.9 [14.3] vs 66.3 [27.2]; maximum test P = .02). Furthermore, watching Disney movies was associated with less encroachment on patients' family life and social activities, as evaluated by the social functioning questions (mean [SD] score, 86.1 [23.0] vs 63.6 [33.6]; maximum test P = .01). Moreover, this intervention led to fewer fatigue symptoms (mean [SD] score, 85.5 [13.6] vs 66.4 [22.5]; maximum test P = .01). Perceived global health status was not associated with watching Disney movies (mean [SD] score, 75.9 [17.6] vs 61.0 [25.1]; maximum test P = .16). Conclusions and Relevance: These findings suggest that watching Disney movies during chemotherapy may be associated with improvements in emotional functioning, social functioning, and fatigue status in patients with gynecologic cancers. Trial Registration: ClinicalTrials.gov Identifier: NCT03863912.

Risk-adapted management for vasa praevia: a retrospective study about individualized timing of caesarean section.

PURPOSE: Vasa praevia is a rare condition with high foetal mortality if not detected prenatally. There is limited evidence available to determine the ideal timing of delivery and management recommendations. The aim of this study was to critically review our experience with vasa praevia, with a focus on diagnosis and management. METHODS: In a retrospective analysis, all cases of vasa praevia identified in our department from January 2003 to December 2017 were included. All cases were diagnosed antenatally during sonographic inspection of the placenta, and individualized management for each patient was performed based on individual risk factors. 19 cases of vasa praevia were identified (15 singletons, four twins). 13 patients (79%) presented placental anomalies. In patients at high risk for preterm birth, caesarean delivery was performed between 34-35 weeks after early hospitalization and administration of corticosteroids, whereas in patients at low risk for preterm birth, caesarean section could be delayed to 35-37 weeks of gestation. Administration of corticosteroids was not obligatory in the latter cases. RESULTS: There were two acute caesarean sections, due to premature abruption of the placenta and vaginal bleeding. There was no maternal or foetal/neonatal death. None of the neonates required blood transfusion. There is limited evidence available with which to determine the ideal timing of delivery. CONCLUSION: However, our individualized, risk-adapted management, which attempts to delay the timing of caesarean section up to two weeks beyond the standard recommendation, seems feasible, with just two emergency caesarean sections and no case of foetal or maternal death.

Prenatal detection of right aortic arch.

PURPOSE: To examine an unselective population of fetuses with right aortic arch (RAA) and suggest perinatal management. Second, to evaluate the importance and possible implication of fetal MRI in those cases. METHODS: Retrospective study of 36 patients with RAA diagnosed prenatally between 2006 and 2017 in a tertiary referral center. RESULTS: 32 fetuses were diagnosed with RAA and 4 with double aortic arch (DAA). 7 (19, 5%) cases had intracardiac abnormalities. Tetralogy of the Fallot was the most frequent one. Other extracardiac malformations were observed in 11/36 (30, 6%). Karyotype was available in 16 (44, 5%) cases. Two had 22q11.2 microdeletion, two trisomy 21, and one 20p12.2 duplication. Two needed surgery for respiratory symptoms. A newborn was identified with epilepsy, Lennox-Gastaud syndrome and Pallister-Killian syndrome postnatally and another one with showed hyperreflexia and premature closer of the fontanelle. Three feticides were performed for pregnancy termination in one case with 22q11 deletion, trisomy 21, and partial agenesis of corpus callosum. CONCLUSION: RAA can be detected by fetal echocardiography and it is associated with other cardiac or non-cardiac abnormalities, 22q11 microdeletion, trisomy 21, and other chromosomal abnormalities. karyotyping should be offered in any case of RAA, irrespective of co-existing malformations. Fetal MRI is a promising diagnostic tool for assessment of congenital cardiovascular abnormalities and extracardiac anomalies.

Does anti-Mullerian hormone predict the outcome of further pregnancies in idiopathic recurrent miscarriage? A retrospective cohort study.

PURPOSE: To evaluate whether anti-Mullerian hormone, basal follicle-stimulating hormone, luteinizing hormone, estradiol, and female age would predict future outcomes in women with idiopathic recurrent miscarriage. METHODS: One hundred and sixteen women with idiopathic recurrent miscarriage were retrospectively included. Luteal support with or without a combined treatment regimen for idiopathic recurrent miscarriage was applied in a tertiary-care center in Vienna. Occurrence and outcome of further pregnancies were analyzed. RESULTS: Within a median follow-up duration of 42.3 months, 94 women (81.0%) achieved one or more pregnancies. Further miscarriages occurred in 47 patients in whom only a higher number of previous miscarriages was predictive (OR 3.568, 95% CI 1.457-8.738; p = 0.005). Fifty-seven women had a live birth > 23 + 0 gestational weeks. In a multivariate analysis, age (OR 0.920, 95% CI 0.859-0.986; p = 0.019) and the number of previous miscarriages (OR 0.403, 95% CI 0.193-0.841; p = 0.016), but not AMH (OR 1.191, 95% CI 0.972-1.461; p = 0.091) were significantly predictive. CONCLUSION: AMH seems of either no or only minor relevance for the prediction of further miscarriages and live birth in women with idiopathic recurrent miscarriage.

Pharmacokinetic evaluation of the PNC disassembler metarrestin in wild-type and Pdx1-Cre;LSL-KrasG12D/+;Tp53R172H/+ (KPC) mice, a genetically engineered model of pancreatic cancer.

PURPOSE: Metarrestin is a first-in-class small molecule clinical candidate capable of disrupting the perinucleolar compartment, a subnuclear structure unique to metastatic cancer cells. This study aims to define the pharmacokinetic (PK) profile of metarrestin and the pharmacokinetic/pharmacodynamic relationship of metarrestin-regulated markers. METHODS: PK studies included the administration of single or multiple dose of metarrestin at 3, 10, or 25 mg/kg via intravenous (IV) injection, gavage (PO) or with chow to wild-type C57BL/6 mice and KPC mice bearing autochthonous pancreatic tumors. Metarrestin concentrations were analyzed by UPLC-MS/MS. Pharmacodynamic assays included mRNA expression profiling by RNA-seq and qRT-PCR for KPC mice. RESULTS: Metarrestin had a moderate plasma clearance of 48 mL/min/kg and a large volume of distribution of 17 L/kg at 3 mg/kg IV in C57BL/6 mice. The oral bioavailability after single-dose (SD) treatment was > 80%. In KPC mice treated with SD 25 mg/kg PO, plasma AUC0-∞ of 14400 ng h/mL, Cmax of 810 ng/mL and half-life (t1/2) of 8.5 h were observed. At 24 h after SD of 25 mg/kg PO, the intratumor concentration of metarrestin was high with a mean value of 6.2 µg/g tissue (or 13 µM), well above the cell-based IC50 of 0.4 µM. At multiple dose (MD) 25 mg/kg/day PO in KPC mice, mean tissue/plasma AUC0-24h ratio for tumor, spleen and liver was 37, 30 and 31, respectively. There was a good linear relationship of dosage to AUC0-24h and C24h. AUC0-24h MD to AUC0-24h SD ratios ranged from two for liver to five for tumor indicating additional accumulation in tumors. Dose-dependent normalization of FOXA1 and FOXO6 mRNA expression was observed in KPC tumors. CONCLUSIONS: Metarrestin is an effective therapeutic candidate with a favorable PK profile achieving excellent intratumor tissue levels in a disease with known poor drug delivery.

Reliability of sonographic fetal weight estimation in triplet pregnancies: a retrospective cohort study.

PURPOSE: To review our experience in ultrasound fetal weight estimation in our large population of triplet pregnancies. METHODS: Ninety-seven triplet pregnancies were retrospectively included between January 2003 and January 2017. Sonographic fetal weight estimation using Hadlock's and Schild's formulas was compared to actual birth weight in a tertiary-care center in Vienna, Austria. Statistical analyses were performed using a stepwise linear regression model and crosstabs. RESULTS: The median discrepancy between the sonographically estimated fetal weight by Hadlock's formula and the actual birth weight was 106 g (IQR 56-190). The percentage error and its standard deviation were - 2.5 ± 12.1%, and the median percentage error was - 3.6%. Concerning the use of Hadlock's formula, estimated fetal weight was the most important factor predictive of actual birth weight with an estimate of 0.920 (p < 0.001). Female neonates had been overestimated by a mean of 50.473 g per fetus. The sonographic prediction of small-for-gestational-age neonates was significantly reliable (p < 0.001), with positive and negative predictive values ranging from 81.3 to 100.0%. Similar results were obtained for Schild's formula. CONCLUSION: Even if sonographically estimated fetal weight in triplet pregnancies has a high overall accuracy of fetal weight estimation, there are some limitations in prediction of intrauterine growth restrictions, especially in female fetuses.

Fetal Survival in Second-Trimester Termination of Pregnancy Without Feticide.

OBJECTIVE: To evaluate the rate of live birth and the duration of survival after termination of pregnancy without feticide. METHODS: We conducted a retrospective analysis of 241 terminations of pregnancy without feticide for fetal anomalies or genetic abnormalities between 20 0/7 and 24 0/7 weeks of gestation at a single tertiary care referral center in Europe between February 2003 and May 2017. A multivariate binary regression model was used to evaluate factors associated with live birth. RESULTS: Pregnancies were terminated at a mean gestational age of 22.1±1.1 completed weeks of gestation. Median birth weight was 440 g (range 141-1,890 g). Live birth occurred in 122 cases (50.6%, 95% CI 44.4-56.8); median survival time was 32 minutes (range 1-267 minutes). Factors associated with live birth were gestational age at labor induction (odds ratio 1.41, 95% CI 1.01-2.01; P=.049) and fetal anomalies (P=.046). CONCLUSION: After termination of pregnancy without feticide between 20 0/7 and 24 0/7 weeks of gestation, the live birth rate was 50.6% (95% CI 44.4-56.8). A lower gestational age at labor induction and the presence of skeletal, cerebral, renal, or multiple fetal anomalies increased the chance of stillbirth.

Maternal and neonatal omentin-1 levels in gestational diabetes.

PURPOSE: To evaluate the effect of gestational diabetes on omentin-1 in maternal and cord plasma. As a potent mediator of insulin resistance, Omentin-1, an adipokine derived from human adipose and placental tissue, may be an important player in the pathophysiology of gestational diabetes. METHODS: This was a prospective case-control study. The study included 96 women with gestational diabetes and 96 pregnant women without. Omentin-1 was measured at the time of the oral glucose tolerance test, at 32 weeks in maternal plasma and right after delivery in umbilical cord blood by ELISA assay. RESULTS: Over a period of 2 years, 200 patients were enrolled. Omentin-1 levels did not significantly differ between both groups throughout the pregnancy: omentin-1 levels were 157 ± 83 ng/ml in women with gestational diabetes and 158 ± 93 ng/ml in women without gestational diabetes (p = 0.94) at time of the oral glucose tolerance test and 118 ± 77 ng/ml in women with diabetes and 150 ± 89 ng/ml in women without (p = 0.12) at 32 weeks, respectively. Both groups showed a decrease in omentin-1 levels throughout pregnancy, with a more pronounced decrease in diabetic women (13 ± 53 versus 4 ± 48 ng/ml; p = 0.5). Neonatal omentin-1 levels were significantly lower in offspring of diabetic mothers: 106 ± 61 versus 134 ± 45 ng/ml (p = 0.03). CONCLUSIONS: There was no significant difference in omentin-1 levels between healthy and diabetic mothers throughout the pregnancy. However, we found significantly lower omentin-1 levels in offspring of diabetic mothers. This may indicate a risk for the development of insulin resistance in later life.