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Objective: Omphalocele is known to be associated with genetic anomalies like trisomy 13, 18 and Beckwith-Wiedemann syndrome, but not with Turner syndrome (TS). Our aim was to assess the incidence of omphalocele in fetuses with TS, the phenotype of this association with other anomalies, their karyotype, and the fetal outcomes., Method: Retrospective multicenter study of fetuses with confirmed diagnosis of TS. Data were extracted from a detailed questionnaire sent to specialists in prenatal ultrasound., Results: 680 fetuses with TS were included in this analysis. Incidence of small omphalocele in fetuses diagnosed ≥12 weeks was 3.1%. Including fetuses diagnosed before 12 weeks, it was 5.1%. 97.1% (34/35) of the affected fetuses had one or more associated anomalies including increased nuchal translucency (≥3 mm) and/or cystic hygroma (94.3%), hydrops/skin edema (71.1%), and cardiac anomalies (40%). The karyotype was 45,X in all fetuses. Fetal outcomes were poor with only 1 fetus born alive., Conclusion: TS with 45,X karyotype but not with X chromosome variants is associated with small omphalocele. Most of these fetuses have associated anomalies and a poor prognosis. Our data suggest an association of TS with omphalocele, which is evident from the first trimester., (© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Mirror syndrome is a rare and serious maternal condition associated with immune and non-immune fetal hydrops after 16 weeks of gestational age. Subjacent conditions associated with fetal hydrops may carry different risks for Mirror syndrome. Fetuses with Turner syndrome are frequently found to be hydropic on ultrasound. We designed a retrospective multicenter study to evaluate the risk for Mirror syndrome among pregnancies complicated with Turner syndrome and fetal hydrops. Data were extracted from a questionnaire sent to specialists in maternal fetal medicine in Germany. Out of 758 cases, 138 fulfilled our inclusion criteria and were included in the analysis. Of the included 138, 66 presented with persisting hydrops at or after 16 weeks. The frequency of placental hydrops/placentomegaly was rather low (8.1%). Of note, no Mirror syndrome was observed in our study cohort. We propose that the risk of this pregnancy complication varies according to the subjacent cause of fetal hydrops. In Turner syndrome, the risk for Mirror syndrome is lower than that reported in the literature. Our observations are relevant for clinical management and parental counseling.

Migration allows animals to exploit spatially separated and seasonally available resources at a continental to global scale. However, responding to global climatic changes might prove challenging, especially for long-distance intercontinental migrants. During glacial periods, when conditions became too harsh for breeding in the north, avian migrants have been hypothesized to retract their distribution to reside within small refugial areas. Here, we present data showing that an Afro-Palearctic migrant continued seasonal migration, largely within Africa, during previous glacial-interglacial cycles with no obvious impact on population size. Using individual migratory track data to hindcast monthly bioclimatic habitat availability maps through the last 120,000 y, we show altered seasonal use of suitable areas through time. Independently derived effective population sizes indicate a growing population through the last 40,000 y. We conclude that the migratory lifestyle enabled adaptation to shifting climate conditions. This indicates that populations of resource-tracking, long-distance migratory species could expand successfully during warming periods in the past, which could also be the case under future climate scenarios., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Curated global climate data have been generated from climate model outputs for the last 120,000 years, whereas reconstructions going back even further have been lacking due to the high computational cost of climate simulations. Here, we present a statistically-derived global terrestrial climate dataset for every 1,000 years of the last 800,000 years. It is based on a set of linear regressions between 72 existing HadCM3 climate simulations of the last 120,000 years and external forcings consisting of CO 2 , orbital parameters, and land type. The estimated climatologies were interpolated to 0.5° resolution and bias-corrected using present-day climate. The data compare well with the original HadCM3 simulations and with long-term proxy records. Our dataset includes monthly temperature, precipitation, cloud cover, and 17 bioclimatic variables. In addition, we derived net primary productivity and global biome distributions using the BIOME4 vegetation model. The data are a relevant source for different research areas, such as archaeology or ecology, to study the long-term effect of glacial-interglacial climate cycles for periods beyond the last 120,000 years., (© 2021. The Author(s).)

Whilst an African origin of modern humans is well established, the timings and routes of their expansions into Eurasia are the subject of heated debate, due to the scarcity of fossils and the lack of suitably old ancient DNA. Here, we use high-resolution palaeoclimate reconstructions to estimate how difficult it would have been for humans in terms of rainfall availability to leave the African continent in the past 300k years. We then combine these results with an anthropologically and ecologically motivated estimate of the minimum level of rainfall required by hunter-gatherers to survive, allowing us to reconstruct when, and along which geographic paths, expansions out of Africa would have been climatically feasible. The estimated timings and routes of potential contact with Eurasia are compatible with archaeological and genetic evidence of human expansions out of Africa, highlighting the key role of palaeoclimate variability for modern human dispersals., (© 2021. The Author(s).)

Increasing body and brain size constitutes a key macro-evolutionary pattern in the hominin lineage, yet the mechanisms behind these changes remain debated. Hypothesized drivers include environmental, demographic, social, dietary, and technological factors. Here we test the influence of environmental factors on the evolution of body and brain size in the genus Homo over the last one million years using a large fossil dataset combined with global paleoclimatic reconstructions and formalized hypotheses tested in a quantitative statistical framework. We identify temperature as a major predictor of body size variation within Homo, in accordance with Bergmann's rule. In contrast, net primary productivity of environments and long-term variability in precipitation correlate with brain size but explain low amounts of the observed variation. These associations are likely due to an indirect environmental influence on cognitive abilities and extinction probabilities. Most environmental factors that we test do not correspond with body and brain size evolution, pointing towards complex scenarios which underlie the evolution of key biological characteristics in later Homo.

Objective:  Congenital corrected transposition of the great arteries (ccTGA) is a rare congenital cardiac anomaly which remains difficult to diagnose prenatally. We aim to investigate the natural history, associated anomalies and the outcome of patients in prenatally diagnosed ccTGA., Method:  This was an international multicenter retrospective analysis of fetuses with a diagnosis of ccTGA from 2002 to 2017. We reviewed clinical and echocardiographic databases of seven centers. Anatomic survey and fetal echocardiography were performed according to international guidelines of ISUOG., Results:  We considered 69 fetuses with prenatally suspected ccTGA. There was an overall survival rate of 91 % among 54 patients with a confirmed diagnosis. Survival to live birth was 96 % (52/54) and survival on an intention-to-treat basis was 94 % (49/52). The mean gestational age at the time of diagnosis was 25.6 ± 5.9 weeks of gestation. In 7 out of 54 fetuses (13 %), ccTGA was an isolated finding. Dextro/mesocardia was present in 15 cases (27.8 %). Intracardiac anomalies were present in 46/54 cases (85.2 %) with the most frequent anomaly being a ventricular septal defect present in 41 fetuses (75.9 %). Complete heart block was diagnosed in 10 cases (18.5 %). Extracardiac anomalies were observed in 9 out of 54 cases (16.7 %). Prenatal karyotyping of the fetus was available in 30/54 (55.6 %) cases with chromosomal anomalies in 4/30 (13.3 %)., Conclusion:  ccTGA is a rare cardiac anomaly often accompanied by a variable spectrum of further intracardiac abnormalities. Accurate diagnosis of ccTGA, which can be integrated into parental counselling, is feasible with a favorable short-term outcome for affected neonates., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

The variability of climate has profoundly impacted a wide range of macroecological processes in the Late Quaternary. Our understanding of these has greatly benefited from palaeoclimate simulations, however, high-quality reconstructions of ecologically relevant climatic variables have thus far been limited to a few selected time periods. Here, we present a 0.5° resolution bias-corrected dataset of global monthly temperature, precipitation, cloud cover, relative humidity and wind speed, 17 bioclimatic variables, annual net primary productivity, leaf area index and biomes, covering the last 120,000 years at a temporal resolution of 1,000-2,000 years. We combined medium-resolution HadCM3 climate simulations of the last 120,000 years with high-resolution HadAM3H simulations of the last 21,000 years, and modern-era instrumental data. This allows for the temporal variability of small-scale features whilst ensuring consistency with observed climate. Our data make it possible to perform continuous-time analyses at a high spatial resolution for a wide range of climatic and ecological applications - such as habitat and species distribution modelling, dispersal and extinction processes, biogeography and bioanthropology.

Our understanding of how global climatic changes are translated into ice-sheet fluctuations and sea-level change is currently limited by a lack of knowledge of the configuration of ice sheets prior to the Last Glacial Maximum (LGM). Here, we compile a synthesis of empirical data and numerical modelling results related to pre-LGM ice sheets to produce new hypotheses regarding their extent in the Northern Hemisphere (NH) at 17 time-slices that span the Quaternary. Our reconstructions illustrate pronounced ice-sheet asymmetry within the last glacial cycle and significant variations in ice-marginal positions between older glacial cycles. We find support for a significant reduction in the extent of the Laurentide Ice Sheet (LIS) during MIS 3, implying that global sea levels may have been 30-40 m higher than most previous estimates. Our ice-sheet reconstructions illustrate the current state-of-the-art knowledge of pre-LGM ice sheets and provide a conceptual framework to interpret NH landscape evolution.

Wild horses thrived across Eurasia until the Last Glacial Maximum to collapse after the beginning of the Holocene. The interplay of climate change, species adaptability to different environments, and human domestication in horse history is still lacking coherent continental-scale analysis integrating different lines of evidence. We assembled temporal and geographical information on 3070 horse occurrences across Eurasia, frequency data for 1120 archeological layers in Europe, and matched them to paleoclimatic and paleoenvironmental simulations for the Late Quaternary. Climate controlled the distribution of horses, and they inhabited regions in Europe and Asia with different climates and ecosystem productivity, suggesting plasticity to populate different environments. Their decline in Europe during the Holocene appears associated with an increasing loss and fragmentation of open habitats. Europe was the most likely source for the spread of horses toward more temperate regions, and we propose both Iberia and central Asia as potential centers of domestication.

In the 1980s, it was demonstrated that semi-volatile organic compounds (SVOCs) like polychlorinated biphenyls (PCBs) accumulate in plant leaves. Plants are at the base of the food chain, and therefore a starting point for transfer of PCBs to animals and related human exposure. For two decades, the Environment Agency of the German federal state of Bavaria (LfU) has been operating long-term monitoring stations to measure the impact of organic air pollutants. Standardized ryegrass, curly kale, and spruce needles are used as bioindicators for the atmospheric entries of PCBs into vegetation. From the end of 1990s to 2009, there was a marked decline in the concentrations of indicator PCBs (i-PCBs) and a minor decline in PCB-TEQ levels. After 2009, the concentrations leveled off. In rural areas, the median concentrations of Σ6 i-PCB in ryegrass and curly kale were about 3 and 4 μg/kg dm in 2000, and have been about 0.5 and 1 μg/kg dm since 2009, respectively. Concentrations in spruce needles fell from 0.9 to 0.4 μg/kg dm. Median PCB-TEQ concentrations in the bioindicator plants ranged from 0.05 to 0.23 ng/kg dm between 2002 and 2009 and from 0.15 to 0.05 ng/kg dm after 2009. Indicator PCB and PCB-TEQ concentrations were several times higher at the urban station in Munich than at the rural areas, reflecting the emissions from in-use PCB stocks in the building sector. The likely reason of the slower decrease of PCB-TEQ compared to i-PCBs is the formation of PCB-126 by dechlorination of industrial PCBs in open applications.

Purpose: To scrutinize the characteristics of all cases with antenatally established diagnosis of cephalocele in two tertiary referral centers., Methods: We retrospectively reviewed 65 cases diagnosed with cephaloceles and tabulated sonographic findings and autopsy recordings as well as medical charts of all survivors in terms of clinical outcome., Results: The case notes of 65 fetuses were available for final analysis. Gestational age (GA) at diagnosis ranged from 10.4 to 38.1 weeks. Of our cohort, 53/65 cases (80%) had occipital protrusions, 10 (15%) were found to have frontal lesions, and another two had parietal cephaloceles. A total of 52 pregnancies were terminated or resulted in intrauterine fetal demise (78%). In 18 cases (11%), the cephalocele was part of underlying syndromic disorders (e.g., Meckel-Gruber syndrome). Thirteen pregnancies were continued until term, out of which all affected individuals were live-born. Neurosurgical intervention was prompted within the first 7 months postnatally., Conclusions: In general, the outcome of fetuses with cephaloceles is rather poor as four out of five pregnancies were terminated. Postnatal outcome of all survivors in our cohort was rather determined by localization of the cele and more important by the presence and severity of concomitant malformations than the extent of the lesion.

Objective: The objective of this study was to analyze the spectrum of prenatally diagnosed absent pulmonary valve syndrome (APVS) and the outcome from diagnosis onwards. Fetuses with APVS and tetralogy of Fallot (TOF/APVS) and with APVS and intact ventricular septum (APVS/IVS) were included., Method: Multicenter retrospective study of the International Prenatal Cardiology Collaboration Group. Clinical and echocardiographic databases of nine referral centers were reviewed from 2012-2016., Results: The cohort included 71 cases, 59 with TOF/APVS and 12 with APVS/IVS. In 18.3% of cases, diagnosis was achieved within first trimester. Association with hydrops fetalis was high within first trimester (69%). No fetus with known outcome survived after first trimester diagnosis. Karyotype anomalies occurred in 45% of cases with known karyotype. Intrauterine fetal demise occurred in 14.3%. Overall survival after initial diagnosis in the total cohort was 28.1% (28.8% TOF/APVS and 25.0% APVS/IVS). Survival to birth was 50% in TOF/APVS and 44.4% in APVS/IVS. Survival of subjects born alive beyond neonatal period was 84.6% in TOF/APVS and 100% in APVS/IVS., Conclusion: Diagnosis of APVS is feasible within first trimester. Outcomes remain guarded, especially if first trimester diagnosis is included into the analysis because of associated karyotypic anomalies, the presence of hydrops fetalis, and patent ductus arteriosus. © 2017 John Wiley & Sons, Ltd., (© 2017 John Wiley & Sons, Ltd.)

Background: Disease-independent sources of biomarker variability include pre-analytical, analytical and biological variance. The aim of the present study was to evaluate whether the pre-analytical phase has any impact on the emerging heart disease TWEAK and HMGB1 protein markers and miRNA biomarkers, and whether peptidome profiling allows the identification of pre-analytical quality markers., Methods: An assessment was made of sample type (serum, EDTA-Plasma, Citrate-Plasma, ACD-plasma, Heparin-plasma), temperature of sample storage (room temperature or refrigerated), time of sample storage (0.5, 3, 6 and 9h) and centrifugation (one or two-step). Aliquots of all processed samples were immediately frozen (-80°C) before analysis. Proteins were assayed by ELISAs, miRNA expression profile by microarray and peptidome profiling by MALDI-TOF/MS., Results: Temperature, time and centrifugation had no impact on TWEAK and HMGB1 results, which were significantly influenced by matrix type, TWEAK levels being significantly higher (F=194.7, p<0.0001), and HMGB1 levels significantly lower (F=36.32, p<0.0001) in serum than in any other plasma type. Unsuitable miRNA results were obtained using Heparin-plasma. Serum miRNA expression profiles depended mainly on temperature, while EDTA-plasma miRNA expression profiles were strongly affected by the centrifugation method used. MALDI-TOF/MS allowed the identification of seven features as indices of pre-analytical serum (m/z at 1206, 1350, 1865 and 2021) or EDTA-plasma (m/z 1897, 2740 and 2917) degradation., Conclusions: Serum and EDTA-plasma allow the analysis of both proteins and miRNA emerging biomarkers of heart diseases. Refrigerated storage prevents an altered miRNA expression profile also in cases of a prolonged time-interval between blood drawing and processing., (Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Purpose  The introduction of first trimester screening has changed the attitude towards and the number of invasive procedures in prenatal medicine. We evaluated the indications in patients who underwent an invasive procedure before the introduction of the analysis of cell-free fetal DNA in maternal plasma in prenatal medicine. Materials and Methods  680 pregnant women between the 10th and 35th week of gestation were included in the study from July 1, 2010 to June 30, 2013. Retrospectively, we reviewed the data for indications, type, gestational age at the time of, and result of the invasive procedure. Results  We performed 247 chorionic villus samplings (CVSs) and 433 amniocenteses (ACs) during the study interval. The main indication for CVS was an abnormal result from the first trimester screening (75 %), whereas in AC it was advanced maternal age (39 %). 33 % of all CVSs and 8 % of all ACs revealed an abnormal karyotype. All these findings were significantly different. Conclusion  Despite the broad acceptance of first trimester screening, there are still women undergoing AC for advanced maternal age, whereas abnormal results from the first trimester screening are the most common indication for CVS. Based on our results, we can conclude that indications derived from first trimester findings have the highest positive predictive value., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: The aim of the study was to describe the response of fetal lung vasculature to maternal hyperoxygenation (MH) in the case of prenatally diagnosed hypoplastic left heart (HLH) with intact or restrictive (IAS/RAS) and without restriction of the atrial septum. Furthermore, the ability of MH to differentiate between newborns with HLH who do not require immediate atrial septostomy and newborns who will undergo immediate left atrial septoplasty after birth was evaluated., Materials and Methods: Cross-sectional prospective study of fetuses ≥ 26 weeks of gestation with prenatally diagnosed HLH. Lung perfusion (LP) was qualitatively assessed by color Doppler interrogation and LP was quantitatively measured using the pulsatility index for veins (PIV). Measurements were performed both with the mother breathing room air (LPRA) and after receiving 100% oxygen for 10 minutes (LPMH). The oxygen test was defined as positive if MH led to an increase in lung perfusion and as negative if MH did not lead to an increase., Results: A total number of 22 pregnancies with hypoplasia of the left heart structures were included. 6/20 cases presented with an intact or restrictive atrial septum (IAS/RAS). All of these fetuses presented with a reduced LPRA. MH led to an increase in LP in 2/6 cases. The overall 30-day-survival rate was 83.3% (5/6). In 14/20 fetuses an open septum was detected. 11 cases had a normal LPRA, and the LPRA was reduced in 3/14 fetuses. The overall 30-day-survival rate was 92.9% (13/14)., Conclusion: MH might be a useful adjunct in the assessment of pulmonary vasculopathy in fetuses with HLH., (© Georg Thieme Verlag KG Stuttgart · New York.)

Validation of biomarkers is essential to advance the translational process to clinical application. Although there exists an increasing number of reports on small non-coding RNAs (microRNAs) as minimally-invasive markers from blood, serum or plasma, just a limited number is verified in follow-up studies. We used qRT-PCR to evaluate a known miRNA signature measured from blood that allowed for separation between patients with non-small cell lung cancer (NSCLC), COPD and healthy controls.From the data of our previous microarray studies we selected a panel of 235 miRNAs related to lung cancer and COPD. We observed a high concordance between the AUC values of our initial microarray screening and the qRT-PCR data (correlation of 0.704, p < 10-16). Overall, 90.3% of markers were successfully validated. Among the top markers that were concordant between both studies we found hsa-miR-20b-5p, hsa-miR-20a-5p, hsa-miR-17-5p, and hsa-miR-106a-5p. The qRT-PCR analysis also confirmed that non-small cell lung cancer patients could be accurately differentiated from unaffected controls: a subset of five markers was sufficient to separate NSCLC patients from unaffected controls with accuracy of 94.5% (specificity and sensitivity of 98% and 91%). Beyond differentiation from controls, we also succeeded in separating NSCLC patients from patients with COPD. MiRNAs that were identified as relevant for the separation between lung cancer and COPD by both qRT-PCR and the array-based studies included hsa-miR-26a-5p, hsa-miR-328-3p and hsa-miR-1224-3p. Although for differentiation between NSCLC patients from COPD patients more markers were required, still high accuracy rates were obtained (5 markers: 78.8%; 10 markers: 83.9%; 50 markers: 87.6%).

Objective: To evaluate patterns of fluid allocations in different etiologies of hydrops fetalis., Study Design: This report is a retrospective cohort study on 20,395 fetal sonographic evaluations in a single tertiary center from 2000 to 2014. Special emphasis was placed on the exact description of the distinct fluid allocation sites in each fetus. Postmortem/postnatal records were evaluated additionally. Mean follow up of the surviving neonates was 34 days (10-60 days)., Results: There seem to be distinctive patterns of fluid allocation in some etiologies leading to fetal hydrops including aneuploidies and Parvovirus B19 related infections., Conclusion: Due to the allocation patterns of fluid filled sites in fetuses with hydrops fetalis the spectrum of possible etiologies may be narrowed already during initial ultrasound scan. It can contribute substantially to diagnostic accuracy as well as to parental counseling. This knowledge may also help to omit delay in diagnostic routines., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background & Patient: Data from 3 008 patients, who underwent single-nucleotide-polymorphism (SNP)-based noninvasive prenatal testing (NIPT) are presented., Method: The PanoramaTM test (Natera, San Carlos, CA) was used to analyze cell-free fetal DNA from maternal blood for trisomies 21, 18, and 13, triploidy and sex-chromosome aneuploidies., Result: In 2 942 (97.8%) cases, a result was obtained. The average fetal fraction was 10.2%. A high-risk result for fetal aneuploidy was made for 65 (2.2%) cases. In 59 (90.8%) of these cases, invasive testing confirmed the aneuploidy. There were 6 false-positive cases. In the false-positive group, the fetal fraction was significantly lower. The overall positive predictive value was 90.8%. No false-negative cases were reported but many patients in this study have not delivered yet. Therefore, exact data cannot be given for potential false-negative cases., Conclusion: SNP-based NIPT is a reliable screening method for evaluating the risk of aneuploidies of chromosomes 21, 18 and 13. By using NIPT, the number of invasive procedures may be reduced significantly compared to maternal age and first-trimester screening.

Purpose: The purpose of this study was to classify pregnancy loss and fetal loss as well as the influence of maternal risk factors in multiple pregnancies., Methods and Materials: Details of the procedure and pregnancy outcome of all patients were extracted from the clinical audit database of two tertiary centers. The files were collected in the time from January 1993 to May 2011.  The procedure-related pregnancy and fetal loss rate was classified as all unplanned abortions without important fetal abnormalities or obstetric complications within 14 days after AC and CVS., Results: We had a total number of 288 multiple pregnancies with a total of 637 fetuses. After the exclusion of 112 pregnancies with abnormal karyotype or fetal abnormalities detected by ultrasound as well as cases of selective feticide, repeated invasive procedures and monochorionic-monoamniotic pregnancies, 176 pregnancies and 380 fetuses were left for final analysis. Overall 132 amniocenteses and 44 chorionic villous sampling procedures were performed. The total pregnancy loss rate was 8.0 % (14/176), 6.1 % (n = 8) for amniocentesis and 13.6 % (n = 6) for CVS.  The procedure-related pregnancy loss rate was 3.4 %, 2.3 % after amniocentesis (3 cases) and 6.8 % after CVS (3 cases). There was no statistical significance between the two procedures (p = 0.15)., Conclusion: The procedure-related loss rate of 3.4 % can be compared to the rates in the literature. The higher loss rates in multiple pregnancies than in singleton pregnancies have to be discussed when counseling parents., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: Hypoplastic left heart (HLH) is one of the most common forms of cardiac abnormality detectable during gestation by fetal echocardiography. Antenatal diagnosis allows for appropriate counseling and time to consider treatment options. We report the actual outcome data after fetal diagnosis of HLH., Materials and Methods: Retrospective analysis of the outcome in all cases with HLH from 1994 - 2011 presenting in fetal life at two tertiary referral centers for prenatal diagnosis and pediatric cardiology., Results: 105 cases were included and the overall survival is 40.9 % (43/105) after prenatal diagnosis. There was an 81.1 % survival rate in infants undergoing surgery and a 64.1 % survival rate from an intention-to-treat position. Two neonates died due to tamponade and cardiac arrest following balloon septostomy and one neonate from sepsis before surgery. Extracardiac anomalies occurred in three fetuses, and karyotype anomalies in seven fetuses (18.9 %). In 4 of 5 babies born with additional extracradiac or karyotype anomalies, parents opted for compassionate care. The first had trisomy 13, the second had trisomy 18, the third neonate presented with spina bifida, and the fourth presented with hydronephrosis and pulmonary atresia. Termination of pregnancy took place in 17 cases (16.1 %)., Conclusion: Thorough antenatal evaluation should include karyotyping, detailed extracardiac and intracardiac assessment to accurately predict the risks of surgery. Prenatal counseling might be modified after the exclusion of additional anomalies. These data provide up-to-date information for parental counseling., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To assess the total and procedure-related fetal loss rate and associated risk factors following amniocentesis (AC), chorionic villus sampling (CVS) and fetal blood sampling (FBS)., Materials and Methods: We performed a retrospective analysis of patients with invasive diagnostics from 1993 to 2011 in two tertiary referral centers. We aimed to classify pregnancy loss after an invasive procedure and included the time after the invasive procedure and the result of targeted ultrasound/karyotype analysis in the analysis. Fetal losses occurring within two weeks after an invasive procedure were classified as procedure-related., Results: After excluding 1553 pregnancies with abnormal karyotype, fetal malformations and multiple insertions, 6256 cases were retrieved for final analysis. The total fetal loss rate was 1.5 %. The procedure-related fetal loss rate was 0.4 % for AC, 1.1 % for CVS and 0.4 % for FBS. Maternal vaginal bleeding in the first trimester was significantly associated with an increased procedure-related fetal loss rate (p= 0.008). The number of invasive procedures declined during the study period with increasing numbers of CVS in the first trimester., Conclusion: In our population the procedure-related fetal loss rate was 0.4 % after AC and 1.1 % and 0.4 % after CVS and FBS, respectively. Different gestational ages at the time of invasive procedures might account in part for those differences. Vaginal bleeding during the first trimester is associated with increased procedure-related fetal loss. Overall, declining numbers of invasive procedures are the result of changing attitudes toward invasive procedures and more sophisticated noninvasive prenatal screening programs over the last 20 years., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: To evaluate the prenatal features, associated anomalies and the postnatal management in fetuses with prenatally detected double-outlet right ventricle (DORV)., Methods: Retrospective analysis of prenatal, pediatric and cardiosurgical records for all fetuses with prenatally diagnosed DORV at a single tertiary referral center., Results: 21 cases were detected prenatally with DORV (average gestational age 23(3/7) weeks). Fetal karyotyping was available in all cases revealing 3 cases with trisomy 18 and one fetus with trisomy 21. 10/21 (47.6%) cases had additional cardiac anomalies only, one fetus (4.8%) had extra-cardiac anomalies only. 8/21 cases (38.1%) presented with both additional cardiac- and extra-cardiac anomalies. A total of 13/21 (61.9%) fetuses were live-born. Average gestational age at delivery was 37(3/7) gestational weeks. There were four Rastelli maneuvers, one Fontan intervention and three children with resection of a coarctation of the aorta among the group of the surviving infants., Conclusions: Prenatal, sonographic detection of DORV is feasible. The majority of the cases shows a normal karyotype. Outcome strongly depends on the presence and severity of additional anomalies of the fetus. Surgical intervention in DORV can lead to a favorable outcome in simple DORV. DORV not aggravated by additional defects seems to be no contraindication for a vaginal delivery.

Objectives: Fetal ductus venosus (DV) blood flow velocity waveforms are significantly altered during contractions in first stage of labor. We have evaluated the reproducibility of these waveforms during and between contractions., Methods: 90 women between 37th and 41st week of gestation were included in the study. The measurements of the DV were obtained by three different investigators during and between contractions. The pulsatility index for veins (PIV), peak velocity index for veins (PVIV), and fetal heart rate (FHR) were calculated offline. Furthermore, differences in PVIV (PVIVdiff) and PIV (PIVdiff) and a mean of FHR (FHRmean) were calculated. Statistical analysis was used to verify differences in the PIV, PVIV and FHR during and between contractions of each subgroup as well as for the PVIVdiff, PIVdiff and FHRmean between the subgroups., Results: Investigator 1 examined 49 patients (group 1); investigator 2, 17 patients (group 2) and investigator 3, 24 patients (group 3), respectively. In all subgroups, there was a significant difference for the PVIV and PIV during and between contractions, but not for FHR. There was a correlation between gestational age and PVIVdiff, PIVdiff and FHRmean as well as for maternal age and PVIVdiff and PIVdiff. PVIVdiff and PIVdiff showed significant differences in group 1 compared to groups 2 and 3 (p < 0.001), but not between groups 2 and 3., Conclusions: Significant differences in the measurements in the three subgroups have been revealed, which may be due to different timing of measurement during the contraction. For future studies further standardization of the measurement protocol should be established.

Purpose: The aim of this study was the follow-up of children with a prenatal diagnosis of tachyarrhythmia up to an age of 5 years in order to assess the long-term outcome of these children., Materials and Methods: All fetuses diagnosed with prenatal tachyarrhythmia between April 1993 and June 2004 in the Division of Prenatal Medicine, Department of Obstetrics and Gynecology, University Hospital of Schleswig-Holstein, Campus Lübeck were identified and the children's parents and pediatricians were contacted for retrospective data on the children's health. The data from the compulsory examinations (U1-U9) were used for analysis., Results: 49 cases (93%) were enrolled in this study. 23 fetuses had supraventricular tachycardia (SVT), 10 had an atrial flutter (AF) and 16 had paroxysmal supraventricular tachycardia (pSVT). Intrauterine conversion into sinus rhythm was achieved in 41 of 44 treated fetuses (93%). 17 of 48 cases showed tachyarrhythmia postnatally (35%). 15 of these newborns were treated with antiarrhythmic medication between 4 days and 46 months. The follow-up rate in the 3 subgroups ranged from 78-100%. At the time of the U9 examination, 69-100% of the children were healthy. During the examinations there was an increase in motor activity delay and language development delay with a maximum at U5 and U9, respectively., Conclusion: Overall, on the basis of the long-term follow-up of 49 children, we could show that prenatal tachyarrhythmia has a good prognosis. Increased motor activity and language development delay are important for patient counseling. Substantial cardiac and extracardiac anomalies are associated with an unfavorable outcome., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: The aim of this study is to evaluate the cumulative detection rate of foetal echocardiography during gestation and in the early neonatal period, with a special emphasis on early foetal echocardiography., Methods: We conducted a retrospective survey of all singleton pregnancies from 1993 to 2007, with complete sequential echocardiography from 11 plus 0 to 13 plus 6 weeks of gestation. It was mandatory to have at least one foetal echocardiography in the second or third trimester and one postnatally., Results: Our study included 3521 pregnancies, in which 77 cases were diagnosed with congenital heart disease. Of them, 66 were detected in the first trimester - 11 plus 0 to 11 plus 6 weeks: 22 cases; 12 plus 0 to 12 plus 6 weeks: 23 cases; 13 plus 0 to 13 plus 6 weeks: 21 cases - with an 85.7% detection rate of congenital heart disease in early foetal echocardiography. In the second trimester, seven cases were found, with a detection rate of 9.1%. The third trimester reported two cases, with a detection rate of 2.6%. Postnatally, two (2.6%) cases were detected. The overall in utero detection rate of congenital heart disease was 97.4%., Conclusions: Foetal echocardiography performed at the time of anomaly screening in the first trimester results in high detection rates of congenital heart disease. Cardiac pathology may evolve, and further examinations at later stages of pregnancy could improve the detection rate of congenital heart disease.

Purpose: The objective of this study was to evaluate which cardiac planes and malformations can be visualized by first trimester fetal echocardiography during the daily routine in a prenatal medicine unit., Materials and Methods: From October 2007 to June 2009, all fetuses with a crown rump length between 45 and 84 mm were included in the study. The fetal echocardiographies were carried out by one examiner. The entire examination including fetal echocardiography was completed within a time interval of 30 minutes. When possible, the abdominal plane, 4-chamber view (CV), pulmonary veins, left ventricular outflow tract, 3-vessel view (3-VV) and the aortic arch were visualized by color Doppler and/or power Doppler sonography., Results: 690 fetuses were enrolled in the retrospective study. The abdominal plane, 4-CV, pulmonary veins, left ventricular outflow tract, 3-VV and the aortic arch were visualized in 99 %, 96 %, 23 %, 97 %, 98 % and 72 % of cases, respectively. During the study interval, 17 cardiac malformations were diagnosed. Outcome data were obtained in 92 % of the normal fetuses. 5 cardiac anomalies were diagnosed beyond the first trimester., Conclusion: The standard planes of fetal echocardiography can be displayed in the first trimester in the clinical routine. Pulmonary veins can be visualized in almost a quarter of the cases. First trimester congenital heart diseases are strongly associated with chromosomal abnormalities during the first trimester., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To elaborate the antenatal sonographic findings of fetuses with the suspicion of fetal akinesia, thereby focusing on the accuracy of prenatal differentiation between subtypes of fetal akinesia, namely Pena-Shokeir phenotype (PSP) and arthrogryposis multiplex congenita (AMC)., Methods: We herein present our experience of 21 patients with PSP and AMC diagnosed antenatally at a tertiary prenatal referral center. During the study period 30,485 consecutive high- and low-risk pregnancies were examined. The prenatal sonograms, pediatric charts and autopsy data of affected individuals were reviewed. Our findings were analyzed together with findings retrieved from the literature., Results: The diagnosis of AMC has been established between 12+0 and 30+1 gestational weeks, whereas cases found to have PSP were all diagnosed in advanced pregnancy. In accordance to previous findings, our data suggest that pulmonary hypoplasia is obligatory in PSP and cannot be found in AMC. Therefore, all pregnancies (9/9) affected by PSP were terminated on parental request. Of those fetuses with AMC, 3/12 were liveborn, 2 of which have neuromotoric disabilities., Conclusions: Establishing the correct prenatal diagnosis of PSP and AMC at an early stage and its diligent prognostic evaluation play a crucial role in order to provide adequate advice to the afflicted parents and to enable appropriate intervention at an early stage., (Copyright © 2011 S. Karger AG, Basel.)

Purpose: The aim of this study was the follow-up of children with a prenatal diagnosis of supraventricular extrasystole (SVES) up to an age of 5 years in order to assess the long term outcome of these children and in order to characterize factors influencing the outcome., Materials and Method: All fetuses diagnosed with prenatal SVES between April 1993 and August 2005 were identified and the children's parents and pediatricians contacted for data regarding the children's health. Follow-up data about the children's health up to the age of 5 years could be obtained in 77 (46.1%) children., Results: 0.5% (167/34,770) of all fetuses were diagnosed with prenatal SVES. In 70% of cases the SVES resolved before or at birth. 30% of children presented with arrhythmia postpartum. 31% of children were diagnosed with cardiac anomalies postpartum. 87% of children were healthy at the age of 2 - 5 years. In the subgroup of children with isolated fetal SVES without further anomalies, 95% of children were healthy at the age of 2 - 5 years. In children with persisting arrhythmia and in children with cardiac anomalies, the prognosis was worse., Conclusions: Overall, by the long-term follow-up of 77 children with prenatal SVES we could show that prenatal SVES has a good prognosis. However, 30% of children develop arrhythmia postpartum and 31% of children present with cardiac anomalies. These children still have a worse prognosis than children with isolated prenatal SVES., (Georg Thieme Verlag KG Stuttgart, New York.)

Purpose: To report the course and outcome of a group of fetuses with prenatal suspicion of coarctation of the aorta., Materials and Methods: Retrospective observational study in two tertiary fetal cardiology centers between 1993 - 2005., Results: 96 fetuses of whom 52 infants were born alive were studied. Of the 52 liveborn infants, 34 had coarctation of the aorta (65.4 %), thirteen had prenatally diagnosed additional cardiac anomalies (VSD, ASD, aortic and pulmonary stenosis, persistent left superior vena cava) and three were managed as having hypoplastic left heart syndrome. Three neonates had additional extracardiac malformations diagnosed prenatally. 22 neonates underwent surgery, nineteen within the first ten days of life. One neonate only developed clinical signs of coarctation on the fourteenth day of life. The early surgical mortality was three of 22 (13.6 %). The mortality was influenced by prematurity. The survival rate on the basis of intention-to-treat was twenty-nine of 34 neonates with confirmed coarctation (85.3 %)., Conclusion: Coarctation of aorta during fetal life continues to be a difficult diagnosis. The potential of progressive hypoplasia of left heart structures during gestation in the case of fetal aortic isthmus stenosis with the development of a hypoplastic left heart should be kept in mind and therefore sequential echo-cardiography is recommended during gestation.

Purpose: To evaluate the associated conditions and the outcome of atrioventricular septal defects (AVSD) detected in fetal life., Materials and Methods: Retrospective review of all cases of AVSD detected prenatally between 1998 and 2006 in two tertiary referral centers in Germany., Results: 246 cases of AVSD were detected in the study period: 129 (52.4 %) chromosomal anomalies; 72 (29.3 %) heterotaxy syndromes; 17 (6.9 %) non-chromosomal malformation syndromes; 16 (6.5 %) isolated complex cardiac malformations; 5 (2.0 %) singular extracardiac malformations; 7 (2.8 %) isolated AVSD. Chromosomal anomalies were detected significantly earlier in pregnancy (p < 0.01). Associated intracardiac malformations were present in 109/246 (44.3 %) cases. Fetuses with trisomy 21 were significantly associated with balanced ventricular morphology and isolated AVSD (p < 0.01). Among the 246 cases, 144 (58.5 %) underwent termination of pregnancy, 18 (7.3 %) died in utero, 17 (6.9 %) in the neonatal period and 19 (7.7 %) in infancy. Forty-eight children (19.5 %) survived with a mean follow-up of 34.94 +/- 18.6 months. After exclusion of lethal malformations, the survival rate among live births was 64.9 % (48 / 74). Fetuses with trisomy 21 had significantly better survival rates among continued pregnancies (p < 0.01) and significantly higher rates of successful biventricular repair among survivors who received their final corrective procedure (p < 0.01) than fetuses with normal karyotypes., Conclusion: Among fetuses with AVSD, those with trisomy 21 are detected earlier in pregnancy, have less distorted cardiac anatomy, higher rates of biventricular repair and better survival rates. Due to the limited sample size in euploid fetuses, it remains unclear whether this apparent protection afforded to Down syndrome accounts also for cohorts with isolated and balanced AVSD.

We report a case of a fetus diagnosed with micro-retrognathism at routine ultrasound examination in the 22nd week of gestation. The diagnosis of Pierre-Robin syndrome was made postnatally. The possible differential diagnoses and the main complications of retrognathism are reviewed.

X-linked dominant chondrodysplasia punctata (Conradi-Hünermann disease, CDPX2) is characterised by short stature, stippled epiphyses, cataracts, ichthyosiform erythroderma and patchy alopecia of the scalp. The disorder is caused by mutations within the emopamil binding protein (EBP) gene encoding a 3beta-hydroxysteroid-Delta(8),Delta(7)-isomerase. The intrafamilial variation of disease severity is a known feature of CDPX2 probably caused by skewed X-inactivation. We report on a female fetus with typical symptoms of CDPX2 such as short limbs, postaxial polydactyly, ichthyotic skin lesions and punctate calcifications. Molecular genetic analysis of the EBP gene revealed a nonsense mutation (c.328C>T, p.R110X), which was previously detected in one CDPX2 patient and in a second female patient, who was only affected on one body side and erroneously diagnosed as CHILD syndrome. Surprisingly, the mother of our fetus carries the same mutation without having any signs of CDPX2. X-inactivation studies did not reveal any evidence of skewing neither in the mother nor in the fetus.

Aim: The purpose of the study was to investigate whether colour Doppler sonography is helpful in the surveillance of abnormal third stage of labour., Materials and Methods: 20 patients were enrolled in the prospective study. Inclusion criteria were third stage of labour > 15 min and/or clinical suspicion of retained placenta. By means of grey scale and colour Doppler sonography the length of distinct phases of third stage of labour and length of visualisation of blood flow between myometrium and placenta were measured. These data were compared with previously published normal values., Results: The patients were allocated into four groups: 1. Patients with prolonged third stage of labour, but normal vaginal delivery of the placenta (Group 1, 8 cases). 2. Patients with clinically suspected retained placental parts (Group 2, 4 cases). 3. Patients with manual removal of the placenta without confirmation of placenta accreta (Group 3, 4 cases). 4. Patients with manual removal of the placenta with confirmation of placenta accreta (Group 4, 4 cases). A significant longer latent phase was responsible for the prolonged third stage of labour in Group 1 (p < 0.05). Blood flow between myometrium and placenta was significantly longer visible in Group 4 than in the normal cohort (p < 0.0001)., Conclusion: Grey scale sonography can help to distinguish between uncomplicated and complicated prolonged third stage of labour. Colour Doppler sonography can detect persistent blood flow between myometrium and placenta during third stage of labour in cases of placenta accreta. In these instances, the patient may benefit from colour Doppler sonography-guided curettage.

Objective: To evaluate attitudes towards non-invasive aneuploidy screening at advanced maternal age in a German tertiary care centre and to compare the rate of invasive testing over a period of four years., Methods: A retrospective analysis of 2657 singleton pregnancies with targeted first and second trimester ultrasound examination at 11-14, 15-18 and 19-23 weeks' gestation., Results: The number of patients at or beyond 35 years increased by 36 % over this period. Concomitant with an increasing proportion of first trimester examinations (+ 13 %), a decrease in 15-18 weeks' examinations (- 14 %), but no changes regarding the 19-23 weeks' examination were observed. A total of 78 (2.9 %) abnormal karyotypes were found and 92 % (56/61) of the cases with autosomal trisomy had sonographic markers suggestive of foetal aneuploidy. The proportion of diagnosed chromosomal abnormalities at 11-14 weeks increased from 14 % in the first half to 49 % in the second half of the study period (p < 0.01). We observed a significant decrease in the rate of invasive procedures, especially in women reassured by a normal ultrasound examination (54 % versus 37 %, p < 0.01)., Conclusion: There is an increasing acceptance of first trimester targeted ultrasound examination with the potential advantage of an earlier diagnosis of foetal aneuploidy. Furthermore, we observed annually increasing numbers of women who used the results of the ultrasound examination to guide their final decision about invasive testing, rather than undergo genetic testing as a primary option.

Objective: To evaluate the association between maternal body mass index and obstetrical outcome in patients with a prior cesarean undergoing a trial of labor versus elective repeat cesarean., Study Design: A perinatal database between 1991 and 1997 was used to identify secundipara at term after a previous cesarean section. In different groups according to maternal body mass index, the rates of successful vaginal birth after caesarean, uterine scar separation, and other obstetrical outcomes were evaluated., Results: Of 8580 patients with a prior cesarean, 1862 (21.7%) underwent an elective repeat cesarean and 6718 (78.3%) underwent a trial of labor. Maternal body mass index correlated inversely with the rate of successful vaginal birth after caesarean but not with the rate of uterine scar separation. After adjustment for confounding factors including maternal age, birth weight, induction of labor, and preeclampsia, maternal body mass index remained associated with a lower rate of successful vaginal birth after cesarean., Conclusion: Maternal body mass index is an independent factor associated with a lower rate of successful vaginal birth after cesarean.

Objective: The purpose of this study was to evaluate the accuracy of the prenatal diagnosis of left isomerism and to assess possible diagnostic and prognostic markers., Methods: We conducted a retrospective review of all previously unpublished cases of left isomerism diagnosed in the prenatal and postnatal periods in 2 tertiary referral centers in Germany over 15 years., Results: Among 34 fetuses, 31 had a correct prenatal diagnosis of left isomerism; 31 had an interruption of the inferior vena cava with azygos continuation; 22 had different types of viscerocardiac heterotaxy; 13 had heart block; and 28 had cardiac defects, with a high prevalence of atrioventricular septal defects (n = 24), right outflow tract obstruction (n = 11), double-outlet right ventricles (n = 6), and anomalous pulmonary venous return (n = 6). Among the 34 cases, 9 underwent termination of pregnancy; 2 fetuses died in utero; 5 children died in the neonatal period; and 4 children died in infancy. Only the presence of heart block and hydrops was significantly correlated with nonsurvival (P < .05). Fourteen children survived, with a mean follow-up +/- SD of 2.9 +/- 2.6 years. Three survivors underwent single-ventricle palliation, and 1 had successful biventricular repair. Three children were awaiting cardiac repair. The remaining 7 children had minor or no associated cardiac defects and were doing well., Conclusions: Prenatal diagnosis of left isomerism is feasible, with high accuracy. Important diagnostic pointers are viscerocardiac heterotaxy, complex cardiac malformations, heart block, and interruption of the inferior vena cava. The mortality in fetuses and neonates is high in the presence of heart block and hydrops, whereas the cardiac defects influence the long-term outcome.

Objective: The purpose of this study was to characterize the effect of smoking on the incidence of various pregnancy complications., Study Design: A population-based retrospective analysis with a perinatal database of 170,254 singleton pregnancies was performed. The rate of pregnancy complications was calculated in 4 strata of smokers: Nonsmokers, 1 to 5 cigarettes per day, 6 to 10 cigarettes per day, and >10 cigarettes per day. Logistic regression was used to calculate odds ratios as measures of an association of smoking with various pregnancy complications after correction for confounding factors., Results: The mean age of the study population was 29 +/- 4.8 years. The odds ratio for preeclampsia was 0.64 (95 % CI, 0.59-0.70), for intrauterine growth restriction was 2.4 (95% CI, 2.34-2.53), and for preterm delivery was 1.2 (95% CI, 1.13-1.28)., Conclusion: Smoking decreased the incidence of preeclampsia in a dose-effect manner and was shown to increase the rate of intrauterine growth restriction and preterm delivery.

Objective: To assess the accuracy of fetal echocardiography in the prenatal diagnosis of cardiosplenic syndromes and the spectrum of associated anomalies., Methods: This was a retrospective survey of fetuses in our databases over a period of 10 years with postnatally confirmed prenatal diagnosis of cardiosplenic syndromes., Results: In 32 of 35 fetuses the prenatal diagnosis of cardiosplenic syndromes was confirmed postpartum. Twenty-two fetuses had left isomerism. Their main prenatal ultrasound features were interrupted inferior vena cava (n = 21), complete atrioventricular septal defect (n = 15), viscerocardiac heterotaxy (n = 15), persistent bradyarrhythmia (n = 12) and fetal hydrops or nuchal edema (n = 12). Twelve pregnancies were terminated, two fetuses were stillborn and eight infants survived. Ten fetuses had right isomerism. Their main sonographic features were juxtaposition of the descending aorta and inferior vena cava (n = 7), complete atrioventricular septal defect (n = 7), left persistent superior vena cava (n = 6) and viscerocardiac heterotaxy (n = 6). In this group there was one stillbirth, five infant deaths and four survivors. The overall survival rate and spectrum of other cardiac malformations were similar between the two groups. Prenatal diagnosis of other visceral features of cardiosplenic syndromes was inconsistent., Conclusion: Cardiosplenic syndromes can be diagnosed with high accuracy by prenatal sonography. A diagnosis of left isomerism should be strongly suggested in the presence of a combination of at least two of the following: (1) complete atrioventricular septal defect or other structural heart disease; (2) interruption of inferior vena cava with azygos continuation; (3) early fetal heart block; (4) viscerocardiac heterotaxy. Right isomerism should be suspected in the presence of a combination of at least two of the following: (1) structural heart disease, namely complete atrioventricular septal defect; (2) juxtaposition of inferior vena cava and descending aorta; (3) viscerocardiac heterotaxy., (Copyright 2003 ISUOG. Published by John Wiley & Sons, Ltd.)

We wanted to evaluate whether improvement in ultrasound equipment in the last 5 years altered our perception of the phases of placental separation during the third stage of labor. We also investigated the influence of active management on the third stage of labor after sonographically verified placental separation. Between January and November 2001, the third stage of labor was examined in 55 women at 37-41 weeks of gestation by color Doppler sonography. The duration of blood flow between the myometrium and the placenta, the latent phase, the detachment phase, and the expulsion phase were measured and compared with the corresponding values of an earlier cohort of 57 patients investigated between November 1994 and August 1995. In the later cohort, both the duration of maternal blood flow and the detachment phase were significantly longer than in the earlier cohort (33 s +/- 48 s vs 0 s, P<0.0001 and 56 s+/-45 s vs 37 s+/-21 s, P<0.01, respectively), whereas the latent phase was significantly shorter (101 s+/-87 s vs 213 s+/-180 s, P<0.0001). There was no statistically significant difference in the length of the expulsion phase or the third stage of labor. The later cohort showed a statistically significantly more frequent multiphasic placental detachment ( P<0.05). Improvement in ultrasound equipment resulted in an earlier detection of the onset of placental separation, leading to a shorter latent phase and consecutively increased duration of the detachment phase, whereas the total duration of the third stage of labor remained unchanged. Furthermore, increased sensitivity of Doppler sonography led to a longer visualization of blood flow between the myometrium and the placenta in the normal third stage of labor.

Congenital megalourethra is a rare disorder. We present an early case diagnosed in the first trimester. Prenatal ultrasound showed a megalourethra with a normal fetal bladder, hyperechogenic cystic right kidney and single umbilical artery. After termination of pregnancy, necropsy confirmed all sonographic findings and revealed other malformations (spina bifida occulta, anal atresia, tracheo-oesophageal fistula, brachydactylia) resulting in the diagnosis of VACTERL association. The prenatal diagnostician should seek histological examination firstly to confirm his findings and secondly to avoid missing associations and inherited malformations., (Copyright 2002 John Wiley & Sons, Ltd.)

The implementation of quality elements in research and development is a hot issue, still under discussion and development. In recent years much progress has been made in the development of effective proposals. However there are still problems and misunderstandings on how to apply quality assurance in research and development. This work clarifies these issues, mainly caused by the application of formal standards for quality assurance in R&D. It lists reasons for, and demonstrates benefits of, implementing quality elements in R&D and then offers detailed suggestions for addressing the most important issues without hampering the flexibility and creativity of R&D.

Objective: In animals and adult humans sustained supraventricular tachycardia leads to myocardial remodelling and dysfunction, persisting even after drug-induced cardioversion to sinus rhythm. This study was undertaken, to evaluate cardiac function in the human fetus by noninvasive determination of the degree of AV valve incompetence and venous blood flow, in order to enhance understanding of the pathophysiology of fetal supraventricular tachycardia. Furthermore, we wanted to determine the usefulness of these methods in the surveillance of these fetuses before and after drug-induced cardioversion., Study Design: Eleven fetuses with supraventricular tachycardia between 24 and 35 weeks of gestation were studied. AV valve regurgitation and venous Doppler waveforms of the inferior vena cava and ductus venosus were evaluated before and after conversion to sinus rhythm., Results: Three different groups of fetuses could be distinguished. The first group consisted of four fetuses with neither signs of hydrops nor AV valve incompetence. Venous indices normalized within one to four days (median 2.5 days) after conversion to sinus rhythm. The second group contained two fetuses with hydrops, but without AV valve incompetence. Their venous indices normalized at the day of conversion and 3 days later, respectively (median 1.5 days). The last group of five fetuses consisted of four fetuses with hydrops and AV valve regurgitation during supraventricular tachycardia. In one fetus with hydrops and supraventricular tachycardia the fetal heart rate was continuously decreased to a level of 160-190 beats/min under drug treatment, but no conversion to sinus rhythm occurred. The venous indices of these fetuses normalized within 12-42 days (median 27 days) after conversion., Conclusion: Our data suggest that in sustained fetal supraventricular tachycardia alterations of myocardial function similar to tachycardia-induced 'cardiomyopathy' occur. The severity of tachycardia-induced changes of cardiac function is reflected by the degree and persistence of AV valve incompetence, as well as by alterations of the venous blood flow pattern. Under clinical conditions, the latter can readily and well reproducibly be demonstrated by calculating the venous blood flow indices of the inferior vena cava and ductus venosus.