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Myelomeningocele is a common dysraphic defect leading to severe impairment throughout the patient's lifetime. Although surgical closure of this anomaly is usually performed in the early postnatal period, an estimated 330 cases of intrauterine repair have been performed in a few specialized centers worldwide. It was hoped prenatal intervention would improve the prognosis of affected patients, and preliminary findings suggest a reduced incidence of shunt-dependent hydrocephalus, as well as an improvement in hindbrain herniation. However, the expectations for improved neurological outcome have not been fulfilled and not all patients benefit from fetal surgery in the same way. Therefore, a multicenter randomized controlled trial was initiated in the USA to compare intrauterine with conventional postnatal care, in order to establish the procedure-related benefits and risks. The primary study endpoints include the need for shunt at 1 year of age, and fetal and infant mortality. No data from the trial will be published before the final analysis has been completed in 2008, and until then, the number of centers offering intrauterine MMC repair in the USA is limited to 3 in order to prevent the uncontrolled proliferation of new centers offering this procedure. In future, refined, risk-reduced surgical techniques and new treatment options for preterm labor and preterm rupture of the membranes are likely to reduce associated maternal and fetal risks and improve outcome, but further research will be needed. [ABSTRACT FROM AUTHOR]

The antigen-binding ability of each antibody clone selected by phage display is usually initially ranked by a screening ELISA using monovalent scFv antibody fragments. Further characterization often requires bivalent antibody molecules such as IgG or scFv-Fc fusions. To produce these, the V region encoding genes of selected hits have to be cloned into a mammalian expression vector and analyzed as a bivalent molecule, requiring a laborious cloning procedure. We established a high-throughput procedure allowing rapid screening of candidates in bivalent formats. This protocol allows for the parallelized cloning of all selected antibody fragments into a mammalian expression vector in the 96-well plate format. The bivalent antibody molecules can then be produced and purified in 96-well plates for further analysis in microtiter plate assays., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The most common and robust in vitro technology to generate monoclonal human antibodies is phage display. This technology is a widely used and powerful key technology for recombinant antibody selection. Phage display-derived antibodies are used as research tools, in diagnostic assays, and by 2022, 14 phage display-derived therapeutic antibodies were approved. In this review, we describe a fast high-throughput antibody (scFv) selection procedure in 96-well microtiter plates. The given detailed protocol allows the antibody selection ("panning"), screening, and identification of monoclonal antibodies in less than 2 weeks. Furthermore, we describe an on-rate panning approach for the selection of monoclonal antibodies with fast on-rates., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Virus-like particles (VLPs) resemble authentic virus while not containing any genomic information. Here, we present a fast and powerful method for the production of SARS-CoV-2 VLP in insect cells and the application of these VLPs to evaluate the inhibition capacity of monoclonal antibodies and sera of vaccinated donors. Our method avoids the baculovirus-based approaches commonly used in insect cells by employing direct plasmid transfection to co-express SARS-CoV-2 envelope, membrane, and spike protein that self-assemble into VLPs. After optimization of the expression plasmids and vector ratios, VLPs with an ~145 nm diameter and the typical "Corona" aura were obtained, as confirmed by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Fusion of the membrane protein to GFP allowed direct quantification of binding inhibition to angiotensin II-converting enzyme 2 (ACE2) on cells by therapeutic antibody candidates or sera from vaccinated individuals. Neither VLP purification nor fluorescent labeling by secondary antibodies are required to perform these flow cytometric assays.

One of the most widely used epitope tags is the myc-tag, recognized by the anti-c-Myc hybridoma antibody Myc1-9E10. Combining error-prone PCR, DNA shuffling and phage display, we generated an anti-c-Myc antibody variant (Hyper-Myc) with monovalent affinity improved to 18 nM and thermal stability increased by 37%. Quantification of capillary immunoblots and by flow cytometry demonstrated improved antigen detection by Hyper-Myc. Further, three different species variants of this antibody were generated to allow the use of either anti-human, anti-mouse or anti-rabbit Fc secondary antibodies for detection. We characterized the specificity of both antibodies in depth: individual amino acid exchange mapping demonstrated that the recognized epitope was not changed by the in vitro evolution process. A laser printed array of 29,127 different epitopes representing all human linear B-cell epitopes of the Immune Epitope Database allowing to chart unwanted reactivities with mimotopes showed these to be very low for both antibodies and not increased for Hyper-Myc despite its improved affinity. The very low background reactivity of Hyper-Myc was confirmed by staining of myc-tag transgenic zebrafish whole mounts. Hyper-Myc retains the very high specificity of Myc1-9E10 while allowing myc-tag detection at lower concentrations and with either anti-mouse, anti-rabbit or anti human secondary antibodies., (© 2022 Giulio Russo et al., published by De Gruyter, Berlin/Boston.)

Generation of sequence defined antibodies from universal libraries by phage display has been established over the past three decades as a robust method to cope with the increasing market demand in therapy, diagnostics and research. For applications requiring the bivalent antigen binding and an Fc part for detection, phage display generated single chain Fv (scFv) antibody fragments can rapidly be genetically fused to the Fc moiety of an IgG for the production in eukaryotic cells of antibodies with IgG-like properties. In contrast to conversion of scFv into IgG format, the conversion to scFv-Fc requires only a single cloning step, and provides significantly higher yields in transient cell culture production than IgG. ScFv-Fcs can be effective as neutralizing antibodies in vivo against a panel of pathogens and toxins. However, different scFv fragments are more heterologous in respect of stability than Fab fragments. While some scFv fragments can be made extremely stable, this may change due to few mutations, and is not predictable from the sequence of a newly selected antibody. To mitigate the necessity to assess the stability for every scFv-Fc antibody, we developed a generic lyophilization protocol to improve their shelf life. We compared long-term stability and binding activity of phage display-derived antibodies in the scFv-Fc and IgG format, either stored in liquid or lyophilized state. Conversion of scFv-Fcs into the full IgG format reduced protein degradation and aggregation, but in some cases compromised binding activity. Comparably to IgG conversion, lyophilization of scFv-Fc resulted in the preservation of the antibodies' initial properties after storage, without any drop in affinity for any of the tested antibody clones., Competing Interests: GR, EW, and SD are co-founders and shareholders of Abcalis GmbH. SD and MH are co-founders and shareholders of mAb-factory GmbH, YUMAB GmbH and NordenVaccines GmbH. DM is co-founder and shareholder of mAb-factory GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schneider, Kirmann, Wenzel, Grosch, Polten, Meier, Becker, Matejtschuk, Hust, Russo and Dübel.)

The novel betacoronavirus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) causes a form of severe pneumonia disease called coronavirus disease 2019 (COVID-19). To develop human neutralizing anti-SARS-CoV-2 antibodies, antibody gene libraries from convalescent COVID-19 patients were constructed and recombinant antibody fragments (scFv) against the receptor-binding domain (RBD) of the spike protein were selected by phage display. The antibody STE90-C11 shows a subnanometer IC 50 in a plaque-based live SARS-CoV-2 neutralization assay. The in vivo efficacy of the antibody is demonstrated in the Syrian hamster and in the human angiotensin-converting enzyme 2 (hACE2) mice model. The crystal structure of STE90-C11 Fab in complex with SARS-CoV-2-RBD is solved at 2.0 Å resolution showing that the antibody binds at the same region as ACE2 to RBD. The binding and inhibition of STE90-C11 is not blocked by many known emerging RBD mutations. STE90-C11-derived human IgG1 with FcγR-silenced Fc (COR-101) is undergoing Phase Ib/II clinical trials for the treatment of moderate to severe COVID-19., Competing Interests: Declaration of interests F.B., D.M., N.L., S. Steinke, P.A.H., R.B., M.R., K.-T.S., K.D.R.R., S.Z.-E., M.B., V.F., S.D., M. Schubert, and M.H. are inventors on a patent application on blocking antibodies against SARS-CoV-2. A.H., A.F., and T.S. are officers of CORAT Therapeutics GmbH, a company founded by YUMAB GmbH for the clinical and regulatory development of STE90-C11 (development name COR-101) (ClinicalTrials.gov ID: NCT04674566 for safety and efficacy of COR-101 in hospitalized patients with moderate to severe COVID-19). A.H. is a shareholder of CORAT Therapeutics GmbH. S.D. and M.H. are advisors to Corat Therapeutics GmbH. A.F., T.S., S.D., and M.H. are shareholders of YUMAB GmbH., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Antibodies are essential molecules for diagnosis and treatment of diseases caused by pathogens and their toxins. Antibodies were integrated in our medical repertoire against infectious diseases more than hundred years ago by using animal sera to treat tetanus and diphtheria. In these days, most developed therapeutic antibodies target cancer or autoimmune diseases. The COVID-19 pandemic was a reminder about the importance of antibodies for therapy against infectious diseases. While monoclonal antibodies could be generated by hybridoma technology since the 70ies of the former century, nowadays antibody phage display, among other display technologies, is robustly established to discover new human monoclonal antibodies. Phage display is an in vitro technology which confers the potential for generating antibodies from universal libraries against any conceivable molecule of sufficient size and omits the limitations of the immune systems. If convalescent patients or immunized/infected animals are available, it is possible to construct immune phage display libraries to select in vivo affinity-matured antibodies. A further advantage is the availability of the DNA sequence encoding the phage displayed antibody fragment, which is packaged in the phage particles. Therefore, the selected antibody fragments can be rapidly further engineered in any needed antibody format according to the requirements of the final application. In this review, we present an overview of phage display derived recombinant antibodies against bacterial, viral and eukaryotic pathogens, as well as microbial toxins, intended for diagnostic and therapeutic applications., Competing Interests: EW, GR, and SD are shareholders of Abcalis GmbH. AF, TS, SD, and MH are shareholders of YUMAB GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Roth, Wenzel, Ruschig, Steinke, Langreder, Heine, Schneider, Ballmann, Fühner, Kuhn, Schirrmann, Frenzel, Dübel, Schubert, Moreira, Bertoglio, Russo and Hust.)

COVID-19 is a severe acute respiratory disease caused by SARS-CoV-2, a new recently emerged sarbecovirus. This virus uses the human ACE2 enzyme as receptor for cell entry, recognizing it with the receptor binding domain (RBD) of the S1 subunit of the viral spike protein. We present the use of phage display to select anti-SARS-CoV-2 spike antibodies from the human naïve antibody gene libraries HAL9/10 and subsequent identification of 309 unique fully human antibodies against S1. 17 antibodies are binding to the RBD, showing inhibition of spike binding to cells expressing ACE2 as scFv-Fc and neutralize active SARS-CoV-2 virus infection of VeroE6 cells. The antibody STE73-2E9 is showing neutralization of active SARS-CoV-2 as IgG and is binding to the ACE2-RBD interface. Thus, universal libraries from healthy human donors offer the advantage that antibodies can be generated quickly and independent from the availability of material from recovering patients in a pandemic situation.

Background: Phase-rectified signal averaging, an innovative signal processing technique, can be used to investigate quasi-periodic oscillations in noisy, nonstationary signals that are obtained from fetal heart rate. Phase-rectified signal averaging is currently the best method to predict survival after myocardial infarction in adult cardiology. Application of this method to fetal medicine has established significantly better identification than with short-term variation by computerized cardiotocography of growth-restricted fetuses., Objective: The aim of this study was to determine the longitudinal progression of phase-rectified signal averaging indices in severely growth-restricted human fetuses and the prognostic accuracy of the technique in relation to perinatal and neurologic outcome., Study Design: Raw data from cardiotocography monitoring of 279 human fetuses were obtained from 8 centers that took part in the multicenter European "TRUFFLE" trial on optimal timing of delivery in fetal growth restriction. Average acceleration and deceleration capacities were calculated by phase-rectified signal averaging to establish progression from 5 days to 1 day before delivery and were compared with short-term variation progression. The receiver operating characteristic curves of average acceleration and deceleration capacities and short-term variation were calculated and compared between techniques for short- and intermediate-term outcome., Results: Average acceleration and deceleration capacities and short-term variation showed a progressive decrease in their diagnostic indices of fetal health from the first examination 5 days before delivery to 1 day before delivery. However, this decrease was significant 3 days before delivery for average acceleration and deceleration capacities, but 2 days before delivery for short-term variation. Compared with analysis of changes in short-term variation, analysis of (delta) average acceleration and deceleration capacities better predicted values of Apgar scores <7 and antenatal death (area under the curve for prediction of antenatal death: delta average acceleration capacity, 0.62 [confidence interval, 0.19-1.0]; delta short-term variation, 0.54 [confidence interval, 0.13-0.97]; P=.006; area under the curve for prediction Apgar <7: average deceleration capacity <24 hours before delivery, 0.64 [confidence interval, 0.52-0.76]; short-term variation <24 hours before delivery, 0.53 [confidence interval, 0.40-0.65]; P=.015). Neither phase-rectified signal averaging indices nor short-term variation showed predictive power for developmental disability at 2 years of age (Bayley developmental quotient, <95 or <85)., Conclusion: The phase-rectified signal averaging method seems to be at least as good as short-term variation to monitor progressive deterioration of severely growth-restricted fetuses. Our findings suggest that for short-term outcomes such as Apgar score, phase-rectified signal averaging indices could be an even better test than short-term variation. Overall, our findings confirm the possible value of prospective trials based on phase-rectified signal averaging indices of autonomic nervous system of severely growth-restricted fetuses., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The 2011 guidelines of the European Society of Cardiology (ESC) on the management of cardiovascular diseases during pregnancy define the maternal predictors for neonatal complications. The aim of this study was to determine whether these are associated with an increased number of miscarriages/stillbirths and terminations of pregnancy (TOPs) also in patients with congenital heart defects (CHD)., Methods and results: The 634 women from Germany, Hungary and Japan were surveyed concerning the issues of sexuality and reproductive health, as well as their general life situation and medical care. 25% of the recorded pregnancies in women with CHD resulted in miscarriage, stillbirth or TOP. Affecting 16.8% of all recorded pregnancies, miscarriages or stillbirths occurred more frequently than in the general population and more than previously recorded for patients with CHD. TOP occurred in 8% of the surveyed pregnancies. Underlying maternal predictors for neonatal events had an influence on the number of TOP; among those with underlying predictors, TOP was recorded 3-fold more than in those without such predictors (15.6% vs. 5.5%). Remarkably, a significant deficit regarding the level of information on potential pregnancy-associated risks was observed in all 3 participating countries., Conclusions: Pregnant women with CHD should always be treated and counseled individually by cardiologists, gynecologists, obstetricians and anesthetists with appropriate expert knowledge. (Circ J 2016; 80: 1846-1851).

Aims: For women with congenital heart defects (CHD), pregnancy may pose a health risk. Sexually active women with CHD without the desire for own children or for whom pregnancy would imply considerable health risks require adequate counselling regarding appropriate contraception. This study gathers data on the contraceptive behaviour of women with CHD from three different cultural regions., Methods and Results: 634 women with CHD from Germany, Hungary and Japan were surveyed regarding contraception and contraceptive methods (CM) used. The patients were divided into groups according to different criteria such as pregnancy associated cardiovascular risk or "safety" of the contraceptive methods used. 59% of the study participants had already gained experience with CM. The average age at the first time of use was 18.4 years; the German patients were significantly younger at the first time of using a CM than those from Hungary and Japan. Overall the condom was the method used the most (38%), followed by oral contraceptives (30%) and coitus interruptus (11%). The range of CM used in Japan was much smaller than that in Germany or Hungary. Unsafe contraceptives were currently, or had previously been used, by 29% of the surveyed patients (Germany: 25%, Hungary: 37%, Japan: 32%)., Conclusion: Most women with CHD use CM. There are differences between the participating countries. Adequate contraceptive counselling of women with CHD requires considering the individual characteristics of each patient, including potential contraindications. For choosing an appropriate CM, both the methods' "safety", as well as the maternal cardiovascular risk, are important., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Extracorporeal membrane oxygenation (ECMO) is increasingly used for the management of acute severe cardiac and respiratory failure. One of the indications is acute respiratory distress syndrome (ARDS) for which, in some severe cases, ECMO represents the only possibility to save lives. We report on the successful long-term use of ECMO in a postpartum patient with recurrent pulmonary decompensation after peripartum uterine rupture with extensive blood loss.

Purpose: The aim was to establish an official interdisciplinary guideline, published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). The guideline was developed for use in German-speaking countries. In addition to the Germany Society of Gynecology and Obstetrics, the guideline has also been approved by the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). The aim was to standardize diagnostic procedures and the management of gestational and non-gestational trophoblastic disease in accordance with the principles of evidence-based medicine, drawing on the current literature and the experience of the colleagues involved in compiling the guideline. Methods: This s2k guideline represents the consensus of a representative panel of experts with a range of different professional backgrounds commissioned by the DGGG. Following a review of the international literature and international guidelines on trophoblastic tumors, a structural consensus was achieved in a formalized, multi-step procedure. This was done using uniform definitions, objective assessments, and standardized management protocols. Recommendations: The recommendations of the guideline cover the epidemiology, classification and staging of trophoblastic tumors; the measurement of human chorionic gonadotropin (hCG) levels in serum, and the diagnosis, management, and follow-up of villous trophoblastic tumors (e.g., partial mole, hydatidiform mole, invasive mole) and non-villous trophoblastic tumors (placental site nodule, exaggerated placental site, placental site tumor, epitheloid trophoblastic tumor, and choriocarcinoma).

The aim of this study was to identify which operation technique [total cervical occlusion (TMV), cerclage (C) or combination of both (TMV+C)] would lead to the greatest pregnancy prolongation in 3 different collectives of patients at risk (history of preterm birth, cervical insufficiency, prolapsing membranes). In this retrospective data collection, 200 cervical occlusions performed between 1997 and 2010 were analysed. In patients with a history of preterm birth/stillbirth (n=80) a prophylactic TMV increased the lifebirth rate from 35% without TMV to 95% with TMV (p<0.001). The risk diminuation after TMV was - 60% for stillbirth (p<0.001) and - 30% for preterm birth (p=0.01). In this subcollective the TMV seemed to be more effective in pregnancy prolongation (days) than C (139 vs. 113 days), however the combination of both (C+TMV) did not add much benefit (142 days). In patients with cervical insuffiency (n=86) the pregnancy could be prolonged by 82 (C), 79 (TMV) und 109 days (C+TMV) (p=0.003-0.017) and in patients with membrane prolaps (n=34) by 63 (C), 61 (TMV) und 76 (C+TMV) days. According to present data, the combination of cerclage and TMV has the highest benefit on pregnancy prolongation. This analysis should provide a basis for randomised controlled studies on this topic., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: No consensus exists for the best way to monitor and when to trigger delivery in mothers of babies with fetal growth restriction. We aimed to assess whether changes in the fetal ductus venosus Doppler waveform (DV) could be used as indications for delivery instead of cardiotocography short-term variation (STV)., Methods: In this prospective, European multicentre, unblinded, randomised study, we included women with singleton fetuses at 26-32 weeks of gestation who had very preterm fetal growth restriction (ie, low abdominal circumference [<10th percentile] and a high umbilical artery Doppler pulsatility index [>95th percentile]). We randomly allocated women 1:1:1, with randomly sized blocks and stratified by participating centre and gestational age (<29 weeks vs ≥29 weeks), to three timing of delivery plans, which differed according to antenatal monitoring strategies: reduced cardiotocograph fetal heart rate STV (CTG STV), early DV changes (pulsatility index >95th percentile; DV p95), or late DV changes (A wave [the deflection within the venous waveform signifying atrial contraction] at or below baseline; DV no A). The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley III developmental score of less than 85, at 2 years of age. We assessed outcomes in surviving infants with known outcomes at 2 years. We did an intention to treat study for all participants for whom we had data. Safety outcomes were deaths in utero and neonatal deaths and were assessed in all randomly allocated women. This study is registered with ISRCTN, number 56204499., Findings: Between Jan 1, 2005 and Oct 1, 2010, 503 of 542 eligible women were randomly allocated to monitoring groups (166 to CTG STV, 167 to DV p95, and 170 to DV no A). The median gestational age at delivery was 30·7 weeks (IQR 29·1-32·1) and mean birthweight was 1019 g (SD 322). The proportion of infants surviving without neuroimpairment did not differ between the CTG STV (111 [77%] of 144 infants with known outcome), DV p95 (119 [84%] of 142), and DV no A (133 [85%] of 157) groups (ptrend=0·09). 12 fetuses (2%) died in utero and 27 (6%) neonatal deaths occurred. Of survivors, more infants where women were randomly assigned to delivery according to late ductus changes (133 [95%] of 140, 95%, 95% CI 90-98) were free of neuroimpairment when compared with those randomly assigned to CTG (111 [85%] of 131, 95% CI 78-90; p=0.005), but this was accompanied by a non-significant increase in perinatal and infant mortality., Interpretation: Although the difference in the proportion of infants surviving without neuroimpairment was non-significant at the primary endpoint, timing of delivery based on the study protocol using late changes in the DV waveform might produce an improvement in developmental outcomes at 2 years of age., Funding: ZonMw, The Netherlands and Dr Hans Ludwig Geisenhofer Foundation, Germany., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We examined perceptions of spirituality and meaning among 192 employees (77% female) from a non-profit organization in a mid-sized Midwestern city in the United States. We hypothesized that employees' values related to workplace spirituality would be positively related to various measures of job satisfaction and general meaning in life. We also examined employees' perceptions of the fit of their co-workers' values with the agency mission and predicted that these perceptions would act as a moderator of the relationship between employees' workplace spirituality and job satisfaction. Our hypotheses were generally supported. Spirituality predicted work contributing to the meaning of life and various facets of job satisfaction. Implications of the importance of employees' perceptions of organizational fit related to spirituality and the perceived fit of co-workers' values with the organizational mission are discussed.

Aim: The aim of this study was to develop new national standards for birth weight, length, head circumference, and weight for length for newborn twins based on the German perinatal survey of 2007-2011. We also assessed trends in anthropometric measurements by comparing these new percentile values with the percentile values of 1990-1994., Material and Methods: Perinatal survey data of 110,313 newborn twins from all the states of Germany collected in the years 2007-2011 were kindly provided by the AQUA Institute in Göttingen, Germany. Sex specific percentile values were calculated using cumulative frequencies. Percentile values at birth were computed for the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles for 21-40 completed weeks of gestation. Percentile curves and tabulated values for the years 2007-2011 were compared with the published values of 1990-1994., Results and Discussion: The new percentile curves (2007-2011) closely resemble the previous ones (1990-1994). Small differences can nonetheless be found. For example, for birth weight the new values for the 10th percentile are a little higher., Conclusions: We recommend using the new percentile values instead of the old ones., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim: The aim of this study was to derive percentile values for birth weight, length, head circumference, and weight for length for singleton neonates based on the German perinatal survey of 2007-2011 (using data from all 16 states of Germany). We also compared these new percentile values with the percentile values of 1995-2000 that so far have been considered standard values., Material and Methods: Data of 3 187 920 singleton neonates from the German perinatal survey of the years 2007-2011 were kindly provided to us by the AQUA Institute in Göttingen, Germany. Sex specific percentile values were calculated using cumulative frequencies. Percentile values at birth were computed for the 3(rd), 10(th), 25(th), 50(th), 75(th), 90(th), and 97(th) percentiles for 21-43 completed weeks of gestation. Percentile curves and tabulated values for the years 2007-2011 were compared with the published values of 1995-2000., Results and Discussion: Overall the new percentile curves closely resemble the previous ones. Minimal differences can be found for the 10(th) percentile and generally for early weeks of gestation. Values for the 10(th) percentile in the 2007-2011 dataset are somewhat higher than values of 1995-2000 for birth weight, length, and weight for length., Conclusions: We recommend the use of these new percentile values instead of the old ones., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Maternal obesity and gestational diabetes mellitus (GDM) may independently influence offspring fat mass and metabolic disease susceptibility. In this pilot study, body composition and fat distribution in offspring from obese women with and without GDM and lean women were assessed within the 1st year of life, and maternal and newborn plasma factors were related to offspring adipose tissue distribution., Methods: Serum and plasma samples from pregnant obese women with (n = 16) or without (n = 13) GDM and normoglycemic lean women (n = 15) at 3rd trimester and offspring cord plasma were used for analyzing lipid profiles, insulin and adipokine levels. At week-1 and 6, month-4 and year-1, offspring anthropometrics and skinfold thickness (SFT) were measured and abdominal subcutaneous (SCA) and preperitoneal adipose tissue (PPA) were determined by ultrasonography., Results: Cord insulin was significantly increased in the GDM group, whereas levels of cord leptin, total and high molecular weight (HMW) adiponectin were similar between the groups. Neonates of the GDM group showed significantly higher SFT and fat mass until week-6 and significantly increased SCA at week-1 compared to the lean group that persisted as strong trend at week-6. Interestingly, PPA in neonates of the GDM group was significantly elevated at week-1 compared to both the lean and obese group. At month-4 and year-1, significant differences in adipose tissue growth between the groups were not observed. Multiple linear regression analyses revealed that cord insulin levels are independently related to neonatal PPA that showed significant relation to PPA development at year-1. Maternal fasted C-peptide and HMW adiponectin levels at 3rd trimester emerged to be determinants for PPA at week-1., Conclusion: Maternal pregravid obesity combined with GDM leads to newborn hyperinsulinemia and increased offspring fat mass until week-6, whereas pregravid obesity without GDM does not. This strongly suggests the pivotal role of GDM in the adverse offspring outcome. Maternal C-peptide and HMW adiponectin levels in pregnancy emerge to be predictive for elevated PPA in newborns and might be indicative for the obesity risk at later life. Altogether, the findings from our pilot study warrant evaluation in long-term studies., Trial Registration: German Clinical Trials Register DRKS00004370.

Background: The number of women with congenital heart disease reaching reproductive age has increased due to therapeutic advances. The aim of this study was to examine obstetric and cardiac problems during pregnancy after Mustard/Senning repair for transposition of the great arteries., Methods and Results: Sixty pregnancies in 34 women from 3 centers were studied. The women were interviewed, and their records reviewed for clinical status and diagnostic evaluation. Age range was 16-34 years during first pregnancy, and all were in a low functional class. There were 11 miscarriages and 5 abortions. Of 44 successful pregnancies, 20 were vaginal deliveries and 24, cesarean sections. A total of 25% were delivered prematurely. Thirteen babies had birth weight <2,500g. Deterioration in functional class occurred in 7 pregnancies, without recovery in 5. Deterioration in systolic function occurred in 4 of 44 echocardiographically documented pregnancies, without recovery in 75%. In 2 women resuscitation was necessary during delivery, in 1, supraventricular tachycardia occurred during labor., Conclusions: Pregnancy is usually well-tolerated, but outcome is unforeseeable and life-threatening problems can occur. These women belong in cardiac care conducted by experienced congenital cardiologists, who systematically check for typical residua. The pregnancy should be planned and gynecologists/obstetricians with special expertise integrated into the consultations. During delivery a congenital cardiologist, and an anesthetist experienced in congenital cardiology, should be present for possible severe cardiac events.

Background and Aim: We have previously presented analyses of data obtained from the German Perinatal Survey for the years 1995-1997. Here we present an analysis of data from the years 2007-2011 and compare the data to the previous data from the 1990s. Material and Methods: For the years 1995-1997, the data on 1 815 318 singleton pregnancies were provided by the Chambers of Physicians of all the states of Germany except Baden-Württemberg. For the years 2007-2011, the data on 3 187 920 singleton pregnancies from the German Perinatal Survey (all states of Germany) were obtained from the AQUA Institute in Göttingen, Germany. SPSS was used for data analysis. Plausibility checks were performed on the data. Results: Mean maternal age has increased over the years, from 28.7 years in 1995 to 30.2 years in 2011. We observed a decrease in smoking. While not all cases included data on maternal smoking after the pregnancy was known, when the cases with data on smoking were analysed, in 1995-1997 23.5 % of pregnant women were smokers compared to 11.2 % smokers in 2007-2011. Maternal body mass index (BMI) also changed; 8.2 % of women were obese (BMI: 30-40 kg/m 2 ), while 13.0 % were obese in 2011. In 1995, 0.6 % of women were morbidly obese (BMI ≥ 40 kg/m 2 ) compared to 1.8 % of women in 2011. The mean maternal body weight at the time of the first obstetric consultation also increased from 65.9 kg in 1995 to 68.7 kg in 2011. Conclusions: While the decrease in the number of women smoking over time is clearly a positive development, increasing maternal age and obesity present challenges in clinical practice.

Background and Aim: We have previously analysed neonatal characteristics and duration of pregnancy in Germany based on data from the German Perinatal Survey of 1995-1997. Here we describe neonatal characteristics and duration of pregnancy based on the German Perinatal Survey of 2007-2011., Material and Methods: We had been provided with data from the German Perinatal Survey of 1995-1997 by the chambers of physicians of all the states of Germany except Baden-Württemberg (1 815 318 singleton neonates). We were also provided with access to the perinatal survey data of 2007-2011 by the AQUA Institute in Göttingen, Germany (3 187 920 singleton neonates). We investigated regional differences within Germany and also compared the 2 periods of time. We used the computer programme SPSS for data analysis and performed plausibility checks on the survey data., Results: Comparing the states of Germany, we found that birth weight was largest for neonates born in Schleswig-Holstein (3 407 g) and Mecklenburg-Western Pomerania (3 392 g); the lowest mean birth weight was observed in the Saarland (3 283 g). Preterm birth rate varied between 6.3% (Saxony) and 8.1% (Bremen, Saarland). Comparing 1995-1997 vs. 2007-2011, deliveries after 37 and 38 weeks of gestation were more common and deliveries after 39 and more weeks of gestation were less common in the later period of time., Conclusions: Regional differences in the anthropometric characteristics of neonates exist between the states of Germany. The proportion of deliveries after 39 and more weeks of gestation has decreased., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: Few data exist for counseling and perinatal management of women after an antenatal diagnosis of early-onset fetal growth restriction. Yet, the consequences of preterm delivery and its attendant morbidity for both mother and baby are far reaching. The objective of this study was to describe perinatal morbidity and mortality following early-onset fetal growth restriction based on time of antenatal diagnosis and delivery., Methods: We report cohort outcomes for a prospective multicenter randomized management study of fetal growth restriction (Trial of Randomized Umbilical and Fetal Flow in Europe (TRUFFLE)) performed in 20 European perinatal centers between 2005 and 2010. Women with a singleton fetus at 26-32 weeks of gestation, with abdominal circumference < 10(th) percentile and umbilical artery Doppler pulsatility index > 95(th) percentile, were recruited. The main outcome measure was a composite of fetal or neonatal death or severe morbidity: survival to discharge with severe brain injury, bronchopulmonary dysplasia, proven neonatal sepsis or necrotizing enterocolitis., Results: Five-hundred and three of 542 eligible women formed the study group. Mean ± SD gestational age at diagnosis was 29 ± 1.6 weeks and mean ± SD estimated fetal weight was 881 ± 217 g; 12 (2.4%) babies died in utero. Gestational age at delivery was 30.7 ± 2.3 weeks, and birth weight was 1013 ± 321 g. Overall, 81% of deliveries were indicated by fetal condition and 97% were by Cesarean section. Of 491 liveborn babies, outcomes were available for 490 amongst whom there were 27 (5.5%) deaths and 118 (24%) babies suffered severe morbidity. These babies were smaller at birth (867 ± 251 g) and born earlier (29.6 ± 2.0 weeks). Death and severe morbidity were significantly related to gestational age, both at study entry and delivery and also with the presence of maternal hypertensive morbidity. The median time to delivery was 13 days for women without hypertension, 8 days for those with gestational hypertension, 4 days for pre-eclampsia and 3 days for HELLP syndrome., Conclusions: Fetal outcome in this study was better than expected from contemporary reports: perinatal death was uncommon (8%) and 70% survived without severe neonatal morbidity. The intervals to delivery, death and severe morbidity were related to the presence and severity of maternal hypertensive conditions., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Aim. There is no consensus about the normal fetal heart rate. Current international guidelines recommend for the normal fetal heart rate (FHR) baseline different ranges of 110 to 150 beats per minute (bpm) or 110 to 160 bpm. We started with a precise definition of "normality" and performed a retrospective computerized analysis of electronically recorded FHR tracings. Methods. We analyzed all recorded cardiotocography tracings of singleton pregnancies in three German medical centers from 2000 to 2007 and identified 78,852 tracings of sufficient quality. For each tracing, the baseline FHR was extracted by eliminating accelerations/decelerations and averaging based on the "delayed moving windows" algorithm. After analyzing 40% of the dataset as "training set" from one hospital generating a hypothetical normal baseline range, evaluation of external validity on the other 60% of the data was performed using data from later years in the same hospital and externally using data from the two other hospitals. Results. Based on the training data set, the "best" FHR range was 115 or 120 to 160 bpm. Validation in all three data sets identified 120 to 160 bpm as the correct symmetric "normal range". FHR decreases slightly during gestation. Conclusions. Normal ranges for FHR are 120 to 160 bpm. Many international guidelines define ranges of 110 to 160 bpm which seem to be safe in daily practice. However, further studies should confirm that such asymmetric alarm limits are safe, with a particular focus on the lower bound, and should give insights about how to show and further improve the usefulness of the widely used practice of CTG monitoring.

This study examines the quantitative changes in the somatic classification according to birth weight and duration of pregnancy of German neonates when maternal height is considered (5 maternal height groups). Our calculations were performed using data of 319 884 girls born in 2010. Overall, about 6% (18 792 girls) are classified differently (more appropriately) when group-specific norm values were used., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Aim: The classification of weight gain during pregnancy and the somatic classification of neonates according to birth weight and duration of pregnancy can be done using percentile values. We aimed to compare such classifications using percentiles of the overall study population with classifications using percentiles that were calculated taking account of maternal height and weight. Material and Methods: Using data from the German Perinatal Survey (1995-2000, over 2.2 million singleton pregnancies) we classified weight gain during pregnancy as low (< 10th percentile), high (> 90th percentile), or medium (10th-90th percentile). Neonates were classified by birth weight as small for gestational age (SGA, < 10th percentile), large for gestational age (LGA, > 90th percentile), or appropriate for gestational age (AGA, 10th-90th percentile). Classifications were performed for 12 groups of women and their neonates formed according to maternal height and weight, either with the percentiles calculated from the total study population or with group-specific percentiles. Results: Using percentiles of the total study population there was large variability between the 12 groups in the proportions with low and high weight gain and in the proportions of SGA and LGA neonates. The variability was much lower when group-specific percentiles were used. Conclusions: Classifications of maternal weight gain during pregnancy and birth weight differ substantially, depending on whether percentiles calculated from the total study population or group-specific percentiles are used. The impact of using percentiles that take account of maternal anthropometric parameters for the medical care and health of neonates needs to be elucidated in future research.

Background: We have previously described the prevalence in pregnancy of hypertension, proteinuria, oedema and preeclampsia/eclampsia according to maternal body mass index (BMI) and smoking status. We found that these disorders were less frequent among smoking women. To investigate whether this relationship is causal or a chance finding, we here present an analysis according to BMI and smoking specified according to the number of cigarettes consumed per day., Materials and Methods: Data were from the German Perinatal Survey of 1998-2000. We classified women by BMI as underweight (BMI<18.5 kg/m2), normal weight (BMI 18.5-24.99 kg/m2), overweight (25.0-29.99 kg/m2), or obese (BMI≥30 kg/m2). Smoking was categorised as being a non-smoker or smoking 1-7, 8-14 or ≥ 15 cigarettes per day. Datasets from 433 669 singleton pregnancies with information on maternal BMI and smoking were included in the analysis., Results: In all BMI categories hypertension, moderate to severe oedema, and preeclampsia/eclampsia became less prevalent with increasing maternal cigarette consumption., Conclusions: Dose-dependence was not convincing for proteinuria.Dose-dependence in the relationship between smoking and hypertensive disorders of pregnancy argues against a chance finding and for a causal relationship., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To study fetal heart rate (FHR), its short term variability (STV), average acceleration capacity (AAC), and average deceleration capacity (ADC) throughout uncomplicated gestation, and to perform a preliminary comparison of these FHR parameters between small-for dates (SFD) and control fetuses., Methods: Prospective observational study of 7 h FHR-recordings obtained with a fetal-ECG monitor in the second half of uncomplicated pregnancies (n = 90) and pregnancies complicated by fetal SFD (n = 30). FHR and STV were calculated according to established analysis. True beat-to-beat FHR, recorded at 1 ms accuracy, was used to calculate AAC and ADC using Phase Rectified Signal Averaging (PRSA). Mean values of FHR, STV, AAC, and ADC derived from recordings in SFD fetuses were compared with the reference curves., Results: Compared with the control group the mean z-scores for STV, AAC, and ADC in SFD fetuses were lower by 1.0 SD, 1.5 SD, and 1.7 SD, respectively (p < 0.0001 for all comparisons). In SFD fetuses, both the AAC and ADC z-scores were lower than the STV z-scores (p < 0.02 and p < 0.002, respectively)., Conclusions: Analysis of the AAC and ADC as recorded with a high resolution fECG recorder may differentiate better between normal and SFD fetuses than STV.

Objective: This study aims to compare average acceleration capacity (AAC), a new parameter to assess the dynamic capacity of the fetal autonomous nervous system, and short term variation (STV) in fetuses affected by intrauterine growth restriction (IUGR) and healthy fetuses., Methods: A prospective observational study was performed, including 39 women with IUGR singleton pregnancies (estimated fetal weight <10th percentile and umbilical artery resistance index >95th percentile) and 43 healthy control pregnancies matched according to gestational age at recording. Ultrasound biometries and Doppler examination were performed for identification of IUGR and control fetuses, with subsequent analysis of fetal heart rate, resulting in STV and AAC. Follow-up for IUGR and control pregnancies was done, with perinatal outcome variables recorded., Results: AAC [IUGR mean value 2.0 bpm (interquartile range = 1.6-2.1), control 2.7 bpm (2.6-3.0)] differentiates better than STV [IUGR 7.4 ms (5.3-8.9), control 10.9 ms (9.2-12.7)] between IUGR and control. The area under the curve for AAC is 97 % [95% CI = (0.95-1.0)], for STV 85 % (CI = 0.76-0.93; p < 0.01). Positive predictive value for STV is 77% and negative predictive value is 81%. For AAC both positive and negative predictive values are 90%., Conclusions: AAC shows an improvement to discriminate between normal and compromised fetuses at a single moment in time, in comparison with STV.

Objectives: This study reports on current information sources of women with Congenital Heart Disease (CHD) regarding sexuality, pregnancy and contraception., Study Design: 536 women with CHD, aged 29 years (18-75 years) underwent clinical assessment and completed a questionnaire regarding sources of information they had received about sexuality, pregnancy and contraception., Results: The sources where affected women sought information regarding sexuality, pregnancy or contraception were wide spread and varied between the different age groups. Not only the treating physician, but also friends were the main information sources. Written information from sources such as newspapers, magazines, books and also the internet were used less often. Only few women received information from affected patients. The women rated their level of information (on a level up to 10) regarding sexuality with a median of 3.5, and with a median of only 5 regarding contraception as well as pregnancy., Conclusions: Current counseling practice for pregnancy and contraception in women with CHD is inadequate. Failure to give knowledgeable family planning advice appropriate for the individual risk profile in this high-risk patient group can have hazardous consequences and cause an unnecessary risk for mother and child. Many doctors fail to confront their patients with congenital heart defects early with issues of regarding sexuality, pregnancy and contraception and to advise them adequately. A cooperative approach involving congenital cardiologists as well as experienced gynecological endocrinologists with appropriate knowledge about CHD is indispensable.

There is a linear relationship between maternal height and birth weight. For each 1 cm increase in maternal height, birth weight increases by 16.7 g. Birth weight percentiles should be calculated by taking maternal height into account. We present birth weight percentile values for girls and boys born after 23-43 completed weeks of gestation for 5 maternal height groups. With these percentiles "genetically" small and "genetically" large, but healthy, neonates can be classified more adequately. The calculations are based on data of about 2.2 million singleton pregnancies from the German Perinatal Survey of 1995-2000., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Afterbirth tissues, which include the umbilical cord, placenta, amnion, and cord blood, are usually discarded. Recent progress in regenerative medicine suggests that we re-evaluate these tissues and assess their therapeutic potential., Methods: Firstly the unique properties of afterbirth tissues and their current use in regenerative medicine are summarised. Then we introduce the cooperation of our institutions and our experiences regarding the collection and utilisation of afterbirth tissues., Results: A literature survey suggests that besides the well-known transplantation of hematopoietic stem cells from cord blood, afterbirth tissues were also used as a source of stem cells, progenitor cells, differentiated cells, and blood vessels for tissue engineering purposes. According to our own experience, the two participating OB/GYN departments and the blood donation service were able to organise a sufficient supply of umbilical cords for research purposes. The yield correlated with incentives for the midwives. A total of more than 4,300 cords was collected for experiments designed to create small caliber vessel grafts. The contamination rate was low. Birth mode significantly affected umbilical vein function, whereas ischaemia for up to 40 h did not have any deleterious effects. Umbilical veins were cryopreserved with a moderate loss of function. Fresh umbilical veins were endothelium-denuded and reseeded with endothelial cells harvested from coronary artery disease patients to generate an autologous surface., Conclusions: Afterbirth tissues have unique properties which make them ideally suited for regenerative medicine. These tissues can be procured and utilised in research facilities even in the absence of an in-house birthing centre., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The composition of long-chain PUFAs (LCPUFAs) in the maternal diet may affect obesity risk in the mother's offspring., Objective: We hypothesized that a reduction in the n-6 (omega-6):n-3 (omega-3) LCPUFA ratio in the diet of pregnant women and breastfeeding mothers may prevent expansive adipose tissue growth in their infants during the first year of life., Design: In a randomized controlled trial, 208 healthy pregnant women were randomly assigned to an intervention (1200 mg n-3 LCPUFAs as a supplement per day and a concomitant reduction in arachidonic acid intake) or a control diet from the 15th wk of pregnancy to 4 mo of lactation. The primary outcome was infant fat mass estimated by skinfold thickness (SFT) measurements at 4 body sites at 3-5 d, 6 wk, and 4 and 12 mo postpartum. Secondary endpoints included sonographic assessment of abdominal subcutaneous and preperitoneal fat, fat distribution, and child growth., Results: Infants did not differ in the sum of their 4 SFTs at ≤1 y of life [intervention: 24.1 ± 4.4 mm (n = 85); control: 24.1 ± 4.1 mm (n = 80); mean difference: -0.0 mm (95% CI: -1.3, 1.3 mm)] or in growth. Likewise, longitudinal ultrasonography showed no significant differences in abdominal fat mass or fat distribution., Conclusions: We showed no evidence that supplementation with n-3 fatty acids and instructions to reduce arachidonic acid intake during pregnancy and lactation relevantly affects fat mass in offspring during the first year of life. Prospective long-term studies are needed to explore the efficacy of this dietary approach for primary prevention. This trial was registered at clinicaltrials.gov as NCT00362089.

Aim: "Late motherhood" is associated with greater perinatal risks but the term lacks precise definition. We present an approach to determine what "late motherhood" associated with "high risk" is, based on parity and preterm birth rate. Materials and Methods: Using data from the German Perinatal Survey of 1998-2000 we analysed preterm birth rates in women with zero, one, or two previous live births. We compared groups of "late" mothers (with high preterm birth rates) with "control" groups of younger women (with relatively low preterm birth rates). Data of 208 342 women were analysed. For women with zero (one; two) previous live births, the "control" group included women aged 22-26 (27-31; 29-33) years. Women in the "late motherhood" group were aged > 33 (> 35; > 38) years. Results: The "late motherhood" groups defined in this way were also at higher risk of adverse perinatal events other than preterm birth. For women with zero (one; two) previous live births, normal cephalic presentation occurred in 89 % (92.7 %; 93.3 %) in the "control" group, but only in 84.5 % (90 %; 90.4 %) in the "late motherhood" group. The mode of delivery was spontaneous or at most requiring manual help in 71.3 % (83.4 %; 85.8 %) in the "control" group, but only in 51.4 % (72.2 %; 76.4 %) in the "late motherhood" group. Five-minute APGAR scores were likewise worse for neonates of "late" mothers and the proportion with a birth weight ≤ 2499 g was greater. Conclusion: "Late motherhood" that is associated with greater perinatal risks can be defined based on parity and preterm birth rate.

Inoculation of soybean (Glycine max) plants with Phakopsora pachyrhizi, the causal organism of Asian soybean rust, elicits a biphasic response characterized by a burst of differential gene expression in the first 12 h. A quiescent period occurs from 24 to 48 h after inoculation, in which P. pachyrhizi continues to develop but does not elicit strong host responses, followed by a second phase of intense gene expression. To correlate soybean responses with P. pachyrhizi growth and development, we inoculated the soybean cultivar Ankur (accession PI462312), which carries the Rpp3 resistance gene, with avirulent and virulent isolates of P. pachyrhizi. The avirulent isolate Hawaii 94-1 elicits hypersensitive cell death that limits fungal growth on Ankur and results in an incompatible response, while the virulent isolate Taiwan 80-2 grows extensively, sporulates profusely, and produces a compatible reaction. Inoculated leaves were collected over a 288-h time course for microarray analysis of soybean gene expression and microscopic analysis of P. pachyrhizi growth and development. The first burst in gene expression correlated with appressorium formation and penetration of epidermal cells, while the second burst of gene expression changes followed the onset of haustoria formation in both compatible and incompatible interactions. The proliferation of haustoria coincided with the inhibition of P. pachyrhizi growth in the incompatible interaction or the beginning of accelerated growth in the compatible interaction. The temporal relationships between P. pachyrhizi growth and host responses provide an important context in which to view interacting gene networks that mediate the outcomes of their interactions.

Objective: Decreased fetal heart rate variability is associated with higher perinatal morbidity and mortality in intrauterine growth restriction (IUGR). This study used a new method [phase-rectified signal averaging (PRSA)] to calculate acceleration- and deceleration-related fluctuations of the fetal heart rate., Method: Cardiotocograms from 74 growth-restricted and 161 normal fetuses were included. Both groups were matched for gestational age. The transformed PRSA signal was quantified by the acceleration-related parameter-averaged acceleration capacity (AAC) and compared to the standard short-term variation (STV). Mann-Whitney test and receiver operator characteristic (ROC) curves were used for statistical analysis., Results: For AAC, the median values of the IUGR group and control group were 1.97 bpm [interquartile range (IQR): 1.66-2.23] and 2.49 bpm (IQR: 2.24-2.72), respectively. For STV, these values were 5.44 ms (IQR: 4.49-7.38) and 7.79 ms (IQR: 6.35-9.66), respectively. The area under the ROC curve was 81.4% for AAC and 70.5% for STV., Conclusion: The results of AAC are in both groups comparable to STV. Longitudinal studies are needed to investigate the association of AAC with the clinical outcome of the newborn., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objective: We report the case of a 46-year-old woman presenting with acute chest pain in the 20th week of a twin pregnancy after oocyte donation., Case Report: The Patient's medical history comprised several cardiovascular risk factors, such as hypertension, obesity, hypercholesterolemia, smoking, and a positive family history. After diagnosis of myocardial infarction, coronary catheterization and stenting was performed. Ten weeks later, Cesarean was indicated because of severe superimposed preeclampsia with lung edema. Mother and babies recovered uneventfully., Conclusion: In respect to increasing rates of higher maternal age and obesity during pregnancy, more attention to maternal health is required, particularly in programs for assisted reproductive techniques.

The present study reports on contraceptive use, methods used, and counseling received on contraceptive issues for women with congenital heart disease and provides a brief review of current knowledge of the risks in relation to the different cardiac situations encountered with these specific patients. A total of 536 consecutive adult women with congenital heart disease (median age 29 years) were recruited from 2 tertiary care centers. They underwent a clinical assessment and completed a questionnaire regarding their contraceptive use. Oral contraceptives, condoms, and intrauterine devices were the most commonly used methods. Pregnancy occurred in almost every tenth woman despite the use of contraception. We identified a substantial number of women (20%) who were presently using contraceptive methods that were contraindicated for their specific cardiac condition. Additionally, a high proportion of patients (28%), in the group with high pregnancy-associated risks, were not using contraception despite having a sexual relationship. In our study, 43% of the women had not been counseled about contraception, and 48% had not been informed of the pregnancy-related risks by their treating physician. In conclusion, timely and competent counseling about contraception is important for women with congenital heart disease. Collaboration between cardiologists and gynecologists should be strengthened. Failure to give adequate family planning advice to this patient group could have hazardous consequences, causing an unnecessary risk to mother and child., (Copyright © 2010 Elsevier Inc. All rights reserved.)