Frequency of Miscarriage/Stillbirth and Terminations of Pregnancy Among Women With Congenital Heart Disease in Germany, Hungary and Japan.

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).

What is the "normal" fetal heart rate?

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.

Ex vivo detection of apoptotic trophoblast cells applying flow cytofluorometry and immunocytochemistry using M30 antibody directed to the cytokeratin 18 neo-epitope.

Apoptosis of placental trophoblast cells has become the subject of intensive research. Recently, a monoclonal antibody (M30) directed against a neo-epitope of cytokeratin 18, that is formed after cleavage of this cytoskeletal protein by caspases, was shown to be of advantage over other tests for the detection of trophoblast cell apoptosis. In the present study, we describe a method for the enrichment of highly pure villous trophoblast cells based on the proteolytic digestion of placental tissue, density gradient separation of dissected cells, and immunoelimination of contaminating, non-trophoblast cells employing an antibody to the HLA class I antigen. The high purity (94-99%) of the trophoblast cell preparation was shown by antibody staining for cytokeratin 7 and absence of vimentin. Furthermore, we demonstrate that after a simple permeabilization and fixation step with 90% methanol and using the M30 CytoDeath, FITC-conjugated antibody, apoptotic trophoblast cells could be distinguished from non-apoptotic cells by flow cytofluorometry in a highly quantitative and sensitive fashion. Our protocol is an improvement over previously used methods such as immunocytochemistry as it allows to differentiate rapidly between competent and apoptotic trophoblast cells by the quantitative method of flow cytofluorometry.