R. Axt-Fliedner

Qualitative venous Doppler flow waveform analysis in preterm intrauterine growth-restricted fetuses with ARED flow in the umbilical artery--correlation with short-term outcome.

The aim of this retrospective study was to examine the significance of severe Doppler waveform abnormalities in the ductus venosus (DV) and the umbilical vein (UV) for the prediction of adverse outcomes in very preterm growth‐restricted fetuses with absent or reversed end‐diastolic flow in the umbilical artery (UA) at 24–34 weeks of gestation.

Right aortic arch detected in fetal life

To evaluate the prenatal distribution, associated conditions and outcome of the different types of right aortic arch (RAA) detected in fetal life.

Isolated ventricular septal defects detected by color Doppler imaging: evolution during fetal and first year of postnatal life

To evaluate the development during gestation and up to 1 year postnatally of isolated small ventricular septal defects (VSDs) not visible by gray‐scale imaging and detected only on color Doppler fetal echocardiography.

miRNA expression profiling in formalin-fixed and paraffin-embedded placental tissue samples from pregnancies with severe preeclampsia

Abstract Aims: Micro RNAs (miRNAs) are small, single-strand RNAs, playing an important role in post-transcriptional gene regulation. The placenta is considered to play a key role in pathogenesis of preeclampsia. The purpose of this study was to demonstrate deregulation of miRNAs in placentas with preeclampsia using formalin-fixed and paraffin-embedded (FFPE) tissues. Methods: Expression levels of 162 miRNAs were measured in FFPE placental tissues (5 with severe preeclampsia, 5 from a control group) using a quantitative qPCR based technique. Results: Six miRNAs were more than 2-fold over-expressed in severe preeclampsia: let-7b, miRNA-302*, miRNA-104, miRNA-128a, miRNA-182* and miRNA-133b. Gene ontology analyses were performed using the algorithms “TargetScanS”, “microRNA”, and “PicTar”. Conclusions: Two of the up-regulated miRNAs (miRNA-182* and miRNA-133b) are putative regulators of the transcript variants 1 and 2 of the BCL2-like gene, which controls apoptosis. miRNA-182* is also a probable angiogenesis regulator via angiogenin and VEGF-B. Apoptosis and angiogenesis are major mechanisms presumed to be involved in the pathogenesis of preeclampsia. Moreover, usability of qPCR technique based miRNA profiling for FFPE tissues was proofed. Hence FFPE tissue is the most widely used material for retrospective clinical studies, this method has a great property for future investigations in placenta research.

Analysis of Vitamin D-receptor (VDR) and Retinoid X-receptor α in Breast Cancer

The expression of vitamin D-receptor (VDR) and retinoid X-receptor α (RXR-α) has been analysed immunohistochemically in benign (n = 62 and n = 5 respectively) and malignant (n = 228 and n = 15 respectively) breast tissue samples using a monoclonal antibody 9A7γ against VDR and a polyclonal antibody against RXR-α. A recently developed immunoreactive scoring method (IRS) was employed. The expression of VDR was detected at the RNA-level using the reverse transcriptase–polymerase chain reaction. A statistically significant higher expression of VDR at the protein level was seen in breast cancer compared with benign breast tissue, whereas at the mRNA level no visible differences in the expression of VDR were found. A higher expression of RXR-α was seen in breast cancer compared with benign breast tissue. Our findings indicate that breast tissue may be a new target organ for therapeutically applied vitamin D and retinoid analogues. VDR and RXR-α are upregulated at the protein level in breast carcinomas as compared to normal breast tissue, indicating a possibly increased sensitivity to therapeutically applied vitamin D analogues. New vitamin D analogues exerting less calcemic side effects may be promising new drugs for the treatment or chemoprevention of breast carcinomas as well as of precancerous breast lesions. Combination therapies of vitamin D and retinoid analogues with fewer side effects seen promising for the treatment of breast cancer.

Spectrum and outcome of prenatally diagnosed fetal tumors

To describe the spectrum of prenatally diagnosed fetal tumors, and the course and fetal outcome in affected pregnancies.

Percutaneous minimal-access fetoscopic surgery for spina bifida aperta. Part II: maternal management and outcome

To assess maternal morbidity and outcome in women undergoing minimal‐access fetoscopic surgery for spina bifida aperta.

Prevalence, Characteristics and Perinatal Outcome of Fetal Ventriculomegaly in 29,000 Pregnancies Followed at a Single Institution

Objective: Our purpose was to assess the impact of prenatally diagnosed ventriculomegaly (VM) on the course of advancing pregnancy and the postnatal outcome of affected fetuses. Methods: In this retrospective survey 109/28,935 (3.8 per 1,000) singleton pregnancies with abnormal width of the fetal lateral ventricle system diagnosed by antenatal ultrasound examination at the University Hospital of Schleswig-Holstein, Campus Lübeck, were reviewed between 1993 and 2007. Clinical data and pregnancy outcome information were derived from a standardized parental questionnaire or from hospital records. Postnatal follow-up was obtained in >90%. Results: Forty-seven cases with isolated VM (IVM; 43%) and 62 fetuses (57%) with nonisolated VM were diagnosed. In the IVM group 19 cases had mild and 28 fetuses severe VM. Of 62 cases with non-IVM there were 32 with mildly dilated ventricles and 30 had severe enlargements. Chromosomal aberrations were present in 5 fetuses (4.6%) of the non-IVM group. Thirty-four pregnancies (31%) were terminated on parental request (10 IVM/24 non-IVM). The risk of abnormal neurodevelopmental outcome was highest in the presence of associated anomalies (irrespective of the extent of dilatation) and in cases with severe IVM (91 and 68%, respectively). In contrast, 13/14 children with mild IVM showed an age-related normal psychomotor behavior. Fetuses with severe VM had a 2.2- (IVM) to 3.6-fold (non-IVM) elevated risk of progressive dilatations compared to mild VM. In our study the fetuses with asymmetrical bilateral IVM tended to have severe ventricular enlargements more often. Conclusions: As reported previously we found a positive association between neurodevelopmental delay and the degree of lateral ventricular dilatation. The presence of additional abnormalities is generally a poor prognostic sign and accompanied by a nonfavorable postnatal outcome.

Fetal micrognathia: objective assessment and associated anomalies on prenatal sonogram

To determine the accuracy and characteristics of prenatally detected fetal micrognathia.

Fetal Loss Rate and Associated Risk Factors After Amniocentesis, Chorionic Villus Sampling and Fetal Blood Sampling

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.