Two- versus three-dimensional ultrasound in the second and third trimester of pregnancy: impact on recognition and maternal-fetal bonding. A prospective pilot study

Objective: To assess the impact of three-dimensional (3D) versus two-dimensional (2D) ultrasound (US) on maternal-fetal bonding. Study design: Prospective randomized pilot study among low risk women with singleton fetuses in the second and third trimester. Dependent on the randomization pattern, US was commenced either with 2D US or 3D US and the effects were recorded with standardized questionnaires. Results: Sixty patients were included. Although the quality of 2D US, assessed by the examinator, was superior to 3D US, maternal recognition was higher with 3-D US (P=0.004). With 2D US, nulliparous patients had significantly more difficulties visualizing the fetus, than multiparous (P=0.03). However, the maternal preference of 3D US had no significant impact on maternal-fetal bonding. Conclusion: Ultrasound had no significant effect on maternal-fetal bonding. Three-dimensional images may facilitate recognition of the fetus, but 3D US did not have higher impact on maternal-fetal bonding. This finding may be a reason not to consider 3D ultrasound for routine scannin

Determination of fetal chromosome aberrations from fetal DNA in maternal blood: has the challenge finally been met?

The analysis of cell-free fetal nucleic acids in maternal blood for prenatal diagnosis has been transformed by several recent profound technology developments. The most noteworthy of these are ‘digital PCR' and ‘next-generation sequencing' (NGS), which might finally deliver the long-sought goal of noninvasive detection of fetal aneuploidy. Recent data, however, indicate that NGS might even be able to offer a much more detailed appraisal of the fetal genome, including paternal and maternal inheritance of point mutations for mendelian disorders such as β-thalassaemia. Although these developments are very exciting, in their current form they are still too complex and costly, and will need to be simplified considerably for their optimal translation to the clinic. In this regard, targeted NGS does appear to be a step in the right direction, although this should be seen in the context of ongoing progress with the isolation of fetal cells and with proteomic screening marker

Cell-free foetal DNA in maternal plasma does not appear to be derived from the rich pool of cell-free foetal DNA in amniotic fluid

Background: Large quantities of cell-free foetal DNA have been detected in amniotic fluid, and it has been proposed that this material may contribute to the pool of cell-free foetal DNA in maternal plasma. Methods: Twelve maternal blood samples were obtained from pregnant women about to undergo an amniocentesis. Cell-free DNA was extracted from the maternal plasma samples and the matched amniotic fluid samples. The amount of cell-free foetal DNA was quantified by real-time PCR assays for the SRY and RHD genes. Results: Amniotic fluid was found to contain vast quantities of cell-free DNA (median concentration = 3,978 copies/ml amniotic fluid). The concentration of cell-free foetal DNA in maternal plasma was much lower (median concentration = 96.6 copies/ml maternal plasma). No significant correlation could, however, be determined between these two pools of cell-free foetal DNA. Conclusions: Our data confirm that amniotic fluid contains prodigious quantities of cell-free foetal DNA, but as no relationship exists between this material and that in the maternal circulation, it is unlikely that the amnion contributes to the presence of cell-free foetal DNA in maternal plasm

Quantitative Proteomics Analysis of Maternal Plasma in Down Syndrome Pregnancies Using Isobaric Tagging Reagent (iTRAQ)

Currently no specific biomarkers exist for the screening of pregnancies at risk for down syndrome (DS). Since a quantitative proteomic approach with isobaric labelling (iTRAQ) has recently been suggested to be highly suitable for the discovery of novel plasma biomarkers, we have now used this method to examine for potential quantitative changes in the plasma proteome of the pregnancies bearing DS fetuses in comparison to normal healthy babies. In our study, we used plasma from six women with DS pregnancies and six with uncomplicated pregnancies care were taken to match cases and controls for gestational and maternal age, as these could be a confounder. In our quantitative proteomics analysis we were able to detect 178 proteins using iTRAQ labelling in conjunction with 4800 MALDI TOF/TOF. Amongst these we observed changes in βHCG, a known screening marker for DS, indicating that our assay was functional. We found a number of elevated proteins Ig lambda chain C region, serum amyloid P-component, amyloid beta A4, and under expressed proteins like gamma-actin and titin in DS pregnancies. These proteins are also found in the sera of patients with Alzheimer disease, which share similar pathologies of DS. Our study therefore indicates that the iTRAQ labelling approach may be indeed useful for the detection of novel biomarkers

The special role of ultrasound for screening, staging and surveillance of malignant ovarian tumors: distinction from other methods of diagnostic imaging

Ovarian cancer is the most aggressive gynecologic malignancy, with a 5-year survival rate ranging around 40%. A crucial factor influencing the prognosis is early detection of a suspicious mass and referral to a gynecologic oncology center for further diagnosis, staging and debulking surgery. Here, we present the different imaging methods ultrasound (US), magnetic resonance imaging, computer tomography (CT) and 18F-fluoro-deoxyglucose positron emission tomography (PET)/CT that are used for the characterization, diagnosis, staging and surveillance of ovarian cancer. In this review, we focus on US and discuss in detail the advantages and the limitations, as well as the appropriate indications for each of the individual imaging techniques

The special role of ultrasound for screening, staging and surveillance of malignant ovarian tumors: distinction from other methods of diagnostic imaging

Ovarian cancer is the most aggressive gynecologic malignancy, with a 5-year survival rate ranging around 40%. A crucial factor influencing the prognosis is early detection of a suspicious mass and referral to a gynecologic oncology center for further diagnosis, staging and debulking surgery. Here, we present the different imaging methods ultrasound (US), magnetic resonance imaging, computer tomography (CT) and 18F-fluoro-deoxyglucose positron emission tomography (PET)/CT that are used for the characterization, diagnosis, staging and surveillance of ovarian cancer. In this review, we focus on US and discuss in detail the advantages and the limitations, as well as the appropriate indications for each of the individual imaging techniques

Wissen können, dürfen, wollen?: genetische Untersuchungen während der Schwangerschaft

Neue Methoden der Genomanalyse erlauben es, im Blut einer schwangeren Frau festzustellen, ob krankhafte genetische Abweichungen beim Embryo vorliegen. Damit wird es vergleichsweise einfach, schon in einer frühen Phase der Schwangerschaft Aussagen über Chromosomen-Anomalien und weitere genetische Merkmale des Ungeborenen zu erhalten. Die seit wenigen Jahren erhältlichen nicht-invasiven Pränataltests (NIPT) sind gemäss ersten Erfahrungen sehr verlässlich, zudem entfallen die Risiken für den Fötus, die mit einer invasiven Untersuchung wie z.B. der Fruchtwasserpunktion einhergehen. Mit einer breiteren Anwendung der NIPT und mit der zunehmenden Anzahl von Krankheitsrisiken, die damit untersucht werden können, sind offene Fragen verbunden. Welche Tests sind sinnvoll? Wie gehen die Betroffenen mit den Informationen um? Wie wird die Beratung sichergestellt? In der interdisziplinären Studie werden Chancen und Risiken von vorgeburtlichen genetischen Untersuchungen abgeschätzt. Die Studie zeigt auf, wie sich die neuen Tests auf die Zukunft der pränatalen Diagnostik auswirken könnten, analysiert gesellschaftliche, ethische, rechtliche und ökonomische Fragen und formuliert Empfehlungen

DEGUM, ÖGUM, SGUM and FMF Germany Recommendations for the Implementation of First-Trimester Screening, Detailed Ultrasound, Cell-Free DNA Screening and Diagnostic Procedures

First-trimester screening between 11 + 0 and 13 + 6 weeks with qualified prenatal counseling, detailed ultrasound, biochemical markers and maternal factors has become the basis for decisions about further examinations. It detects numerous structural and genetic anomalies. The inclusion of uterine artery Doppler and PlGF screens for preeclampsia and fetal growth restriction. Low-dose aspirin significantly reduces the prevalence of severe preterm eclampsia. Cut-off values define groups of high, intermediate and low probability. Prenatal counseling uses detection and false-positive rates to work out the individual need profile and the corresponding decision: no further diagnosis/screening - cell-free DNA screening - diagnostic procedure and genetic analysis. In pre-test counseling it must be recognized that the prevalence of trisomy 21, 18 or 13 is low in younger women, as in submicroscopic anomalies in every maternal age. Even with high specificities, the positive predictive values of screening tests for rare anomalies are low. In the general population trisomies and sex chromosome aneuploidies account for approximately 70 % of anomalies recognizable by conventional genetic analysis. Screen positive results of cfDNA tests have to be proven by diagnostic procedure and genetic diagnosis. In cases of inconclusive results a higher rate of genetic anomalies is detected. Procedure-related fetal loss rates after chorionic biopsy and amniocentesis performed by experts are lower than 1 to 2 in 1000. Counseling should include the possible detection of submicroscopic anomalies by comparative genomic hybridization (array-CGH). At present, existing studies about screening for microdeletions and duplications do not provide reliable data to calculate sensitivities, false-positive rates and positive predictive values

[Ultrasound findings in fetal infection]

Infections acquired in utero or during the birth process are a significant cause of fetal and neonatal mortality and an important contributor to early and later childhood morbidity. Advances in ultrasound, invasive prenatal procedures and molecular diagnostics have allowed in utero evaluation and given rise to more timely and accurate diagnosis in infected fetuses. Transplacental transmission of the infectious agent, even in subclinical maternal infection, may result in a severe congenital syndrome. Prenatal detection of infection is based on fetal sonographic findings and polymerase chain reaction to identify the specific agent. Nevertheless, most affected fetuses appear sonographically normal, but serial scanning may reveal evolving findings. Sonographic fetal abnormalities may be indicative of fetal infections, although they are generally not sensitive or specific. These include growth restriction, hydrops, ventriculomegaly, hydrocephaly, microcephaly, intracranial or hepatic calcifications, ascites, hepatosplenomegaly, echogenic bowel, placentomegaly, and abnormal amniotic fluid volume. When abnormalities are detected on ultrasound, a thorough fetal evaluation is recommended because of potential multiorgan involvement. The sonologist should understand the limitations of ultrasound. Patients should be counseled that ultrasound is not a sensitive test for fetal infection and that a normal fetal anatomy survey cannot reliably predict a favorable outcome