Multiplex ligation-dependent probe amplification versus karyotyping in prenatal diagnosis: the M.A.K.E. study

Abstract BACKGROUND: In the past 30 years karyotyping was the gold standard for prenatal diagnosis of chromosomal aberrations in the fetus. Traditional karyotyping (TKT) has a high accuracy and reliability. However, it is labor intensive, the results take 14-21 days, the costs are high and unwanted findings such as abnormalities with unknown clinical relevance are not uncommon. These disadvantages challenged the practice of karyotyping. Multiplex ligation-dependent probe amplification (MLPA) is a new molecular genetic technique in prenatal diagnosis. Previous preclinical evidence suggests equivalence of MLPA and traditional karyotyping (TKT) regarding test performance. METHODS/DESIGN: The proposed study is a multicentre diagnostic substitute study among pregnant women, who choose to have amniocentesis for the indication advanced maternal age and/or increased risk following prenatal screening test. In all subjects, both MLPA and karyotyping will be performed on the amniotic fluid sample. The primary outcome is diagnostic accuracy. Secondary outcomes will be maternal quality of life, women's preferences and costs. Analysis will be intention to treat and per protocol analysis. Quality of life analysis will be carried out within the study population. The study aims to include 4500 women. DISCUSSION: The study results are expected to help decide whether MLPA can replace traditional karyotyping for 'low-risk' pregnancies in terms of diagnostic accuracy, quality of life and women's preferences. This will be the first clinical study to report on all relevant aspects of the potential replacement

Individual accumulation of heterogeneous risks explains perinatal inequalities within deprived neighbourhoods

Dutch' figures on perinatal mortality and morbidity are poor compared to EU-standards. Considerable within-country differences have been reported too, with decreased perinatal health in deprived urban areas. We investigated associations between perinatal risk factors and adverse perinatal outcomes in 7,359 pregnant women participating in population-based prospective cohort study, to establish the independent role, if any, for living within a deprived urban neighbourhood. Main outcome measures included perinatal death, intrauterine growth restriction (IUGR), prematurity, congenital malformations, Apgar at 5 min < 7, and pre-eclampsia. Information regarding individual risk factors was obtained from questionnaires, physical examinations, ultrasounds, biological samples, and medical records. The dichotomous Dutch deprivation indicator was additionally used to test for unexplained deprived urban area effects. Pregnancies from a deprived neighbourhood had an increased risk for perinatal death (RR 1.8, 95% CI [1.1; 3.1]). IUGR, prematurity, Apgar at 5 min < 7, and pre-eclampsia also showed higher prevalences (P < 0.05). Residing within a deprived neighbourhood was associated with increased prevalence of all measured risk factors. Regression analysis showed that the observed neighbourhood related differences in perinatal outcomes could be attributed to the increased risk factor prevalence only, without a separated role for living within a deprived neighbourhood. Women from a deprived neighbourhood had significantly more 'possibly avoidable' risk factors. To conclude, women from a socioeconomically deprived neighbourhood are at an increased risk for adverse pregnancy outcomes. Differences regarding possibly avoidable risk factors imply that preventive strategies may prove effective

Towards a Rigorous Network of Protein-Protein Interactions of the Model Sulfate Reducer Desulfovibrio vulgaris Hildenborough

Protein–protein interactions offer an insight into cellular processes beyond what may be obtained by the quantitative functional genomics tools of proteomics and transcriptomics. The aforementioned tools have been extensively applied to study Escherichia coli and other aerobes and more recently to study the stress response behavior of Desulfovibrio vulgaris Hildenborough, a model obligate anaerobe and sulfate reducer and the subject of this study. Here we carried out affinity purification followed by mass spectrometry to reconstruct an interaction network among 12 chromosomally encoded bait and 90 prey proteins based on 134 bait-prey interactions identified to be of high confidence. Protein-protein interaction data are often plagued by the lack of adequate controls and replication analyses necessary to assess confidence in the results, including identification of potential false positives. We addressed these issues through the use of biological replication, exponentially modified protein abundance indices, results from an experimental negative control, and a statistical test to assign confidence to each putative interacting pair applicable to small interaction data studies. We discuss the biological significance of metabolic features of D. vulgaris revealed by these protein-protein interaction data and the observed protein modifications. These include the distinct role of the putative carbon monoxide-induced hydrogenase, unique electron transfer routes associated with different oxidoreductases, and the possible role of methylation in regulating sulfate reduction

Motivating for a gendered analysis of trends within South African

In South Africa, in the prestigious profession of medicine, women are still in the minority. Men continue to form nearly three quarters of the number of registered practitioners, although social and institutional exclusionary structures have been abolished. It is important to investigate the reasons underlying this state of affairs, which exists despite equality in access to educational opportunities, training and advancement in the profession, and the drastically increased number of female medical student enrolments and graduations during the last decade. What is importantly emerging as a new area for research, especially in the South African case where such studies are lacking, is an investigation into the factors specifically influencing women doctors' participation and experiences during education and in the profession, in an effort to more comprehensively explain current gender trends. South African Journal of Higher Education Vol. 22 (4) 2008: pp. 920-93

Prenatal diagnosis in the Netherlands, 1991-2000: Number of invasive procedures, indications, abnormal results and terminations of pregnancy

Objective To provide an overview of invasive prenatal diagnosis in the Netherlands and to analyse trends. Methods Annual results from all centres for invasive prenatal diagnosis in the Netherlands over the period 1991-2000 were combined and described, with particular emphasis on indications, abnormal results, type of invasive procedures, and terminations of pregnancy. Results The percentage of invasive prenatal diagnosis increased from 5% of births in 1991 to 6% in 1996 and subsequently remained at that level. During the study period, the number of pregnant women aged 36 and older increased by 70%, but the number of procedures performed because of maternal age remained stable. The detection rate for abnormal results was 2-3% for maternal age and rose from 9 to 13% for other indications. Other trends during the study period included a relative decrease in cordocentesis (-82%) and chorionic villi biopsy (-18%) in favour of amniocentesis (+48%), and a strong decrease in the number of amniocentesis procedures for increased risk of neural tube defect. In 71% of the cases with abnormal results, the pregnancy was terminated. Conclusion There was a significant decrease in the percentage of pregnant women aged 36 or older who underwent invasive prenatal diagnosis without previous screening. Copyright (C) 2007 John Wiley & Sons, Lt