Marc Charland

Combining biochemical and ultrasonographic markers in predicting preeclampsia : a systematic review

BACKGROUND Early identification of pregnant women at risk for preeclampsia is a priority to implement preventive measures. Some biochemical and ultrasonographic parameters have shown promising predictive performance, but so far there is no clinically validated screening procedure. CONTENT Using a series of keywords, we reviewed electronic databases (Medline, Embase, all records to May 2009) reporting the performance of biological and ultrasonographic markers to predict preeclampsia, both single markers and combinations of markers. We analyzed the data according to gestational age and risk levels of the studied populations. We evaluated the methodological quality of included publications using QUADAS (quality assessment of diagnostic accuracy studies). We identified 37 relevant studies that assessed 71 different combinations of biochemical and ultrasonographic markers. Most studies were performed during the second trimester on small-scale high-risk populations with few cases of preeclampsia. Combinations of markers generally led to an increase in sensitivity and/or specificity compared with single markers. In low-risk populations, combinations including placental protein 13 (PP13), pregnancy-associated plasma protein A (PAPP-A), a disintegrin and metalloprotease-12 (ADAM12), activin A, or inhibin A measured in first or early second trimester and uterine artery Doppler in second trimester appear promising (sensitivity 60%-80%, specificity >80%). In high-risk populations, the combination of PP13 and pulsatility index in first trimester showed 90% sensitivity and 90% specificity in a single study limited to severe preeclampsia. SUMMARY Combinations of biochemical and ultrasonographic markers improved the performance of early prediction of preeclampsia. From a perspective of integrative medicine, large population-based studies evaluating algorithms combining multiple markers are needed, if screening approaches are to be eventually implemented.

Decisional needs assessment regarding Down syndrome prenatal testing: a systematic review of the perceptions of women, their partners and health professionals

To identify decisional needs of women, their partners and health professionals regarding prenatal testing for Down syndrome through a systematic review.

Candidate biochemical markers for screening of pre-eclampsia in early pregnancy

Abstract Pre-eclampsia (PE) and other hypertensive disorders of pregnancy (HDP) are a leading cause of adverse outcomes. Their pathophysiology remains elusive, hampering the development of efficient prevention. The onset of HDP and PE and the severity of their clinical manifestations are heterogeneous. The advent of preventive measures, such as low-dose aspirin that targets high-risk women, emphasizes the need of better prediction. Until recently, only environmental information and maternal risk factors were considered, with equivocal predictive value. No validated screening procedures were available to identify at-risk women despite the emergence of Doppler ultrasonography parameters for the uterine artery (e.g., pulsatility index and bilateral notching) and pathophysiological biochemical markers (e.g., angiogenesis, inflammation, and endothelial dysfunction). Owing to its heterogeneity and lack of specific, sensitive markers among those studied so far (>200), PE is unlikely to be detected early by a single predictive parameter. Systematic reviews have concluded that no single test fulfilling World Health Organization criteria for biomarker selection can diagnose/predict a disease. However, by combining antenatal risk factors, clinical parameters, as well as biophysical and biochemical markers into multivariate algorithms, the risk of PE can be estimated with performance levels that could reach clinical utility. Performance characteristics of selected algorithms will be presented and discussed with respect to transferability to different geographic and healthcare environments.

Linking preeclampsia and cardiovascular disease later in life.

Abstract Preeclampsia (PE), which is defined as new onset hypertension after 20 weeks of pregnancy accompanied by proteinuria, is characterized by inadequate placentation, oxidative stress, inflammation and widespread endothelial dysfunction. A link between PE and long-term risk of cardiovascular disease (CVD) was suggested by retrospective studies, which found that PE was associated with a 2–3-fold risk of CVD later in life, with a 5–7-fold risk in the case of severe and/or early-onset PE. Recently, meta-analyses and prospective studies have confirmed the association between PE and the emergence of an unfavorable CVD risk profile, in particular a 3–5-fold increased prevalence of the metabolic syndrome only 8 years after the index pregnancy. PE and CVD share many risk factors, including obesity, hypertension, dyslipidemia, hypercoagulability, insulin resistance and both entities are characterized by endothelial dysfunction. PE and CVD are complex traits sharing common risk factors and pathophysiological processes, but the genetic link between both remains to be elucidated. However, recent evidence suggests that genetic determinants associated with the metabolic syndrome, inflammation and subsequent endothelial dysfunction are involved. As the evidence now supports that PE represents a risk factor for the emergence of the metabolic syndrome and CVD later in life, the importance of long-term follow-up assessment of CVD risk beginning early in women with a history of PE must be considered and translated into new preventive measures.

Development and description of GETT: a Genetic testing Evidence Tracking Tool

Abstract Background: The completion of the Human Genome Project has increased the pace of discovery of genetic markers for disease. Despite tremendous efforts in fundamental research, clinical applications still lag behind expectations, partly due to the lack of effective tools to systematically search for and summarize published data relative to the clinical assessment of new diagnostic molecular tests. Methods: Through a collaborative process using published tools and an expert panel, we developed a detailed checklist of the evidence that needs to be collected or produced to evaluate the potential usefulness of a new molecular diagnostic test. This tool is called GETT, for Genetic testing Evidence Tracking Tool. Results: GETT allows 1) researchers to summarize the current evidence and to identify knowledge gaps for further research and; 2) stakeholders to collect data related to a given molecular test and improve their decision-making process. GETT comprises 72 clearly defined items/questions, grouped into 10 categories and 26 sub-themes, including an overview of disease epidemiology and genetics, the available diagnostic tools, and their analytical and clinical performances, availability of quality control programs, laboratory and clinical best practice guidelines, clinical utility, and impact on health care and psycho-social, ethical and legal implications. It also includes a summary of the evidence available and attempts to prioritise knowledge gaps related to the testing. We also compare GETT to other existing frameworks. Conclusions: This systematic evidence-based tracking tool, which is more detailed than existing frameworks and provides clear definition for each item, will help streamline collection of the available evidence to appraise the potential for clinical application of new molecular diagnostic tests and prioritize research to produce the evidence-base relative to the clinical implementation of molecular diagnostic tests. Clin Chem Lab Med 2010;48:1397–407.

Pregnancy Disorders and Perinatal Outcomes

Embryo implantation is a complex process; primary step in implantation is the initiation of dialogue between free floating blastocyst and the receptive endometrium. This is followed by a stable adhesion of the blastocyst anchors to the endometrial basal lamina and stromal extracellular matrix. The last step is invasion of the embryo through the luminal epithelium and its basal lamina into the uterine stroma. Successful embryo implantation depends up on number of factors like steroid hormones (progesterone, estrogen), Cyclooxygenases, prostaglandins, cytokines, growth factors, transcription factors (HOXA-10 and HOXA-11), and adhesion molecules (integrins, selectins, cadherins, mucins) and receptive endometrium. Importantly, there is timely regulation of these factors and their cross talk which mediates the implantation process. Blastocyst is unable to implant successfully if there is deregulation in any of these factors leading to pregnancy loss. In this chapter we reviewed the information available till date to provide possible causes of implantation failure and its positive outcomes.