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.
Subject(s)
Pre-Eclampsia/diagnosis , Biomarkers/metabolism , Embryo Implantation , Female , Humans , Pre-Eclampsia/metabolism , Pre-Eclampsia/pathology , Pre-Eclampsia/physiopathology , Pregnancy , Risk FactorsABSTRACT
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 23-fold risk of CVD later in life, with a 57-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 35-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.
Subject(s)
Cardiovascular Diseases/etiology , Pre-Eclampsia , Cardiovascular Diseases/genetics , Cardiovascular Diseases/physiopathology , Female , Genetic Linkage , Humans , Pre-Eclampsia/genetics , Pre-Eclampsia/physiopathology , Pregnancy , Risk FactorsABSTRACT
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 Ameasured 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. 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.
Subject(s)
Pre-Eclampsia/blood , Pre-Eclampsia/diagnostic imaging , Biomarkers/blood , Female , Humans , Predictive Value of Tests , Pregnancy , UltrasonographyABSTRACT
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.
Subject(s)
Biomarkers/analysis , Pre-Eclampsia/diagnostic imaging , Pre-Eclampsia/diagnosis , Biochemistry/methods , Female , Humans , Pregnancy , Ultrasonography, Prenatal/methodsABSTRACT
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.
Subject(s)
Genetic Testing/methods , Molecular Diagnostic Techniques/methods , Clinical Laboratory Techniques , Decision Support Techniques , HumansABSTRACT
OBJECTIVE: Maternal intake is crucial to pregnancy outcomes. Evidence shows that both nutrient deficiency and excess can have adverse effects. In pregnancy, changes in iron metabolism occur; therefore, dietary reference intakes increase to support expansion of red cells and maternal-fetal transfer of iron. Appropriate and valid assessment tools are required to investigate nutritional concerns in mothers with and without gestational diabetes mellitus (GDM). The objective of this study was to assess the Willett food frequency questionnaire (FFQ) to assess iron intake in women with (n = 15) and without (n = 45) GDM. METHODS: To validate the modified FFQ, estimated total iron intake during the third trimester was compared with biomarkers of iron status such as serum ferritin, soluble transferrin receptor (sTfR), and the sTfR:F index at delivery. Data were tested for normality using the D'Agostino-Pearson test. Differences between groups were tested using t tests or Mann-Whitney tests. Correlations were tested using Spearman's ρ. Significance was set at P < 0.05. RESULTS: Significant crude and energy-adjusted serum ferritin and total iron intake were related (ρ = 0.30; P < 0.05) in women without GDM. Serum ferritin, sTfR, and the sTfR:F index were different (P < 0.05) between women with intakes above and below the recommended levels. Cross-classification showed agreement between methods in mothers with and without GDM; on average, 63% of the women were classified into the same or adjacent quartile when ranked by FFQ and iron status. CONCLUSION: These findings suggest the Willett FFQ is a good tool for assessing total iron intake of French-Canadian pregnant women.
Subject(s)
Anemia, Iron-Deficiency/complications , Diabetes, Gestational/blood , Diet Surveys/standards , Iron/administration & dosage , Nutrition Assessment , Pregnancy/blood , Surveys and Questionnaires/standards , Adult , Anemia, Iron-Deficiency/blood , Biomarkers/blood , Canada , Case-Control Studies , Female , Ferritins/blood , Humans , Iron/blood , Nutritional Status , Pregnancy Trimester, Third , Receptors, Transferrin/blood , Reference Values , Statistics, Nonparametric , Young AdultABSTRACT
OBJECTIVE: To identify decisional needs of women, their partners and health professionals regarding prenatal testing for Down syndrome through a systematic review. METHODS: Articles reporting original data from real clinical situations on sources of difficulty and/or ease in making decisions regarding prenatal testing for Down syndrome were selected. Data were extracted using a taxonomy adapted from the Ottawa Decision-Support Framework and the quality of the studies was assessed using Qualsyst validated tools. RESULTS: In all 40 publications covering 32 unique studies were included. The majority concerned women. The most often reported sources of difficulty for decision-making in women were pressure from others, emotions and lack of information; in partners, emotion; in health professionals, lack of information, length of consultation, and personal values. The most important sources of ease were, in women, personal values, understanding and confidence in the medical system; in partners, personal values, information from external sources, and income; in health professionals, peer support and scientific meetings. CONCLUSION: Interventions regarding a decision about prenatal testing for Down syndrome should address many decisional needs, which may indeed vary among the parties involved, whether women, their partners or health professionals. Very little is known about the decisional needs of partners and health professionals.