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

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.