Improving prediction and diagnosis of pre-eclampsia; better outcomes for mother and infant? (#121)
Pre-eclampsia remains a major cause of maternal and neonatal mortality and morbidity worldwide. Despite some improvement in understanding of the aetiology, there is no cure other than delivery. Since pre-eclampsia may occur from the late second trimester onwards, and may be associated with fetal growth restriction, the disorder is associated with a high incidence of premature birth and small for gestational age deliveries, with risk of immediate and longer term problems for the health of the child. There are, nonetheless, benefits of accurate prediction of pre-eclampsia, including prophylactic treatment with low dose aspirin which confers some protection against development of the disorder, and stratification of high risk women to heightened antenatal surveillance.
Despite enormous effort there is at present inadequate evidence for at test that can recommended for routine screening for risk of pre-eclampsia in pregnancy . Risk assessment based on clinical history alone is currently advised but is at best a modest predictor of outcome, although recent studies in both high and low risk women suggest that current estimates of risk could be improved upon (Chappell et al, 2008; Bramham et al, 2011; North et al 2011). An accurate test for prediction is likely to develop from a combination of clinical risk factors and biomarkers and a first trimester screening test based on clinical risk, uterine artery Doppler and biomarkers of placental origin has been reported, but leads to a high false positive rate which may lead to unnecessary anxiety for the mother for the rest of her pregnancy. Hitherto the biomarker approaches have focussed on the more obvious candidate biomarkers, predominantly of placental origin, but ‘omics techno1 1 logies (metabolomics, proteomics) have identified new molecules with predictive potential, including some characterised in our laboratory from studies of the urinary proteome.
Accurate diagnosis of pre-eclampsia which is at present based on measurement of the blood pressure and proteinuria can also be troublesome, particularly in women with underlying disorders such as renal disease where incorrect diagnosis may lead to inappropriate treatment. Here, new tests based on the measurement of placental placental growth factor [PlGF] and the vascular endothelial factor [VEGF], binding protein, sFlt-1, are showing promise and are currently being evaluated.
New methods for prediction and diagnosis of pre-eclampsia in development could improve antenatal care, and thereby the potential for better health in mother and infant.
- Bramham K, Briley AL, Seed P, Poston L, Shennan AH, Chappell LC. Adverse maternal and perinatal outcomes in women with previous preeclampsia: a prospective study. Am J Obstet Gynecol: 2011; 201; 512.e1-9.
- Chappell LC, Enye S, Seed P, Briley AL, Poston L, Shennan AH. Adverse perinatal outcomes and risk factors for preeclampsia in women with chronic hypertension: a prospective study. Hypertension. 2008:1002-9
- North RA, McCowan LM, Dekker GA, Poston L, Chan EH, Stewart AW, Black MA, Taylor RS, Walker JJ, Baker PN, Kenny LC. Clinical risk prediction for pre-eclampsia in nulliparous women: development of model in international prospective cohort. BMJ. 2011; 342:d1875