Review Article New directions in the prediction of pre-eclampsia Stefan C. KANE, 1 Fabricio Da SILVA COSTA 1,2,3 and Shaun P. BRENNECKE 1,2 1 Department of Perinatal Medicine, The Royal Women’s Hospital, 2 Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, and 3 Monash Ultrasound for Women, Melbourne, Victoria, Australia Pre-eclampsia remains an important worldwide cause of maternal and perinatal morbidity and mortality. Improved prediction of those destined to develop this condition would allow for timely initiation of prophylactic therapy, appropriate antenatal surveillance and better targeted research into preventive interventions. This paper reviews recent research into strategies for the prediction of pre-eclampsia, including the use of maternal risk factors, mean maternal arterial pressure, ultrasound parameters and biomarkers. The most promising strategies involve multiparametric approaches, which use a variety of individual parameters in combination, as has been established in first-trimester aneuploidy screening. The paper concludes with a discussion of the issues around the introduction of such testing into clinical practice. Key words: aspirin, blood pressure, mass screening, pre-eclampsia, pregnancy-induced hypertension. Introduction Pre-eclampsia – de novo proteinuric hypertension that develops after 20 weeks of gestation – is an important obstetric concern in Australia, with recent data from New South Wales identifying a mean incidence of 3.3% in singleton pregnancies, 1 in keeping with global estimates. 2 It remains a major cause of maternal and perinatal morbidity and mortality, both in Australia 3,4 and worldwide. 5 Furthermore, the onset of pre-eclampsia may not be predicted by maternal history and risk factors alone, especially in nulliparae. 6 Assessing its development is a primary focus of routine antenatal care and is responsible for many referrals to pregnancy day-stay units and antenatal admissions to hospital. As such, improving the prediction of pre-eclampsia has been the focus of a significant amount of research, both in asymptomatic populations at various gestations with varying a priori risk (ie screening), and for the prediction of the disease in patients in whom pre-eclampsia is suspected (ie diagnosis). This paper focuses on screening the performance of predictive tests for pre-eclampsia, the rationale for such tests and their integration into anticipated changes in early pregnancy management. The Rationale for Prediction The criteria a condition must meet to justify screening are well established and have remained essentially unchanged since first proposed by Wilson and Jungner 7 in 1968; these criteria are listed in Table 1. Whether pre-eclampsia yet meets these criteria continues to be the subject of debate, particularly regarding the effectiveness of prophylactic interventions, the absence of an effective treatment for established disease other than delivery and the performance of currently available testing strategies. 8,9 With respect to prevention, the benefit of aspirin in preventing pre-eclampsia among women at an increased risk of this condition has been the subject of a Cochrane review 10 (46 trials, 32,891 women), which found a relative risk of 0.83 (95% confidence interval 0.77–0.89), corresponding to a number needed to treat (NNT) of 72 to prevent one case of pre-eclampsia. Subsequently, the Perinatal Antiplatelet Review of International Studies (PARIS) collaborators published a meta-analysis of individual patient data 11 from 32,217 women, which identified a relative risk of 0.90 (95% confidence interval 0.84–0.97) and a number needed to treat of 114 (for a population in which 8% developed pre-eclampsia). Both studies also found statistically significant reductions in preterm birth. Numerous studies have assessed the impact of the gestational age at which aspirin is commenced. A meta- analysis from 2010 found a relative risk of pre-eclampsia among high-risk women of 0.47 (95% confidence interval 0.34–0.65, NNT 9) when aspirin is started at 16 weeks or earlier; when started later, the benefit was not significant (relative risk 0.81, 95% confidence interval 0.63–1.03). 12 Correspondence: Dr Stefan C. Kane, Department of Perinatal Medicine, The Royal Women’s Hospital, 20 Flemington Road, Parkville, Vic. 3052, Australia. Email: Stefan.Kane@thewomens.org.au Received 30 April 2013; accepted 9 October 2013. © 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists 1 Australian and New Zealand Journal of Obstetrics and Gynaecology 2013 DOI: 10.1111/ajo.12151 Te Australian and New Zealand Journal of Obstetrics and Gynaecology