Clinical risk prediction of pre-eclampsia
Authors: L. A. Magee, P. v. Dadelszen
Journal: BMJ (2011)

Pre-eclampsia remains a leading cause of maternal and perinatal mortality andmorbidity worldwide. In the linked study (doi:10. 1136/bmj.d1875), North and colleagues present a predictive model for pre-eclampsia that is based on routine clinical data. The study used data from 3529 “healthy” nulliparous women with a singleton pregnancy participating in the Screening for Pregnancy Endpoints (SCOPE) study. The SCOPE study is a large international undertaking that makes an important contribution towards assessing potential risk markers, individually and in combination. North and colleagues have identified nine clinical predictors of pre-eclampsia: one protective (miscarriage at ≤10 weeks’ gestation with the same partner) and eight associated with increased risk (younger maternal age, higher mean arterial blood pressure, higher body mass index, family history of pre-eclampsia, family history of coronary heart disease, the woman having a lower birth weight, vaginal bleeding for at least five days during early pregnancy, and duration of sexual relationship six months or less). All can be collected easily in routine clinical practice, and each of their associations with pre-eclampsia is consistent with the published literature. The SCOPE model has an area under the receiver operating curve (AUCROC) of 0.71 whether or not uterine artery Doppler data (bilateral notching or mean resistance index) are included. This AUC ROC is on the cusp of the threshold that defines a clinically useful test (0.70). The point of the AUC ROC curve that optimises sensitivity and specificity is associated with a false positive rate of 30-40%. Only about half of the women with pre-eclampsia would be detected using the information provided in the paper. In a healthy nulliparous woman, the pre-test probability of pre-eclampsia would be 5%. This figure would increase using the model proposed by North and colleagues, but only to 10%. Also, the model seems to underestimate pre-eclampsia at rates greater than 10%. It is questionable whether the most clinically relevant end points are prediction of “any pre-eclampsia” or “pre-eclampsia resulting in delivery at less than 37 weeks’ gestation.” It is increasingly clear that pre-eclampsia that develops early and results in delivery before 34 weeks’ gestation has a higher maternal mortality and morbidity than pre-eclampsia that develops later and results in delivery at or near term. 5 Further recruitment to the cohort may allow for sufficient numbers to evaluate early severe pre-eclampsia (with delivery at less than 34 weeks) as an end point, in addition to others, such as intrauterine fetal growth restriction or placental abruption. Importantly, North and colleagues did not include the results of first or second trimester serum screening, which can be used to stratify the risk of placental disease (such as pre-eclampsia or fetal growth restriction) without assessing the risk of aneuploidy in families not interested in prenatal diagnosis. Although the authors clearly state their future plan to include biomarkers that may improve the performance of the model, those markers collected in routine clinical practice should have been included in this initial pragmatic modelling study to reflect what clinicians have to work with at the present time. How should clinicians interpret these results? The authors wisely conclude that their model needs external validation before clinical application, and we agree. However, there are three important take home messages. Firstly, although all historical risk factors can be routinely collected and are supported by published data, three are less well known yet were found to be influential in North and colleagues’ model: family history of pre-eclampsia, family history of coronary heart disease, and vaginal bleeding for at least five days during early pregnancy. Secondly, the model cannot accurately predict who will not develop pre-eclampsia, so absence of the risk markers must not be used to justify a decrease in the intensity of antenatal care. Thirdly, North and colleagues’ model can identify some but not most of the woman who will develop pre-eclampsia. If one or more of the model’s risk factors is (are) identified in early pregnancy, the clinician could consider taking one or more of the following actions: providing specific education about the signs and symptoms of pre-eclampsia to facilitate early diagnosis, increasing materno-fetal surveillance, introducing low risk interventions that decrease the risk of pre-eclampsia in other “at risk” populations (such as low dose aspirin), or