The EMMA Study and Clinic (Evaluating Maternal and fetal Markers of Adverse placental outcomes)
As there is no single test that predicts pre-eclampsia (or the other placental complications of pregnancy, namely gestational hypertension, intrauterine growth restriction [IUGR], abruption, stillbirth and, probably, a substantial proportion of spontaneous preterm birth) with sufficient accuracy to be clinically useful, interest has grown around the development of multivariable models that include both clinical and laboratory predictors, available at booking and thereafter in pregnancy. Women at increased risk of pre-eclampsia may benefit from this type of risk stratification provided through a specialised clinic.
There is the potential to integrate discovery science into such a clinical activity, to develop models that include biomarkers on the cusp of being introduced into clinical care, as well as biomarkers more remote from that transition.
The EMMA Clinic, and its associated academic activity, was started in 2004, in response to a CIHR grant, with this combined remit of advising direct clinical care with extant knowledge, as well as improving future outcome prediction.
Using a consultation-only model, with very occasional retention of women in the MFM Clinic structure (primarily if suffering from early-onset IUGR), women are seen in the EMMA Clinic from as early as 15 weeks gestation. Blood for any outstanding maternal serum markers are drawn, and the results interpreted in conjunction with uterine artery Doppler findings. These findings are interpreted using a predetermined paradigm (Table).
Building on the experience and protocols of the Silver Star Clinic, John Radcliffe Hospital, Oxford, UK, women stratified to differing levels of risk are entered into stratified follow-up. Caregivers for women in the high risk stratum (≥60% risk of placental complications) receive a suggestion to initiate fortnightly follow-up that includes serial growth, fluid and umbilical artery ultrasound scans and blood work to exclude pre-clinical pre-eclampsia. Women in the intermediate risk group (30-59% risk) are advised to receive 4-weekly clinical, ultrasound and blood work assessment, while EMMA Clinic-eligible women determined to be at lower risk (<30%) are advised to receive a single additional growth ultrasound in the early third trimester.
With clinical data on approximately 800 women who have attended the clinic and for whom we have follow-up information until delivery, we are assessing the performance of the clinic in terms of accuracy of risk stratification, and the independent performance of clinical, ultrasound and laboratory assessments within a multivariable model. In addition, with pre-disease samples for approximately 200 women, we are assessing the roles of a series of hypothesis-generated biomarkers in this setting.
Interim results show that risk stratification is possible in this cohort of higher risk women, and that outcomes vary by risk stratum. Also, we are assessing the outcomes for this cohort of women compared with non-attenders with similar risk factors through collaboration with Drs Amy Metcalfe, KS Joseph and Sylvie Langlois.
In addition, we have assessed the prediction performance of a series of biomarkers within this enriched cohort, and determined that some biomarkers have additional stratification value compared with more established risk stratification criteria.