The management of hypertension in pregnancy has always relied on stratification of risk. This ranges from identifying those to target with prophylactic therapies, such as aspirin, to deciding who to admit, monitor and deliver. Historical clinical features and the traditional use of blood pressure and proteinuria assessment have not been ideal in terms of their clinical utility. A combination of false positive and false negative assessments leads to over management, and cases being missed. Our increasing understanding of the pathophysiology of the disease has now resulted in angiogenic markers such as soluble flt and placental growth factor.
A role for angiogenic biomarkers in the diagnosis of pre-eclampsia is emerging. Currently, diagnosis relies on parameters associated with end-organ complications of established disease. Angiogenic factors are implicated in the pathophysiology of pre-eclampsia, which may have the potential of identifying women earlier in their disease course, or with more timely diagnosis. Low maternal Placental Growth Factor (PlGF) concentrations (defined as below the 5th centile for gestation or ≤100pg/ml) have demonstrated high sensitivity (0.96, 95% CI 0.89-0.99) and a negative predictive value (0.98, 95% CI 0.93-0.995) for predicting the development of pre-eclampsia that requires delivery within 14 days. These very low PlGF concentrations were often seen weeks prior to diagnosis of pre-eclampsia in this cohort. The PROGNOSIS study by Zeisler et al, 2016 was a prospective, multicenter observational study of 500 women, which demonstrated that an sFlt-1:PlGF ratio cutoff of 38 has clinical utility.29 Values below this have cutoff have high negative predictive value of 99.3% (95% CI 97.9-99.9), with 80% sensitivity (95% CI, 51.9-95.7) and 78.3% specificity (95% CI, 74.6-81.7). The positive predictive value of an sFlt-1:PlGF ratio above 38 for a diagnosis of preeclampsia within 4 weeks was 36.7% (95% CI, 28.4 to 45.7), with 66.2% sensitivity (95% CI, 54.0 to 77.0) and 83.1% specificity (95% CI, 79.4 to 86.3). The authors propose that in women in whom PET is suspected clinically, an sFlt-1:PLGF ratio of less than 38 can be used to rule out the short-term development of the syndrome
The most likely area of clinical impact for PlGF is in ‘point of care’ testing in women posing a diagnostic challenge to the clinician. These ‘point of care’ tests could have a substantial impact on health resource use, avoiding unnecessary admissions for those who will have a more benign disease course and a longer ‘time to delivery’ interval. A cost saving analysis performed in 2010 showed that the addition of an angiogenic biomarker test can amount to a saving of £945 per woman due to its ability to reduce the rates of false-positive and false-negative diagnoses compared to current standard of care. Such tests have the potential to assist in risk stratification in women at high risk of developing pre-eclampsia, singling out those with low PlGF to receive intensive surveillance to avoid adverse outcomes such as fetal demise. The PARROT study is underway to determine if the addition of PLGF testing to current management of women with pre-eclampsia will reduce the time taken to reach diagnosis, and thus improve maternal and perinatal outcomes.