National organizations, including the ACOG, typically do not include the use of biomarkers in their practice guidelines for the diagnosis and identification of women with preeclampsia (PE). Other organizations, such as the Preeclampsia Foundation (PF), are investigating the usage of biomarkers for more advanced diagnosis of PE. Recently, the PF gathered together nine diagnostic companies and several leading clinicians and researchers in the field of preeclampsia to discuss future biomarkers for diagnosing and screening for the risk of PE. At present, most, if not all, healthcare insurers consider testing for biomarkers to diagnose PE as experimental and investigational.
The following conclusions can be made regarding the clinical use of biomarkers to identify and diagnose PE:
- Although the identification of certain biomarkers may hold promise in the early detection of patients with a greater risk of PE, none of the aforementioned biomarkers appear to have sufficiently high positive predictive value when used alone.
- A combination of biomarkers appears to be more useful than a specific individual biomarker. For example, a combination of PlGF, sFlt-1, sEng, VEGF, and sFlt-1/PlGF ratio tend to have stronger predictive value for PE. Although the use of a combination of biomarkers may improve upon the clinical utility for predicting PE, more studies are needed to confirm their clinical use to specifically predict PE. There is a lack of validation studies for these biomarkers and a lack of agreement on the cut-off points or standardization points to determine abnormal levels.
- Recently, the FDA issued approval to Thermo Scientific for their sFlt-1 and PlGF test system, which measures the serum or plasma levels of the two biomarkers, PlGF and sFlt-1, and expresses the results as the sFlt-1/PlGF ratio. The test yields a risk stratification ratio, which determines whether a pregnant woman would be a candidate to benefit from enhanced surveillance and accelerated care before severe PE features develop.
This new FDA-approved biomarker assay system is intended to be used along with other laboratory tests and clinical assessments to aid in the risk assessment of pregnant women.
- The addition of Doppler Ultrasonography of the uterine arteries with the biomarker combinations may improve upon the predictability of PE. However, more studies to confirm the clinical utility of Doppler ultrasonography need to be performed.
- There is a lack of the understanding of the precise cause(s) of PE and the progression of PE does not give us a clear indication on definitive treatment interventions.
- Most national professional organizations do not yet recommend biomarker testing for the diagnosis of PE.
- There is no consensus at this point among clinicians and obstetricians on the clinical acceptance for the use of biomarkers in the risk assessment and diagnosis of PE.
- Most major insurers consider biomarker testing to assess PE as experimental and investigational.