Photo Credit: Svitlana Hulko
Preeclampsia remains a significant contributor to maternal morbidity and mortality, affecting 2% to 8% of pregnancies worldwide. Given the potential for severe complications, there is a pressing need for effective screening methods. However, despite recent advancements in biomarker testing, concerns persist regarding the clinical utility of these tools.
“Preeclampsia is a condition that often has an insidious onset and protean manifestations. I often call the disease ‘The Great Imitator’,” says Dr. Kecia Gaither, Director of Perinatal Services/Maternal Fetal Medicine at NYC Health + Hospitals/Lincoln, emphasizing the complexity of diagnosing the condition.
The rapid adoption of screening tests without robust evidence of their impact on patient outcomes raises critical questions about their role in clinical practice.
The Two-Step Process of Screening Tests
The development and implementation of a new screening test should follow a two-step process. First, a test must demonstrate its ability to predict a specific outcome or effectively stratify patients by risk. Second, and more importantly, there must be evidence proving that the test improves clinical outcomes. Many preeclampsia screening tests have cleared the first hurdle but have yet to establish clinical utility.
Despite this, the Food and Drug Administration (FDA) has approved several preeclampsia screening tests based solely on predictive capability, allowing them to enter clinical practice without clear evidence that they improve maternal or neonatal health outcomes. This raises concerns about premature adoption and the potential for unintended consequences. “To date, there is no set universal laboratory-based screening modality for the disease,” Dr. Gaither explains, highlighting the gap in standardized screening protocols.
Study Methods and Findings
Recent research has focused on identifying biomarkers that can aid in the diagnosis and risk assessment of preeclampsia. One promising approach involves measuring placental growth factor (PlGF) and the sFlt-1:PlGF ratio. Studies have shown that lower levels of PlGF and elevated sFlt-1:PlGF ratios correlate with a shorter time to delivery and a higher likelihood of adverse outcomes. However, while these tests demonstrate strong negative predictive value (NPV), their positive predictive value (PPV) remains low to moderate, meaning they may over-identify patients at risk without clear benefits in treatment interventions.
A recent FDA-approved test, the BRAHMS sFlt-1/PlGF KRYPTOR Test System, was granted approval based on a study funded by its manufacturer. This test effectively identifies patients at high risk for developing severe preeclampsia within two weeks. However, its clinical application remains uncertain, as it has not been definitively proven to alter management strategies or improve maternal and neonatal outcomes.
“With the advent of a universal laboratory-based screening modality like sFlt-1, there will exist a faster, specific identification of those at risk, with subsequent improved perinatal outcomes given this heightened recognition,” says Dr. Gaither.
One of the most significant risks of widespread implementation without proven clinical utility is “indication creep.” Over time, clinicians may expand the use of screening tests beyond their original intended population, potentially leading to unnecessary interventions, increased hospitalizations, and heightened patient anxiety. Additionally, over-reliance on these tests may result in an increase in preterm deliveries due to heightened caution, thereby inadvertently contributing to neonatal morbidity.
Implications and Limitations
International guidelines reflect varying perspectives on these tests. The National Institute for Health and Care Excellence (NICE) in the UK has endorsed the sFlt-1:PlGF ratio as a diagnostic aid for preeclampsia, despite its moderate PPV. Conversely, the American College of Obstetricians and Gynecologists (ACOG) has issued more cautious guidance, emphasizing that these tests should be used only for patients meeting strict inclusion criteria.
The rapid regulatory approval of preeclampsia screening tests highlights a fundamental issue in the evaluation of diagnostic tools. Unlike pharmaceuticals, which require rigorous randomized controlled trials (RCTs) to prove clinical efficacy, diagnostic tests often reach the market without comparable validation. Moving forward, the medical community must demand high-quality evidence demonstrating that these tests lead to better maternal and neonatal outcomes before integrating them into routine practice.
Screening tests should enhance, not merely expand, clinical decision-making. While advancements in biomarker research offer promising pathways, their implementation should be grounded in clear, evidence-based benefits.
“Having a defined universal laboratory screening modality for this disease will ultimately reduce the cost of care for the maternal-fetal dyad by identifying those at risk, and potentially obviating some of the more catastrophic clinical complications of the disease, like stroke, cardiovascular decompensation, liver rupture, or placental abruption,” Dr. Gaither stresses.
Until then, physicians must remain cautious in relying on these tools to guide patient management.
Findings Summary
Findings suggest that preeclampsia screening tests must undergo rigorous evaluation to ensure they improve patient outcomes. Without clear evidence of clinical utility, their premature adoption may lead to unintended consequences, including unnecessary interventions and increased healthcare costs.
“As a Maternal Fetal Medicine Specialist, I see preeclampsia all day, every day, with all of the various, often subtle protean manifestations. I think the sFlt-1 screening for the disease would be a huge boon to the obstetric world as a tool to effect better perinatal outcomes,” Dr. Gaither concludes.
The medical community must prioritize randomized trials and outcome-based research before integrating these tools into routine practice.
