Maternal and fetal health diagnostics: The case for advancing preeclampsia screening

Current maternal and fetal health diagnostics — more commonly referred to as prenatal care — have their roots in the late 1800s and early 1900s. During this time, physicians began to gain insights into what is now known as preeclampsia or eclampsia (“toxemia”), identifying hypertension as an early indicator of the condition.¹ These discoveries laid the foundation for future prenatal interventions. The primary goal of prenatal care, “to have the pregnancy end with a healthy baby and mother,” has remained unchanged for over a century.

Current practices and persistent challenges

Today, by identifying risk factors for pregnancy complications and maternal health concerns, healthcare providers aim to optimize pregnancy outcomes. Through a combination of screening and diagnostic tests, along with serial monitoring of physical examination components, providers assess the ongoing health of the pregnancy. While the ability to screen and intervene has improved significantly over the past century, and the scope of assessments has expanded, the prevalence of preeclampsia—the condition that originally prompted the development of prenatal care—has not decreased.²

Global impact of preeclampsia

Preeclampsia affects approximately 10 million pregnancies worldwide each year resulting in 2.5 million babies born prematurely.^3,4 In the United States, its prevalence has been increasing.⁵ Despite advances in medical interventions, we continue to invite women to maternity visits to detect the same conditions as we did a century ago.⁶ In high-income countries, current medical interventions can save most mothers and babies, while in low-income countries, many still die from this condition.⁴

Understanding preeclampsia: Risks, symptoms, and consequences of preeclampsia

Preeclampsia can affect any pregnancy. The clinical symptoms that define preeclampsia —hypertension and maternal organ failure (including proteinuria) — are not always perceptible. Other symptoms may include upper abdominal pain, vomiting, severe headaches, and visual disturbances, which can be difficult to identify. As a result, preeclampsia can progress rapidly into a life-threatening state. If it develops before 37 weeks of gestation, early delivery is often necessary, resulting in premature birth. Both mother and baby are affected, even if they survive. Prematurity can have long-term consequences for the baby’s health and development, and mothers who experience preeclampsia are at increased risk for chronic diseases such as cardiovascular disease and diabetes mellitus later in life. Therefore, better means to improve maternal and neonatal outcomes are essential.⁷

Advancements in prediction and management

Over the past two decades, significant progress has been made in developing tools to predict and manage pregnancies at risk for preeclampsia. Since the early 2000s, innovations in preeclampsia testing—driven by global collaboration among experts in obstetrics and gynecology and industry — have led to the identification of biomarkers that predict adverse pregnancy outcomes related to poor placental function, including preterm preeclampsia.^8,9,10

Placental growth factor (PlGF) and its role: Impactful studies and evidence

Placental growth factor (PlGF) is a protein found in low concentrations in maternal blood during pregnancy. When there is a risk of preeclampsia, PlGF levels are even lower. Highly sensitive PlGF assays have been developed to maximize detection rates using first-trimester prediction protocols.¹¹

PlGF-based assays have been used in milestone studies such as ASPRE, which demonstrated the performance of the competing screening model by the Fetal Medicine Foundation to identify women at high risk for placental insufficiency-related conditions like preterm preeclampsia. This study also showed the efficacy of aspirin prophylaxis. The ASPRE randomized controlled trial demonstrated an 89% reduction in preeclampsia before 32 weeks and a 62% reduction before 37 weeks, along with a 70% decrease in neonatal intensive care stays for babies born before 32 weeks—highlighting the impact of early detection.^{12, 13} The SPREE study showed that screening performance improves significantly when biomarkers like PlGF are used alongside maternal factors, which are currently recommended by ACOG (US) and NICE (UK).¹⁴ PlGF has also shown value as a marker for fetal growth restriction and stillbirth.^{15, 16} The performance of the FMF competing screening model has been replicated in many local and national studies globally, showing its superiority over standard care practices based on maternal factors alone.

Timing of screening and preventive actions

PlGF-based screening is performed at early pregnancy, between 11–14 weeks of gestation. Timing is critical, as starting low-dose aspirin prophylaxis treatment before 16 weeks—ideally before 14—is essential for maximum effectiveness. Testing after this window can still provide insights into placental function, but preventive actions are limited to monitoring and managing the condition if it develops.^12, 13

Early identification of at-risk pregnancies is key to reducing both short- and long-term adverse outcomes. As demonstrated by ASPRE and subsequent studies, the majority of severe preterm preeclampsia cases can be prevented.^{18, 19} Screening offers a significant opportunity to reduce healthcare costs while protecting the health of mothers and babies.²⁰

Diagnostic and monitoring applications

Beyond prediction and prevention, PlGF—alone or in combination with soluble fms-like tyrosine kinase-1 (sFlt-1)—can aid in diagnosis when symptoms arise and help monitor disease progression and severity. When time is critical, these markers can accelerate diagnosis and care, ultimately improving outcomes.^20-23

Implementation to current workflows

Looking beyond the clinical markers, the implementation of enhanced screening and aid in diagnosis with PlGF-based tools is straightforward. At a practical level, performing the screening is very similar to aneuploidy screening, which has been standard practice for decades. These models are usually supported by easy-to-use screening software that supports optimal workflows for both clinicians and laboratories. Aid in diagnosis does not differ from various clinical chemistry tests performed on a daily basis. Preeclampsia screening has been developed to integrate with existing infrastructures.^23-25

Barriers to adoption and the call for change

Despite strong clinical evidence, implementation of these tools remains slow. Concerns about performance, cost-effectiveness, prophylaxis, and insufficient evidence remain common arguments against adoption. It appears the decision makers as well as the medical community are waiting for a perfect solution or for others to take the lead. While further scientific evidence is needed to refine identification and management strategies, using available markers is the best way to learn how to maximize their potential. These tools do not increase pregnancy risk, even in cases of false positives—unlike aneuploidy screening.

Meanwhile, delays in implementation continue to affect women and babies. Those who survive may live with long-term consequences. Isn’t it time to make a change?

Conclusion: Time to act

The evidence is clear: early screening and intervention can save lives and improve outcomes. While further research will enhance these tools, starting to use them now is the best way to learn and refine their application—while saving lives and improving outcomes for mothers and babies.

References

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