Preeclampsia (PE) remains a complex, multisystem disorder, with clinical manifestations that often appear late in the disease course.¹ At the 5^th Malaysian Obstetric Medicine Scientific Conference, Dr. Tan Lay Kok from KK Women’s and Children’s Hospital, Singapore, highlighted how placental biomarkers are enabling earlier prediction and preemptive management of PE.¹

PE is widely understood to follow a two-stage process.¹ Abnormal placentation occurs early in pregnancy, with impaired trophoblastic invasion of the spiral arteries resulting in placental hypoxia and dysfunction.¹ This precedes the release of placental markers into the maternal circulation, triggering systemic endothelial inflammation and the maternal and fetal syndromes of PE.¹ “Preeclampsia is not just hypertension,” Dr. Tan noted. “By the time blood pressure rises or proteinuria appears, we are already seeing downstream effects of placental disease.”

Central to this process is an angiogenic imbalance.¹ In healthy pregnancies, angiogenic factors such as placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) support normal placental vascular development.¹ In PE, placental-derived anti-angiogenic factors, particularly soluble fms-like tyrosine kinase-1 (sFlt-1), rise prematurely, while PlGF levels fall.¹ This imbalance reflects placental stress and is closely associated with disease severity, with elevated sFlt-1/PlGF ratios signaling poorer prognosis.¹

Unlike conventional clinical markers, placental biomarkers offer insight into disease biology before overt symptoms emerge.¹ In normal pregnancy, PlGF levels rise through mid-gestation before declining toward term, mirroring placental maturation. In PE, low PlGF can be detected weeks before clinical presentation.¹ “What we routinely measure—blood pressure and proteinuria—are tertiary features,” Dr. Tan explained. “Placental biomarkers allow us to go upstream, and that has implications for prevention and care.”

Evidence supporting early screening with placental biomarkers was extensively discussed.¹ Findings from the ASPRE study demonstrated substantial risk reductions in preterm and early-onset PE through first-trimester screening combined with targeted preventive intervention.¹ These data support universal screening at 11-14 weeks’ gestation, enabling early identification of high-risk women and timely initiation of preventive strategies with aspirin. 

Placental biomarkers also play a key role in the evaluation of suspected PE, particularly in complex clinical settings.¹ Diagnostic uncertainty is common in women with chronic hypertension, renal disease, diabetes with nephropathy, or systemic lupus erythematosus, as well as in pregnancies complicated by fetal growth restriction.¹ In such scenarios, PlGF testing has shown strong clinical validity.¹ Prospective studies, including PELICAN and PETRA, reported high sensitivity and negative predictive value for low PlGF levels in predicting the need for delivery within a short timeframe, outperforming traditional clinical parameters.¹

Randomized evidence further supports clinical utility.¹ In the PARROT trial, PlGF-guided care reduced time to diagnosis and was associated with fewer severe maternal adverse outcomes.¹ Low PlGF consistently identified a more severe disease phenotype, prompting closer surveillance and earlier intervention without increasing preterm delivery rates.¹

For clinical implementation, a traffic-light approach to PlGF interpretation provides practical guidance.¹ Highly abnormal levels (<12pg/mL) indicate severe placental dysfunction and a high likelihood of imminent delivery, often warranting hospitalization.¹ Intermediate levels suggest placental dysfunction and the need for increased surveillance, while normal levels (100pg/mL) effectively rule out progression to PE requiring delivery in the near term.¹ “A normal PlGF buys us time,” Dr. Tan observed, even among women who ultimately develop PE.

The session also addressed the role of the sFlt-1/PlGF ratio, which has demonstrated excellent short-term rule-out performance.¹ Data from the PROGNOSIS and PROGNOSIS Asia studies showed high negative predictive value when ratios are low, allowing clinicians to safely defer intensive intervention, while higher ratios identify women at increased risk of PE or adverse outcomes.¹

In summary, placental biomarkers extend beyond diagnosis to enable earlier prevention, clearer risk stratification, and more targeted care.¹ “Placental pathophysiology leaves a signature in the maternal circulation,” Dr. Tan concluded. “If we detect it early, we can intervene earlier, improving outcomes for both mother and baby.”¹

In an interview with Omnihealth Practice, Dr. Tan Lay Kok discussed how placental biomarkers are transforming preeclampsia care by enabling earlier prediction, clearer risk stratification, and more proactive management.

Q1: In your clinical practice, which patients stand to benefit most from placental biomarker testing for preeclampsia?

Dr. Tan: Ideally, all pregnant women should be offered screening in the first trimester, between 11-14 weeks. Incorporating this test into routine early pregnancy bloodwork adds minimal burden, yet it fills a major clinical gap. Traditional risk assessment using clinical markers detects only a fraction of women who will develop preeclampsia. With universal placental biomarker testing, at-risk patients can be identified early, when preventive strategies such as low-dose aspirin are most effective.

Q2: Are there practical barriers to implementing placental biomarker screening?

Dr. Tan: Barriers are relatively modest. Placental biomarkers involve an extra blood test, which most labs can validate using existing data. The main requirement is a structured workflow: once a high-risk result is identified, there must be a system to review results, follow up with patients promptly, and initiate preventive measures. Screening alone is not enough; timely intervention, such as starting aspirin before 16 weeks, is key to reducing preeclampsia risk.

Q3: How do placental biomarkers change the way women at risk of preeclampsia are monitored and managed?

Dr. Tan: Biomarkers shift care from reactive to proactive. In early pregnancy, they guide preventive strategies. Later, in suspected or atypical preeclampsia, PlGF and sFlt-1/PlGF ratios help confirm diagnosis and stratify risk. This informs surveillance intensity, hospitalization decisions, steroid use, referrals to higher-level centers, and timing of delivery. Normal biomarker results provide reassurance and may safely prolong pregnancy. Overall, their use supports targeted, efficient care and can improve maternal and neonatal outcomes.