THE IMPORTANCE OF MODERN BIOMARKERS IN THE EARLY DETECTION AND PREVENTION OF PREECLAMPSIA
4th-year student, Group Med-01U
Faculty of Medicine
Kimyo International University in Tashkent
Abstract: Preeclampsia is a multifactorial obstetric syndrome that develops during the second half of pregnancy and increases the risk of serious maternal and fetal complications. Because clinical manifestations often appear after the pathological process has already progressed, early detection remains an important area of modern obstetrics. In recent years, biomarkers reflecting placental angiogenic activity, particularly placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and their ratio, as well as pregnancy-associated plasma protein A (PAPP-A), placental protein 13 (PP13), and other laboratory parameters, have been extensively investigated. This article reviews the pathogenesis of preeclampsia, the biological basis of relevant biomarkers, their diagnostic and prognostic significance, and their potential role in clinical practice. According to contemporary international recommendations, combined assessment of clinical risk factors, blood pressure, uterine artery pulsatility index, and PlGF in the first trimester can be used for risk stratification of preterm preeclampsia. In pregnancies at 20–36+6 weeks with suspected preeclampsia, PlGF-based or sFlt-1/PlGF-based tests may provide additional information to clinical assessment. However, biomarkers have limitations in predicting all cases of preeclampsia and should not be interpreted as independent diagnostic criteria.
Keywords: preeclampsia; pregnancy; biomarker; placental growth factor; PlGF; sFlt-1; sFlt-1/PlGF; PAPP-A; placenta; angiogenesis; early diagnosis; obstetrics.
INTRODUCTION
Preeclampsia is one of the major hypertensive disorders of pregnancy and may have serious consequences for maternal and fetal health. Clinically, it may present with hypertension accompanied by dysfunction of the kidneys, liver, hematological system, central nervous system, or placenta. Severe cases may be complicated by eclampsia, HELLP syndrome, placental abruption, fetal growth restriction, preterm birth, and adverse perinatal outcomes.
An important feature of preeclampsia is that pathological changes in placentation and the maternal vascular system may develop before clinical manifestations become apparent. Therefore, an approach based only on blood pressure and proteinuria may be insufficient for detecting the earliest stages of the disease.
In recent years, the role of biomarkers in the detection of preeclampsia has been extensively investigated. In particular, angiogenic and antiangiogenic factors such as PlGF and sFlt-1 have attracted substantial scientific interest.
RELEVANCE OF THE TOPIC
The relevance of preeclampsia is associated with its potential risks to the mother and fetus, its heterogeneous clinical course, and the difficulty of predicting the disease before clinical manifestations appear.
Traditional clinical assessment includes blood pressure, urinary protein, platelet count, liver and kidney function, and fetal status. However, disruption of placental angiogenic balance may occur before clinical signs become evident.
Therefore, the use of biomarkers to identify pathological processes before clinical manifestations is a promising area of modern obstetrics.
AIM OF THE STUDY
To analyze the biological and clinical significance of modern biomarkers used for early detection and risk assessment of preeclampsia, evaluate their advantages and limitations, and describe their potential role in obstetric practice.
MATERIALS AND METHODS
This article was prepared as a literature review. Scientific information was identified using PubMed, clinical recommendations from international professional organizations, and medical guidelines.
The review included systematic reviews, meta-analyses, and clinical recommendations addressing early detection of preeclampsia, angiogenic biomarkers, PlGF, sFlt-1, the sFlt-1/PlGF ratio, PAPP-A, PP13, first-trimester screening, and prediction of preeclampsia risk.
Particular attention was given to contemporary sources published during 2021–2026, while earlier fundamental studies were also considered where necessary to explain the biological significance of biomarkers.
PATHOGENETIC BASIS OF PREECLAMPSIA
Impaired placental invasion and abnormal uteroplacental circulation play important roles in the development of preeclampsia. In normal pregnancy, trophoblast cells remodel the uterine spiral arteries, transforming them into vessels capable of providing adequate blood flow.
In preeclampsia, this remodeling may be incomplete. As a result, placental hypoxia, oxidative stress, and endothelial dysfunction may develop.
Subsequently, placental production of angiogenic and antiangiogenic factors changes. In particular, increased sFlt-1 and decreased PlGF adversely affect normal endothelial function.
sFlt-1 binds PlGF and vascular endothelial growth factor, reducing their biological activity. This contributes to impaired angiogenesis and endothelial stability and plays an important role in the development of hypertension, proteinuria, and multiorgan dysfunction in preeclampsia.
PLACENTAL GROWTH FACTOR — PlGF
Placental growth factor is a proangiogenic protein involved in angiogenesis. During normal pregnancy, its concentration changes according to gestational age.
In preeclampsia, placental dysfunction may lead to reduced PlGF concentrations. Therefore, PlGF has been investigated as an important biomarker of placental dysfunction in preeclampsia.
However, PlGF should not be interpreted in isolation. Gestational age, clinical condition, and laboratory methodology may affect the result.
sFlt-1 BIOMARKER
Soluble fms-like tyrosine kinase-1 is an antiangiogenic factor that plays an important role in the pathogenesis of preeclampsia.
sFlt-1 binds PlGF and vascular endothelial growth factor and reduces their vascular protective effects. Consequently, endothelial dysfunction increases.
Increased sFlt-1 concentrations have been reported in numerous studies of preeclampsia. Therefore, combined assessment of sFlt-1 and PlGF may provide more clinically useful information than either biomarker alone.
sFlt-1/PlGF RATIO
The sFlt-1/PlGF ratio is one of the most extensively studied angiogenic markers in modern preeclampsia assessment. It reflects two opposing biological processes: increased antiangiogenic activity and decreased proangiogenic activity.
NICE recommendations provide gestational-age-specific thresholds for the Elecsys sFlt-1/PlGF test. At 20–33+6 weeks, a value of 33 or lower can be used to help rule out preeclampsia, whereas a value above 85 can support the diagnosis. From 34 weeks to delivery, the corresponding thresholds are 33 and 110.
At 24–36+6 weeks, an sFlt-1/PlGF ratio of 38 or lower can help rule out development of preeclampsia in the short term, while a value above 38 can help assess the risk of developing preeclampsia within the following four weeks. These thresholds should be interpreted according to the relevant test system and clinical context.
SIGNIFICANCE OF PAPP-A
Pregnancy-associated plasma protein A is a laboratory marker widely used in first-trimester prenatal screening.
A recent meta-analysis included 22 studies and data from 33,651 pregnant women. It found that first-trimester PAPP-A concentrations were lower among women who subsequently developed preeclampsia compared with controls. The authors considered PAPP-A a potentially useful marker for early risk stratification of preeclampsia.
Nevertheless, PAPP-A alone does not have sufficient accuracy to diagnose preeclampsia. It is more appropriately interpreted together with clinical and ultrasound parameters.
PLACENTAL PROTEIN 13
Placental protein 13 has also been investigated as a potential early biomarker of preeclampsia.
A meta-analysis of 17 observational studies including 40,474 pregnant women reported a pooled sensitivity of 0.62 and specificity of 0.84 for PP13. These findings indicate potential value, but large prospective studies are still needed before routine clinical implementation.
COMBINED FIRST-TRIMESTER SCREENING
The ability to predict preeclampsia using a single biomarker is limited. Therefore, contemporary approaches emphasize multicomponent risk assessment.
ISSHP recommendations indicate that, at 11–14 weeks, clinical risk factors, blood pressure, uterine artery pulsatility index, and PlGF may be combined to assess the risk of preterm preeclampsia. At the same time, no first- or second-trimester test can reliably predict all cases of preeclampsia.
A combined approach can therefore be summarized as: maternal characteristics + blood pressure + uterine artery Doppler + PlGF → individualized risk assessment.
CLINICAL ROLE OF BIOMARKERS
The main purpose of biomarkers in preeclampsia is not simply to determine whether disease is present. They may help identify women at increased risk, assess the probability of preeclampsia in clinically suspicious cases, estimate short-term risk, support decisions about monitoring intensity, and in some settings reduce unnecessary inpatient observation.
According to NICE, PlGF-based tests used together with standard clinical assessment can help rule in or rule out preterm preeclampsia in women with suspected disease.
LIMITATIONS OF BIOMARKERS
Despite their promising potential, modern biomarkers cannot be regarded as universal diagnostic tools. First, biomarker concentrations depend on gestational age. Second, analytical methods and thresholds may differ between laboratory systems. Third, multiple pregnancy, chronic hypertension, kidney disease, and other clinical conditions may influence biomarker concentrations.
Although many promising biomarkers are being investigated, large prospective studies and external validation are required before their clinical utility can be fully established.
DISCUSSION
Early detection of preeclampsia cannot be reduced to identifying a single laboratory biomarker. The multifactorial pathogenesis of the disease requires assessment of several biological processes.
PlGF and sFlt-1 currently have substantial clinical relevance among angiogenic biomarkers, and their ratio may be particularly useful for assessing the probability of preeclampsia.
In the first trimester, combining clinical risk factors, blood pressure, uterine artery Doppler, and PlGF may improve risk stratification for early-onset disease. However, this approach cannot identify every case of preeclampsia.
Future research may focus on integrating biomarkers with artificial intelligence, clinical risk factors, ultrasound data, and genetic or metabolic parameters. Before such models are introduced into routine practice, external validation in diverse populations and assessment of clinical utility are required.
RESULTS
The literature review yielded the following main findings:
1. Placental angiogenic imbalance may develop before the clinical onset of preeclampsia.
2. Reduced PlGF and increased sFlt-1 are associated with the pathophysiology of preeclampsia.
3. The sFlt-1/PlGF ratio may be clinically useful for assessing short-term risk in women with suspected preeclampsia.
4. PAPP-A and PP13 are promising biomarkers under investigation for first-trimester risk assessment, but evidence is insufficient to use them as independent diagnostic tools.
5. Combined assessment of clinical risk factors, blood pressure, uterine artery Doppler, and PlGF provides a more comprehensive risk stratification approach.
6. Biomarkers cannot completely replace clinical examination, blood pressure monitoring, urine testing, and assessment of fetal status.
7. Contemporary international recommendations emphasize the use of biomarkers together with clinical assessment.
CONCLUSION
Early detection of preeclampsia is an important component of modern obstetric strategies aimed at reducing maternal and fetal complications. Placental dysfunction and imbalance between angiogenic and antiangiogenic factors play important roles in the pathogenesis of preeclampsia.
PlGF, sFlt-1, and the sFlt-1/PlGF ratio are among the most extensively studied biomarkers reflecting these pathological processes. PAPP-A and PP13 remain promising areas for first-trimester risk assessment.
Preeclampsia cannot be fully predicted using a single biomarker. The most appropriate approach is an integrated assessment of clinical risk factors, blood pressure, uterine artery Doppler findings, and laboratory biomarkers.
PRACTICAL SIGNIFICANCE
Early identification of women at risk of preeclampsia can support individualized antenatal surveillance. In women with clinical risk factors, early risk assessment, intensified follow-up, and biomarker testing when clinically indicated may be appropriate.
At 20–36+6 weeks, in pregnancies with suspected preeclampsia, PlGF- or sFlt-1/PlGF-based tests may provide additional information to clinical assessment. Test results should always be interpreted together with the woman’s overall clinical condition.
References
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Sevinch Rustamova Shuxrat qizi was born on October 13, 2005, in Muborak District, Kashkadarya Region, Uzbekistan. She is currently a fourth-year student at Kimyo International University in Tashkent, studying General Medicine in the Med-01U group.
Alongside her medical education, Sevinch has a deep passion for poetry and creative writing. She has participated in several international Olympiads and literary projects. Her poems and creative works have been published in international anthologies in Egypt and Qatar.
In 2025, she also participated in an international literary anthology in Türkiye, where she presented her creative works and delivered a speech on an international platform. Her scientific articles and theses have been published in various reputable scientific journals, and she actively participates in national conferences, academic forums, and scholarly events.
Sevinch combines her interests in medicine, science, poetry, and literature, aspiring to contribute to both the scientific and cultural spheres through her knowledge, creativity, and continuous pursuit of personal and professional development.