Biomarkers in the early prediction of preeclampsia and related disorders

Abstract

Hypertensive disorders of pregnancy are among the leading causes of maternal and perinatal morbidity and mortality worldwide, and their early prediction remains a key challenge in contemporary obstetric medicine. The objective of this study was to identify and synthesize evidence from prospective studies published between 2021 and 2025 that evaluated biomarkers for the early prediction of these disorders. A systematic review was conducted following PRISMA 2020 guidelines, with a structured search in PubMed using a comprehensive algorithm combining MeSH descriptors and free-text terms related to preeclampsia, biomarkers, early prediction, and prospective studies, limited to articles in English and Spanish. From a total of 535 records, 12 studies met the eligibility criteria and were included for qualitative synthesis. The identified biomarkers spanned various categories, including biochemical (NT-proBNP, sortilin, TyG index), inflammatory (hs-CRP, neuroserpin), angiogenic (sFlt-1/PlGF ratio), genetic (salivary cfRNA), and imaging-based (uterine artery Doppler, Fetal HQ technology). These studies demonstrated variable but significant predictive capacities, with multimodal models combining biomarkers and clinical factors yielding the best results. The findings confirm that multiple biomarkers can anticipate the onset of preeclampsia and other hypertensive pregnancy complications with acceptable levels of sensitivity and specificity, particularly when integrated into personalized models. It is concluded that the incorporation of validated biomarkers into clinical protocols adapted to specific healthcare settings can improve risk stratification and optimize perinatal decision-making. Further multicenter validation and standardization of these tools are recommended to support their widespread clinical implementation.