Potential biomarkers for late-onset and term preeclampsia: A scoping review

Preeclampsia is a progressive, multisystem pregnancy disorder. According to the time of onset or delivery, preeclampsia has been subclassified into early-onset (<34 weeks) and late-onset (≥34 weeks), or preterm (<37 weeks) and term (≥37 weeks). Preterm preeclampsia can be effectively predicted at 11-13 weeks well before onset, and its incidence can be reduced by preventively using low-dose aspirin. However, late-onset and term preeclampsia are more prevalent than early forms and still lack effective predictive and preventive measures. This scoping review aims to systematically identify the evidence of predictive biomarkers reported in late-onset and term preeclampsia. This study was conducted based on the guidance of the Joanna Briggs Institute (JBI) methodology for scoping reviews. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRISMA-ScR) was used to guide the study. The following databases were searched for related studies: PubMed, Web of Science, Scopus, and ProQuest. Search terms contain "preeclampsia," "late-onset," "term," "biomarker," or "marker," and other synonyms combined as appropriate using the Boolean operators "AND" and "OR." The search was restricted to articles published in English from 2012 to August 2022. Publications were selected if study participants were pregnant women and biomarkers were detected in maternal blood or urine samples before late-onset or term preeclampsia diagnosis. The search retrieved 4,257 records, of which 125 studies were included in the final assessment. The results demonstrate that no single molecular biomarker presents sufficient clinical sensitivity and specificity for screening late-onset and term preeclampsia. Multivariable models combining maternal risk factors with biochemical and/or biophysical markers generate higher detection rates, but they need more effective biomarkers and validation data for clinical utility. This review proposes that further research into novel biomarkers for late-onset and term preeclampsia is warranted and important to find strategies to predict this complication. Other critical factors to help identify candidate markers should be considered, such as a consensus on defining preeclampsia subtypes, optimal testing time, and sample types.