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

Abstract

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.

Systematic review of the complement components as potential biomarkers of pre-eclampsia: pitfalls and opportunities

“…These preliminary findings emphasize the urgent need to investigate variations in the C components during pregnancy to identify potential predictive markers at early stages. As PE can have multiple causes, it is unlikely that a single timing strategy for biomarker testing can be used to predict all cases of PE ( 86 ). Despite requiring a massive effort from clinicians and researchers in terms of number of enrolled women, it is crucial that we embark on prospective longitudinal studies involving blood sample collection at various stages of pregnancy.…”

Use of cell-free signals as biomarkers for early and easy prediction of preeclampsia

“…Much research effort has targeted developing an easy and effective first-trimester PE screening tool. However, to date, no accurate single blood biomarker has been identified, particularly for prediction of late-onset PE ( 30 ). Although screening patients in the first trimester is optimal as it would allow implementation of timely prophylactic strategies for patients identified to be at risk of developing PE, we thought that it was also important to include a later timepoint (timepoint B) in our study.…”

Methodology for Biological Sample Collection, Processing, and Storage in the Newcastle 1000 Pregnancy Cohort: Protocol for a Longitudinal, Prospective Population-Based Study in Australia (Preprint)

“…Urine can be used for the detection and analysis of proteinuria, bacteria, infections, toxicology, renal function and nutrient markers [27][28][29]. Mid-stream urine samples will be requested at 14-, 20-, 28-, 36-weeks gestation and at 6-weeks postpartum from enrolled women.…”