Preeclampsia (PE) affects 2-8% of pregnancies worldwide, thus representing an important cause of maternal and neonatal morbidity, up to death. Many studies have been designed to identify putative biomarkers for accurate and timely diagnosing PE, but only some of them were focused on specific and sensitive biomarkers for early prediction of this life-threatening condition. In particular, some prospective studies aimed to investigate the predictive role of circulating biomarkers before 20 weeks of gestation in the general pregnant population yielded conflicting results. This article is hence centered on results obtained in studies investigating the predictive performances of angiogenic, anti-angiogenic, inflammatory, endocrine and epigenetic biomarkers. The available evidence suggests that angiogenic and anti-angiogenic molecules, in particular the sFlt1:PlGF ratio, may be considered the biomarkers with the best diagnostic performance in the second trimester. However, doubts remain about their use in clinical settings before the 20(th) gestational week. An even lower evidence is available for other biomarkers, due to the fact that some positive results have not been confirmed in ensuing investigations, whereas unresolved analytical issues still contribute to make their clinical reliability rather questionable. Differential expression of microRNAs seems also a promising evidence for early prediction of PE, but additional research and well-designed prospective studies are needed to identify and validate routine predictive tests.
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