Clinical Presentation of Preeclampsia and the Diagnostic Value of Proteins and Their Methylation Products as Biomarkers in Pregnant Women with Preeclampsia and Their Newborns

Table 2

List of proposed serum biomarkers for the detection and diagnosis of PE.

Proposed biomarker	Biological role	Serum level in PE compared to normotensive pregnancy	Type of study	Positive predictive value	References
Soluble fms-like tyrosine kinase 1 (sFlt-1)	Anti-angiogenic factor	Higher	Case-control	No	[24, 46–51]
			Nested case-control	No	[52, 53]
			Cross-sectional case-control	No	[54–56]
			Longitudinal case-control	No	[57, 58]
			Prospective cohort	No	[59, 60]
				Yes	[61]
			Prospective nested case-control	No	[62]
Placental growth factor (PlGF)	Angiogenic factor	Lower	Case-control	No	[24, 46, 48, 50, 51]
				Yes	[63–65]
			Nested case-control	No	[52, 53, 66]
			Cross-sectional case-control	No	[54–56]
			Longitudinal case-control	No	[57, 58, 67]
				Yes	[68]
			Prospective cohort	No	[59, 60]
				Yes	[61]
			Prospective nested case-control	No	[62]
			Prospective longitudinal case-control	No	[69]
			Longitudinal cohort	No	[70]
			Longitudinal cross-sectional	No	[71, 72]
Asymmetric Dimethyl-Arginine (ADMA)	Biochemical degradation product	Higher	Case-control	No	[73–77]
			Longitudinal case-control	No	[78–82]
			Cross-sectional case-control	No	[83, 84]
Soluble Endoglin (sEng)	Modulator of transforming growth factor (TGF)-β signalling	Higher	Longitudinal case-control	No	[58]
			Cross-sectional case-control	No	[85, 86]
			Nested case-control	No	[87, 88]
			Retrospective	No	[89]
			Prospective	No	[90]
			Case-control	No	[91]
Placental Protein 13 (PP-13)	Lysophospholipase activity	Higher	Longitudinal case-control	No	[92, 93]
			Nested case-control	No	[94–98]
			Case-control	No	[99]
P-Selectin	Calcium-dependent receptor	Higher	Cross-sectional case-control	No	[100–105]
				Yes	[106]
			Longitudinal case-control	No	[107]
				Yes	[108]
Adrenomedullin	Vasodilator	Higher	Cross-sectional case-control	No	[109]
A Disintegrin and Metalloprotease 12 (ADAM12)	Cell-cell and cell-matrix interaction protease	Lower	Retrospective case-control	No	[110]
			Cross-sectional case-control	No	[111, 112]
Pentraxin 3 (PTX3)	Angiogenesis and inflammation factor	Higher	Cross-sectional case-control	No	[113, 114]
Pregnancy-Associated Plasma Protein A (PAPP-A)	Metalloproteinase that cleaves insulin-like growth factor binding proteins (IGFBPs)	Lower	Case-control	Yes	[64]
			Nested case-control	No	[98]
			Cross-sectional case-control	No	[115–118]
			Retrospective cohort	No	[119–122]
			Prospective cohort	No	[123]
Nicotinamide Phosphoribosyltransferase; Visfatin	Enzyme involved in nicotinamide metabolism	Both	Cross-sectional case-control	No	[124]
Cell free DNA	N.A	Higher	Cross-sectional case-control	No	[125–127]
Cell-free foetal DNA	N.A.	Higher	Cross-sectional case-control	No	[127–129]
			Nested case-control	No	[130, 131]
			Prospective	No	[132, 133]