Table 1.

Main biomarkers included in this review.

Biomarker	Characteristics	Role in pregnancy	Role in PE	Limitations in PE detection
PlGF	Vascular endothelial growth factor (VEGF) family member Expressed in the placental tissue [22] Mainly produced by trophoblasts [22]	Pivotal role in pregnancy angiogenesis [22] Serum levels increase at the end of the first trimester, peak at week 30, and decrease in the third trimester [23]	Used to rule out pre-eclampsia between 20 and 36 + 6 GW in women with symptoms but not meeting diagnostic criteria [24] Decreased serum levels between 28 and 30 GW [24] Lower levels in the first trimester [23]	Low sensitivity (32%) [23] High false-positive rate (5%) [23]
PAPP-A	Also known as pappalysin-1 High weight molecular glycoprotein (metalloproteinase) [25] Produced by placenta [25]	Levels rise as the gestation progresses [25] Routinely measured as part of the aneuploidy screening [26, 27, 28, 29] Lower levels associated with a higher chance of chromosomal abnormalities [26, 27, 28, 29]	Lower serum levels increase the risk of developing pre-eclampsia [30, 31, 32]	Low sensitivity [33] High false positive rate [33]
sFlt-1	Antiangiogenic tyrosine kinase protein [34] Binds PlGF and VEGF and blocks their pro-angiogenic effects [34] Mainly produced by placental tissue [35]	Higher serum levels in pregnancy (peak after 36 GW) [34]	Higher levels in PE for up to six months after delivery [34, 36, 37, 38, 39]	Used in combination with PlGF
β-hCG	Glycoproteic hormone [25] Produced by trophoblasts [25]	Promotes embryo implantation [25] Routinely used for early detection of pregnancy Levels peak at 8–9 GW, and decrease throughout pregnancy [40, 41] Used as part of the quad screening – levels higher in Trisomy 21, lower in Trisomy 13 and Trisomy 18 [42,43]	Higher levels in pre-eclamptic women as compared to healthy controls in the second trimester [44]	No definite link has been established [45, 46, 47, 48]
sFlt-1/PlGF			Diagnostic aid for pre-eclampsia detection [24] Higher levels in women who will develop pre-eclampsia [16, 49, 50]	Use regulated by NICE guidelines [24]
Leptin	Associated with adipogenesis and obesity [51, 52] The most abundant and studied adipokine in humans [51, 52]	Role has been investigated [53] Increased levels in pregnancy [54]	Higher levels in pre-eclampsia [54]	Studies on larger scale required
sEng	Transmembrane glycoprotein [55, 56] Actively involved in angiogenesis and inflammation [55, 56]	Role played in early pregnancy complications is an active area of research [57]	The higher the concentration, the more severe pre-eclampsia [58, 59, 60]	Studies on larger scale required
AFP	Albumin-like glycoprotein [61] Produced by the liver [61]	Levels measured as part of the triple and quadruple tests for chromosomal anomalies detection [62, 63]	No consistent correlation found [64, 65]	Studies on larger scale required
UA	Used to monitor a vast spectrum of systemic diseases	Concentrations decrease in first trimester and progressively increase up to delivery [66]	Evidence of hyperuricemia and pre-eclampsia [67]	Studies on larger scale required