Table 1.
Summary of current clinical studies of potential biomarkers for PE based on major hypotheses.
| Biomarkers | Subjects | Sample | Limitation | Refs. |
|---|---|---|---|---|
| 1. The placental or trophoblast ischemia and hypoxia hypothesis | ||||
| PAPP-A | 42 PE; 410 controls |
Serum (11–14 weeks of gestation) | The sample size was small, especially cases with PE. | [9] |
| AT1-AA | 30 PE； 30 gestational age-matched controls; |
Serum (three stages: <27; 28–33; >34 weeks of gestation; prospective study) | The sample size was small; Low sensitivity. | [12] |
| PP-13 | 47 PE; 290 controls |
Serum (9–12 weeks of gestation) | Inconsistent test reagents. | [15] |
| 42 PE; 410 controls |
Serum (11–14 weeks of gestation) | [9] | ||
| HGF | 52 PE; 104 controls |
Plasma (15–20 weeks of gestation) | The study population was single; The detection time was relatively late. | [19] |
| HIF-1 | 23 early-onset PE; 23 late-onset PE; 23 controls |
Serum (≥20 weeks of gestation; cross-sectional study) | A few cases were classified as early-onset PE or late-onset PE for the research. | [21] |
| miR-210 | 20 PE; 56 controls |
Serum (15–20 weeks of gestation) | The sample size was small; Low specificity. | [24] |
| 2. The oxidative stress hypothesis | ||||
| ROS | 80 PE; 80 controls |
Plasma (29–41 weeks of gestation) | Low specificity. | [27] |
| HbF | 86 PE; 347 controls |
Serum (mean 13.7 weeks of gestation) | The cohort had a higher level of risk factors for PE than a normal population. | [29] |
| A1M | 86 PE; 347 controls |
Serum (mean 13.7 weeks of gestation) | The sample size was small; Low specificity. | [29] |
| 41 PE; 50 controls |
Serum (30–39 weeks of gestation) | [31] | ||
| Hcy | 103 mild PE; 44 severe PE; 4418 controls |
Serum (11–13 weeks of gestation) | Samples were not collected repeatedly. | [33] |
| 3. The immune dysregulation hypothesis | ||||
| NLR | 49 mild PE; 15 severe PE; 376 controls |
Venous blood(16–18 weeks of gestation) | The sample size of the patients was small; Low sensitivity. | [38] |
| TH | 9 PE; 77 controls |
Serum (5–16 weeks of gestation) | The cohort had a higher level of risk factors for PE than a normal population; The number of patients with PE is limited. | [43] |
| CRP | 26 mild PE; 33 severe PE; 50 controls |
Serum (34–38 weeks of gestation) | The study was cross-sectional; The sample size of the patients was small. | [45] |
| NGAL | 128 PE; 183 controls |
Serum (10–14 weeks of gestation) | A relatively small number of participants; Low specificity. | [47] |
| 4. The vascular endothelial injury hypothesis | ||||
| TG | 139 mild PE; 143 severe PE; 37 controls |
Plasma (27–30 weeks of gestation) | This parameter is variable and affected by multiple influences, duplicate and continuous monitoring is required; Low specificity. | [50] |
| 53 early-onset PE; 18 late-onset PE; 2086 controls |
Plasma (at 18 weeks of gestation) | [51] | ||
| PlGF | 60 mild PE; 60 severe PE; 30 controls |
Serum (26–28 weeks of gestation) | High specificity and sensitivity when combined with other parameters. | [53] |
| 62 PE; 1560 controls |
Plasma (6–15 and 20–25 weeks of gestation) | [54] | ||
| VEGF | 23 non-severe PE; 19 severe PE; 42 controls |
Placenta (immediately after the delivery) | A study with a case-control model in a different population is needed. | [56] |
| 40 late-onset PE; 40 controls |
Serum (32–38 weeks of gestation) | [57] | ||
| sFlt-1 | 15 early-onset PE; 19 late-onset PE; 144 controls |
Plasma (19–25, 27–31 and 34–38 weeks of gestation) | A few cases were classified as early-onset PE or late-onset PE for research; High specificity and sensitivity when combined with other parameters. | [59] |
| 62 PE; 1560 controls |
Plasma (6–15 and 20–25 weeks of gestation) | [54] | ||
| sEng | 62 PE; 1560 controls |
Plasma (6–15 and 20–25 weeks of gestation) | The cohort had a higher level of risk factors for PE than a normal population; The detection time is relatively late. | [54] |
| 54 PE; 28 controls |
Serum (after clinical manifestations) | [61] | ||
| CC | 52 PE; 52 controls |
Serum (24–36 weeks of gestation) | The study was cross-sectional; Low specificity. | [65] |
Controls: the normotensive pregnant women who didn’t develop any pregnancy complications.
Abbreviations: PAPP-A, Pregnancy-associated plasma protein-A; AT1-AA, Angiotensin II type 1 receptor autoantibody; PP-13, Placental protein-13; HGF, Hepatocyte growth factor; HIF-1, Hypoxia-inducible factor-1; miR-210, microRNA 210; ROS, Reactive oxygen species; HbF, Fetal hemoglobin; A1M, α1 microglobulin; Hcy, Homocysteine; TH, Helper T cell; CRP, C-reactive protein; NGAL, Neutrophil gelatinase-associated lipocalin; NLR, Neutrophil/lymphocyte ratio; TG, Triglyceride; PlGF, Placental growth factor; VEGF, vascular endothelial growth factor; sFlt-1, soluble tyrosine kinase-like receptor-1; sEng, soluble endothelin; CC, Cystatin C.