Table 3.
The Potential of Metabolic Markers for the Prediction of PE
| Author | Comparison Groups | Bio-Specimen | Sensitivity | Specificity | AUC | Potential Biomarkers | |
|---|---|---|---|---|---|---|---|
| Sovio12 | Preterm PE | 12w | - | - | 0.887 | PGAPE, PAPPA, PlGF, 4-hydroxyglutamate | |
| Preterm PE | 20w | - | - | 0.911 | PGAPE, sFlt1/PlGF, 4-hydroxyglutamate | ||
| Preterm PE | 28w | - | - | 0.926 | PGAPE, sFlt1/PlGF, 4-hydroxyglutamate, C-glycosyltryptophan | ||
| Lee13 | PE | Mid-trimester cohort | 0.751 | 0.830 | 0.868 | SM C28:1, SM C30:1, LysoPC C19:0, LysoPE C20:0, propane-1,3-diol | |
| PE | At-delivery cohort | 0.693 | 0.846 | 0.858 | SM C28:1, SM C30:1, LysoPC C19:0, LysoPE C20:0, propane-1,3-diol | ||
| 0.786 | 0.714 | 0.844 | SM C30:1 | ||||
| 0.838 | 0.799 | 0.904 | SM C30:1, oxidized PE C38:3 | ||||
| 0.923 | 0.857 | 0.972 | SM C30:1, oxidized PE C38:3, isomaltose | ||||
| Kenny14 | Preterm PE | 15±1w | 0.650 | 0.830 | 0.780 | PlGF, dilinoleoyl-glycerol, 1-heptadecanoyl-2-hydroxy-sn-glycero-3 phosphocholine | |
| Liu17 | PE | 34w | - | - | 0.895 | 14,15-DiHETE | |
| - | - | 0.830 | 16-HDoHE | ||||
| - | - | 0.820 | LTB4 | ||||
| - | - | 0.795 | 8,9-EEQ | ||||
| Powell22 | PE | 26–41w | 0.870 0.600 |
0.917 0.955 |
0.938(discovery) 0.936(validation) |
3-Methylhistidine, creatinine, acetyl groups, acetate | |
| Zhou24 | Severe PE | Immediately after the cesarean section | 0.870 | 0.830 | 0.930 | Arachidonate | |
| 0.930 | 0.830 | 0.930 | Docosapentaenoate | ||||
| 0.860 | 0.890 | 0.920 | γ-Linoleate | ||||
| 0.930 | 0.890 | 0.930 | Myristate | ||||
| 0.860 | 0.830 | 0.920 | Dihomo-γ-linoleate | ||||
| Chen26 | PE | 21.7–27.9w(PE) 18.6–27.4w(control) |
- | - | 0.935 | PC(14:0/00) | |
| - | - | 0.928 | Proline betaine | ||||
| - | - | 0.923 | Proline | ||||
| Bahado-Singh27 | LO-PE | Within 3 d of assessment | 0.304 | 0.804 | 0.629(validation) | Carnitine, pyruvate, acetone | |
| 0.391 | 0.804 | 0.722(validation) | UtPI, pyruvate, carnitine, glycerol | ||||
| 0.348 | 0.826 | 0.734(validation) | Maternal weight, UtPI, pyruvate, carnitine | ||||
| Bahado-Singh28 | Term PE | First trimester | 0.727 | 0.574 | 0.701 | Putrescine, urea, carnitine | |
| Term PE | Third trimester | 0.742 | 0.723 | 0.761 | Methylhistidine, serotonin, citrate, hexose, propylene glycol | ||
| Term PE | Integrated first and third trimester | 0.816 | 0.710 | 0.817 | Urea (1st), SM C18:1 (1st), citrate (3rd), hexose (3rd) | ||
| Koster29 | EO-PE | 8+0–13+6w | - | - | 0.878(training) 0.784(validation) |
MC, MAP, PAPPA, PlGF, taurine, stearoylcarnitine | |
| LO-PE | 8+0–13+6w | - | - | 0.833(training) 0.700(validation) |
MC, MAP, PAPPA, PlGF, stearoylcarnitine | ||
| Bahado-Singh30 | EO-PE | Within 3 d of assessment | 0.825 0.750 |
0.823 0.744 |
0.896(discovery) 0.835(validation) |
2-Hydroxybutyrate,3-hydroxyisovalerate, acetone, citrate, glycerol | |
| 0.908 0.900 |
0.908 0.884 |
0.956(discovery) 0.916(validation) |
3-Hydroxyisovalerate, arginine, glycerol, UtPI | ||||
| Austdal32 | PE | 11+0–13+6w | 0.192 | - | 0.694 | Hippurate/creatinine | |
| 0.423 | - | 0.778 | Hippurate/creatinine, MAP, maternal age | ||||
| 0.538 | - | 0.807 | Hippurate/creatinine, MAP, UtPI, maternal age | ||||
| Bahado-Singh39 | LO-PE | 11+0–13+6w | 0.600 | 0.966 | 0.885(primary dataset) | Methylhistidine, glycerol, maternal weight, maternal race, acetoacetate | |
| 0.767 | 1.000 | 0.960(primary dataset) | Valine, maternal weight, maternal race, pyruvate, 3-hydroxybutyrate, 1-methylhistidine, glycerol, trimethylamine, maternal medical disorder | ||||
| 0.400 | 0.941 | 0.790(expanded dataset) | Glycerol | ||||
| 0.400 | 0.950 | 0.796(expanded dataset) | Glycerol, maternal weight | ||||
| 0.567 | 0.950 | 0.783(expanded dataset) | Glycerol, 1-methylhistidine | ||||
| Bahado-Singh40 | EO-PE | 11–13w | 0.759 | 0.951 | 0.904 | Citrate, glycerol, hydroxyisovalerate, methionine | |
| 0.826 | 0.984 | 0.980 | Acetate, glycerol, hydroxyisovalerate, UtPI, fetal CRL | ||||
| 0.500 | 0.950 | 0.840 | Glutamine, pyruvate, propylene glycol, trimethylamine, hydroxy butyrate, maternal weight, maternal medical disorders | ||||
| 0.600 | 0.970 | 0.940 | Pyruvate, propylene glycol, trimethylamine, 3-hydroxisovalerate, UtPI | ||||
| Odibo41 | PE | 11–14w | - | - | 0.824 | Hydroxyhexanoylcarnitine, phenylalanine, glutamate, alanine | |
| EO-PE | - | - | 0.846 | Hydroxyhexanoylcarnitine, phenylalanine, glutamate, alanine | |||
| PE | - | - | 0.818 | Phenylalanine, glutamate, alanine | |||
| Kenny42 | PE | 15±1w | - | - | 0.940(discover) 0.920(validation) |
5-Hydroxytryptophan, monosaccharide(s), decanoylcarnitine, methylglutaric acid and/or adipic acid, oleic acid, docosahexaenoic acid and/or docosatriynoic acid, γ-butyrolactone and/or oxolan-3-one, 2-oxovaleric acid and/or oxo-methylbutanoic acid, acetoacetic acid, hexadecenoyl-eicosatetraenoyl-sn-glycerol, di-(octadecadienoyl)-sn-glycerol, sphingosine 1-phosphate, sphinganine 1-phosphate, vitamin D3 derivatives | |
| McBride47 | PE | 22–28w | - | - | 0.620(training and testing) 0.620(validation) 0.710(training and testing) 0.630(validation) 0.680(training and testing) 0.660(validation) |
Risk factor (BMI, age, parity, smoking) Risk factor (BMI, age, parity, smoking) Metabolite (154 metabolites) Metabolite (154 metabolites) Combined (BMI, parity, 26 metabolites) Combined (BMI, parity, 26 metabolites) |
|
Abbreviations: AUC, area under the curve; PGAPE, the predicted gestational age of pre-eclampsia; PAPPA, pregnancy-associated plasma protein A; PLGF, placenta growth factor; sFlt1, soluble fms-like tyrosine kinase 1; UtPI, uterine artery pulsatility index; MC, maternal characteristics; MAP, mean arterial pressure; fetal CRL, fetal crown-rump length; BMI, body mass index.