Table 3:
Results from metabolomics Studies that did not Assess Biomarker Utility
| Authors | No. of metabolites | Results | Validated? | Conclusions |
|---|---|---|---|---|
| PE vs. control post diagnosis | ||||
| Jain S. et al (2004) | nr | plasmenyl phosphatidylethanolamine is decreased, but free fatty acids are increased in preeclamptic placenta | no | The majority of phospholipid species do not differ between preeclamptic and healthy placentas |
| Braekke K., et al. (2007) | 7 | Median concentrations of tCys, choline, and betaine were significantly greater in PE patients compared to controls | No | Cysteine, choline, and betaine were elevated in maternal and fetal plasma of preeclamptic compared to healthy pregnancies |
| . No significant difference was found between EO and LO patients, nor between severe and non-severe cases | ||||
| Turner E., et al. (2007) | Spectral signals between δ6 and 9.5 | Glucose levels are not an indicator of health of pregnancy. | No | Differing lipid levels in the plasma distinguish women with preeclampsia from those with normal pregnancies |
| The spectral region between 1.29 and 1.42 ppm contributed most to the separation, indicating decreased levels of lipids (mainly VLDL), lactate, fucose, and threonine in PE as compared to controls. | ||||
| The region between 0.87 and 0.96 ppm was also influential, containing lipids (including VLDL), cholesterol, isoleucine, and leucine. 2.22 to 2.26 ppm also emphasizes the importance of lipids. | ||||
| Turner E., et al. (2008) | Spectral signals between δ6 and 9.5 | Histidine, tyrosine, and phenylalanine were all found to be significantly higher in PE patients when compared to normotensive controls | No | 1H NMR in plasma is capable of differentiating between patients with and without preeclampsia |
| Kenny L.C., et al. (2008) | 45 metabolites | 8 discriminatory metabolites were validated; Alanine, 2-hydroxy-3-methyl-butanoic acid, 2-Ethyl-3-hydroxypropionic acid, 2-Oxoglutaric acid, Glutamic acid, Xylitol/ribitol, uric acid, Creatinine | Validation of Kenny et al. (2005) | Small-molecular-weight metabolites measured in serum can effectively detect preeclampsia |
| Pearson T. et al (2010) | 8 | Placentae of preeclamptic women contained significantly (P< 0.05) larger amounts of 5-HETE, 12-HETE and 15-HETE |
no | Increased production of 5-HETE, 12-HETE and 15-HETE metabolites in preeclamptic placentae indicates an important role for this family of eicosanoids in the cause of this disease. vasoconstrictive or proinflammatory actions |
| Dunn W.B., et al. (2012)(25) | 4825 metabolite features | Acyl glycerides, fatty acids and related metabolites, amino acid-related metabolites, Vitamin D-related metabolites, isoprenoids and steroids were decreased in PE cases; phospholipids were increased | No | Metabolomics of placenta has potential to aid in the understanding of pregnancy disorders |
| De Oliveira L., et al. (2012) | 1290 signals | 12 variables were identified with a PLS-DA VIP value > 2 and a p-value < 0.05. 1-acyl-lysophosphatidylcholine was found to be higher in PE patients than controls | No | Lipid fingerprinting in plasma is a useful method for future identification of metabolic biomarkers of early onset preeclampsia |
| Schott S., et al. (2012)(24) | 16 metabolites | 2-acyl-lysophosphatidylcholine and phosphatidylinositol were found to be lower in PE patients when compared to healthy controls. | No | Preeclampsia is associated with malfunction in membrane and/or phospholipid metabolism, although the causal relationship is unclear. |
| Total amount of phospholipids was not significantly different. | ||||
| HDL cholesterol levels were lower in PE cases, with a trend towards higher VLDL 2 and LDL 2. | ||||
| Baig S. et al. (2013) | ~200 | phosphatidylserine was significantly higher and ganglioside mannoside 3 (a sphingolipid) significantly lower in the STBM from PE patients compared to normal controls | No | Results suggest lipid metabolism is altered in the STBM of PE patients, which may relate to dysregulation of the immune response, coagulation, oxidative stress, and apoptosis. |
| Sohlberg S., et al. (2014) | 5 phosphorous metabolites (reported as 6 ratios) | EO-PE had a higher median PDE spectral intensity fraction than women with an early normal pregnancy. EO-PE also had a higher PDE/PME spectral intensity ratio. | No | Placental energy and membrane metabolism is affected in EO-PE compared to early normal pregnancies. They are not affected in LO-PE compared to late normal pregnancies |
| No significant difference in fractions of metabolites between LO-PE and controls | ||||
| Korkes et al. (2014) | 200 lipid signals | Plasma: PS (p=0.0001), PC (p=0.0001) and FLV (p=0.0001) were increased in PE cases relative to controls. Placenta:PS (p, 0.0001) and Macrolides/polyketides-PK04 (p,0.0001) were increased in PE cases relative to controls. | No | Lipid profiles differ in both the placenta and blood in healthy compared to preeclamptic pregnancies |
EO-PE-Early-onset preeclampsia; LO-PE-Late-onset preeclampsia; HDL-high density lipo-protein; VLDL-very low density lipo-protein; LDL-low density lipo-protein; PDE- phosphodiesters; PME- phosphomonoesters; PLS-DA – partial least squares discriminant analysis; VIP – Variable Importance in the projection