Table 1.
Overview of studies on proteomic biomarkers for prediction of preterm birth (PTB).
| Study | Identified Biomarkers | Matrix | Size | When | Method |
|---|---|---|---|---|---|
| Targeted studies | |||||
| Massaro et al. (2009)24 | - IL-6 | - Amniotic fluid | - 8 PTB - 92 Term |
- 16–22 wks | - ELISA - p<0.05 |
| Manning et al. (2019)22 | - IL-1β - IL-8 - IL-6 |
- Cervical fluid | - 44 PTB - 90 Term - All with history of PTB or cervical surgery |
- 22–24 wks | - Multiplex platform - ELISA - PCR - Bonferroni corr. (p<0.01) |
| Goepfert et al. (2001)16 | - IL-6 | - Cervical fluid | - 125 PTB - 125 Term |
- 22–246/7 wks | - ELISA |
| Sorokin et al. (2010)28 | - IL-6 - CRP |
- Sera | - 47 PTB (<32 wks) - 423 Term |
- 24–32 wks | - ELISA - p<0.05 |
| Ghezzi et al. (2002)15 | - CRP | - Amniotic fluid | |||
| Wallenstein et al. (2016)30 | - sVEGFR-3 - sIL-2Rα - sTNFR1 |
- Sera | - 34 PTB - 34 Term - BMI>30 kg/m2 |
- 15–20 wks | - Random forest: classification and regression trees (CART) |
| Saade et al. (2016)27 | - IBP4/SHBG ratio | - Sera | - 248 Spontaneous PTB | - 19–21 wks | |
| Markenson et al. (2020)23 | - IBP4/SHBG ratio | ||||
| Khanam et al. (2022)20 | - IBP4/SHBG ratio | - 300 Women | |||
| Untargeted studies | |||||
| D’ Silva et al. (2018)13 | - 30, including 9 phosphoproteins, 11 glycoproteins - Pathways: blood coagulation, plasminogen activation, vitamin D metabolism, and angiogenesis |
- Sera | - 10 PTB - 10 Term |
- 11–13+6/7 wks | - 2DE and MS |
| Gunko et al. (2016)18 | - 25 including IL-6, VEGFA - Pathways: angiogenesis, proteolysis, transcription, inflammation processes, binding, and transportation of various ligands |
- Serum | - 10 PTB - 10 Term |
- 16–17 wks | - MS - p<0.05 |
| Pereira et al. (2010)25 | - Pathways: complement /coagulation cascade; inflammation/immune response; fetal-placental development; extracellular matrix proteins | - Serum (glycoproteome and peptidome) | - 48 Spontaneous PTB ≤33 wks - 62 PTB with GA≥34 wks |
- 20–336/7 wks | - p<0.05 |
| Jehan et al. (2020)8 |
- An inflammatory module | - Plasma | - 39 PTB - 42 term |
- Early pregnancy (median 13.6 wks) |
- targeted proteomics (1,002) AUC: 0.75 95% CI: 0.64, 0.85 |
| Tarca et al. (2021)29 | - PDE11A - ITGA2B - IL-6 - ANGPT1 - MMP7 - ITGA2B - Vascular wall pathways, nervous system development, developmental biology, focal adhesion, VEGFA/VEGFR-2 signaling, and membrane trafficking pathways |
- Plasma | - 62 Spontaneous PTB - 4 PPROM - 39 Term |
- 17–23 wks - 27–33 wks |
- targeted plasma proteomics (1,125) AUC: 0.76 95% CI: 0.72, 0.8 |
| Lynch et al. (2016)21 | - Complement factors B and H - Coagulation factors IX and IX ab - Pathways: complement cascade, the immune system, and the clotting cascade |
- Plasma | - 41 PTB - 88 Term |
- 10–15 wks |
- targeted proteomics (1,129) |
| Gudicha et al. (2022)17 | - SNAP25 GPI - PTPN11 - OLR1 - ENO1 - GAPDH - CHI3L1 - RETN - CSF3 - LCN2 - CXCL1 - CXCL8 - PGLYRP1 - LDHB - IL-6 - MMP8 - PRTN3 |
- Amniotic fluid | - 90 Women with a short cervix | - 1,310 proteins measured using aptamer-based multiplex platform (SOMAmer) | |
| Romero et al. (2008)26 | - 39 features identified | - Amniotic fluid | - 60 PTB - 59 Term |
- SELDI | |
| Hong et al. (2020)19 | - VEGFR-1 - Lipocalin-2 - Fc fragment of IgG binding protein |
- Amniotic fluid | - 139 | - 24–326/7 wks | - LC-MS - validation using ELISA |
IL, interleukin; ELISA, enzyme-linked immunosorbent assay; PCR, polymerase chain reaction; CRP, C-reactive protein; BMI, body mass index; 2DE, 2-dimensional gel electrophoresis; MS, mass spectrometry; AUC, area under the curve; CI, confidence interval; PPROM, preterm premature rupture of membranes; SELDI, surface enhanced laser desorption ionization; LC, liquid chromatography