Table 1.
Summary of Extracellular DNA Biomarkers Evaluated to Differentiate Between Normal Pregnancies and Those with Placental Insufficiency
| Placental insufficiency | Marker | Reference |
|---|---|---|
| SRY gene | ||
| Onset | ↑ PE | Lo et al. (1999), Zhong et al. (2001), Lau et al. (2002), Farina et al. (2004b), Engel et al. (2007) |
| ↑ PE±IUGR | Smid et al. (2001), Hromadnikova et al. (2009), Hromadnikova et al. (2010b) | |
| Positive correlation between DNA levels and the severity of PE | Zhong et al. (2001), Engel et al. (2007) | |
| ↑ IUGR | Smid et al. (2001) | |
| ≅ IUGR | Hromadnikova et al. (2010b) | |
| Before onset | ↑ PE (17–18 weeks) | Leung et al. (2001) |
| ↑ PE (21 weeks) | Zhong et al. (2007) | |
| ↑ IUGR (20–35 weeks) association with abnormal uterine artery Doppler waveforms |
Caramelli et al. (2003) | |
| ↑ PE and/or IUGR, but strongly individual (12–36 weeks) | Hromadnikova et al. (2010b) | |
| ≅ IUGR (21 weeks) | Zhong et al. (2007) | |
| DYS-14 sequence | ||
| Onset | ↑ PE | Alberry et al. (2009), Sekizawa et al. (2003) |
| ↑ PE±IUGR | Hromadnikova et al. (2009) | |
| Positive correlation between DNA levels and the severity of PE | Alberry et al. (2009) | |
| ↑ IUGR | Alberry et al., 2009 | |
| ≅ IUGR | Sekizawa et al. (2003) | |
| Interindividual copy number variations influence quantification of extracellular fetal DNA | Hromadnikova et al. (2009) | |
| Before onset | ↑ early PE (11–13 weeks) association between DNA levels and uterine artery pulsatility index |
Sifakis et al. (2009) |
| ↑ PE and/or IUGR before 35 weeks ≅ PE and/or IUGR after 35 weeks (11–14 weeks) |
Illanes et al. (2009) | |
| ↑ PE (18–21 weeks) | Farina et al. (2004c), Zhong et al. (2007) | |
| ≅ IUGR (21 weeks) | Zhong et al. (2007) | |
| DYS-1 sequence | ||
| Before onset | ↑ two-stage elevation in PE (17–28 weeks) and 3 weeks before onset of clinical symptoms |
Levine et al. (2004) |
| Hypermethylated RASSF1A sequence | ||
| Onset | ↑ PE | Tsui et al. (2007), Zhao et al. (2010) |
| ↑ PE±IUGR | Hromadnikova et al. (2010b) | |
| Positive correlation between DNA levels and the severity of PE | Zhao et al. (2010) | |
| ≅ onset IUGR | Hromadnikova et al. (2010b) | |
| Before onset | ↑ PE and/or IUGR is strongly individual (12–36 weeks) | Hromadnikova et al. (2010b) |
| GLO gene | ||
| Onset | ↑ PE | Sekizawa et al. (2003) |
| ↑ PE±IUGR | Hromadnikova et al. (2009), Hromadnikova et al. (2010b) | |
| ↑ IUGR | Hromadnikova et al. (2010b) | |
| Before onset | ↑ PE and/or IUGR is strongly individual (12–36 weeks) | Hromadnikova et al. (2010b) |
| GAPDH gene | ||
| Onset | ↑ PE | Zhong et al. (2001) |
| Positive correlation between DNA levels and the severity of PE | Zhong et al. (2001) | |
| Before onset | ≅ PE and/or IUGR (21 weeks) | Zhong et al. (2007) |
↑ PE, extracellular DNA levels are increased in patients with PE; ≅ IUGR, extracellular DNA levels do not differ between controls and patients with IUGR; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; SRY, sex-determining region Y; IUGR, intrauterine growth restriction; PE, pre-eclampsia.