Circulating EGFL7 distinguishes between IUGR and PE: an observational case-control study

Abstract

Isolated intrauterine growth restriction (IUGR) and preeclampsia (PE) share common placental pathogenesis. Differently from IUGR, PE is a systemic disorder which may also affect liver and brain. Early diagnosis of these conditions may optimize maternal and fetal management. Aim of this study was to assess whether Epidermal Growth Factor-Like domain 7 (EGFL7) dosage in maternal blood discriminates between isolated IUGR and PE. A total of 116 women were enrolled in this case-control study: 12 non-pregnant women, 34 healthy pregnant women, 34 women presenting with isolated IUGR and 36 presenting with PE. Levels of circulating EGFL7 and other known pro- and anti-angiogenic factors were measured by ELISA at different gestational ages (GA). Between 22-25 weeks of gestation, EGFL7 levels in early-onset PE (e-PE) plasma samples were significantly higher than those measured in controls or isolated IUGR samples (69.86 ± 6.17 vs. 19.8 ± 2.5 or 18.8 ± 2.8 µg/ml, respectively). Between 26-34 weeks, EGFL7 levels remained significantly higher in e-PE compared to IUGR. At term, circulating and placental EGFL7 levels were comparable between IUGR and late-onset PE (l-PE). In contrast, circulating levels of PlGF were decreased in both IUGR- and PE- complicated pregnancies, while levels of both sFLT-1 and sENDOGLIN were increased in both conditions. In conclusion, EGFL7 significantly discriminates between isolated IUGR and PE.

Figure 1

EGFL7 levels in non-pregnant women, healthy pregnant women, and pregnant women affected by IUGR, Early PE and Late PE. (A) Mean (± SE) levels of Epidermal Growth Factor-like Domain 7 (EGFL7) in plasma of non-pregnant women (NP), healthy pregnant women (Controls), IUGR-, Early PE- (e-PE) and Late PE- (l-PE) affected pregnant women throughout pregnancy as measured by ELISA. Data were compared using the two-sample t-test between two samples (p < 0.001 for e-PE vs. CTRL and IUGR at GA 22–25; p = 0.05 for e-PE vs. CTRL and IUGR at GA 26–30; p = 0.045 for e-PE vs. IUGR at GA 31–34; p = 0.01 for l-PE vs. CTRL) or ANOVA test among the three studied groups (p < 0.001 at GA 22–25 and p = 0.036 at GA 35–40). Statistically significant difference within gestational interval is reported. SigmaPlot 12.0 and GraphPad Prism 7 were used for statistical analysis. (B) Real-time PCR analysis for EGFL7 gene expression levels in placental samples obtained from Controls, IUGR- and l-PE- affected pregnant women at GA 35–40. Data were represented as mean (± SE). ANOVA test with post-hoc Bonferroni correction was used for statistical analysis (SigmaPlot 12.0). Differences were considered significant at p < 0.05.

Figure 2

PlGF, sFLT-1 and sENDOGLIN levels in non-pregnant, healthy pregnant women, IUGR-, Early PE- and Late PE- affected pregnant women along gestation. Mean (± SE) levels of Placental Growth Factor (PlGF, (A), soluble fms-like tyrosine kinase 1 (sFLT-1, (B) and soluble Endoglin (sENDOGLIN, (C) in plasma of non-pregnant women (NP), healthy pregnant women (Controls), IUGR-, Early PE- (e-PE) and Late PE- (l-PE) affected pregnant women throughout pregnancy as measured by ELISA. Statistically significant difference within gestational interval is reported. Data were compared using the two-sample t-test between two samples or ANOVA test among more than two groups. Statistically significant difference within gestational interval is reported. SigmaPlot 12.0 and GraphPad Prism 7 were used for statistical analysis.