Abstract
BackgroundEarlier studies indicate that altered angiogenesis at birth is associated with poor birth outcome in women with preeclampsia. Now, we hypothesize that the progressive gestation dependant changes in markers of angiogenesis will be more useful to predict birth weight early even in a normotensive pregnancy. This study for the first time examines the association of gestation dependant changes in the levels of maternal angiogenic factors in addition to their levels in cord with birth weight.MethodNinety two pregnant women were followed at three different time points: 16–20 weeks, 26–30 weeks and at delivery during pregnancy. Plasma levels of angiogenic and anti angiogenic factors were determined by commercial enzyme-linked immunosorbent assay (ELISA) kits.ResultsMaternal plasma VEGF levels increased (p<0.01) till the second time point and decreased (p<0.05) up to delivery while plasma sFlt-1 levels increased (p<0.01) at delivery. PlGF levels peaked (p<0.01) at second time point and decreased (p<0.01) at delivery. Cord plasma VEGF levels were higher (p<0.01) and sFlt-1 levels were lower (p<0.01) as compared to maternal values at all time points. Maternal plasma VEGF levels at first time point and PlGF levels at delivery were positively (p<0.05 and p<0.01 respectively), while sFlt-1/PlGF ratio at delivery was negatively associated (p<0.05) with birth weight.ConclusionLevels of pro- and anti-angiogenic factors may be differentially regulated across gestation. Maternal VEGF levels at early gestation (16–20 weeks) may be predictive of birth weight in healthy term pregnancies.
Highlights
Vascular growth and remodelling are considered to be central for placental and fetal growth [1]
Biological actions of vascular endothelial growth factor (VEGF) and Placental growth factor (PlGF) are primarily mediated through binding to their membrane associated tyrosine-kinase receptors, VEGFR-1 or VEGFR-2 [6]. sVEGFR-1 or soluble fms like tyrosine kinase-1 receptor is a soluble receptor and is considered to be an anti-angiogenic factor as it adheres to PlGF and VEGF leading to endothelial dysfunction [2,7]
It has been suggested that the soluble fms like tyrosine kinase-1 receptor (sFlt-1)/PlGF ratio could be a biomarker in determining women who are at risk of developing preeclampsia [9]
Summary
Vascular growth and remodelling are considered to be central for placental and fetal growth [1]. Angiogenesis is tightly regulated by a number of pro- and anti-angiogenic factors, where the vascular endothelial growth factor (VEGF) family plays a central role. SVEGFR-1 or soluble fms like tyrosine kinase-1 receptor (sFlt-1) is a soluble receptor and is considered to be an anti-angiogenic factor as it adheres to PlGF and VEGF leading to endothelial dysfunction [2,7]. Our earlier cross sectional studies in women with preeclampsia at the end of pregnancy indicate altered angiogenesis which was associated with poor birth outcome [8]. These effects are likely to be confounded by secondary effects of the disease. This study for the first time examines the association of gestation dependant changes in the levels of maternal angiogenic factors in addition to their levels in cord with birth weight
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