Gestation Dependant Changes in Angiogenic Factors and Their Associations with Fetal Growth Measures in Normotensive Pregnancy

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.

A longitudinal study of circulating angiogenic and antiangiogenic factors and AT1-AA levels in preeclampsia

“…Furthermore, it is reported that during the second trimester, the maternal PlGF levels are high and the maternal sFlt-1 levels are low, creating a proangiogenic state. 19,25 In women with PE, sFlt-1 appears to increase earlier in gestation and reach a higher level than it does in controls, possibly leading to altered placental growth and function.…”

“…Our study design has been previously reported by us in normotensive women. 25 Among the 46 normotensive women and 35 women with PE who were enrolled, the first time point blood sample was obtained from 42 normotensive women and 35 women with PE, the second time point blood sample was obtained from 43 normotensive women and 25 women with PE and the delivery sample was obtained from 45 normotensive women and 24 women with PE. An umbilical cord blood sample was obtained from 46 normotensive women and 34 women with PE.…”

“…25 VEGF, PlGF, sFlt-1, sKDR and AT1-AA levels from maternal and cord plasma Plasma VEGF, PlGF sFlt-1 and sKDR levels were measured in both maternal samples and cord samples using commercial enzyme-linked immunosorbent assay (ELISA) kits (R&D Systems, Minneapolis, MN, USA), and the procedures have previously been described by us. 15 For the sFlt-1 and sKDR assay, plasma samples were diluted 1:5 (vol/vol) in calibrator diluent before following the remaining assay procedure of the manufacturer.…”

“…Our results indicate that maternal VEGF levels in early gestation (16-20 weeks) play an important role in predicting birth weight in healthy term pregnancies. 25 The current study was undertaken to examine changes in the maternal plasma levels of angiogenic (VEGF and PlGF) and antiangiogenic (sFlt-1 and sKDR) factors and AT1-AAs throughout gestation, from early pregnancy until delivery, as well as their association with blood pressure, cord levels at delivery and birth weight in women with PE. The study also examined whether the sFlt-1/PlGF ratio in early pregnancy could be useful in determining the risk for developing PE.…”

Fetal Growth and Placental Growth Factor Umbilical Cord Blood Levels

“…Unfortunately no maternal PlGF levels at the end of pregnancy were available within our cohort. During pregnancy, PlGF reaches its peak around 31 weeks of gestation, after which it declines [7,22] . Around the time of delivery, levels of maternal PlGF are comparable with levels around 19 weeks of gestation.…”