Angiogenic growth factor levels in maternal and fetal blood: correlation with Doppler ultrasound parameters in pregnancies complicated by pre‐eclampsia and intrauterine growth restriction

Schlembach, Dietmar; Wallner, W.; Sengenberger, R.; Stiegler, E; Mörtl, M; Beckmann, MW; Lang, Uwe

doi:10.1002/uog.3930

Cited by 94 publications

(81 citation statements)

References 34 publications

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“…50 In this study, cord plasma PlGF levels were below the detection limit in both groups, and similar findings were previously reported. 51,15 In our study, sFlt-1 levels in cord plasma were increased, although they were not significant in preeclampsia, consistent with earlier reports. 51 Some studies have also shown that infants with maternal preeclampsia had higher cord blood sFlt-1 but lower PlGF and VEGF levels.…”

Section: Discussionsupporting

confidence: 92%

“…Several studies carried out in Western countries have consistently reported increased levels of plasma sFlt-1 8,15,[34][35][36][37][38][39][40][41] in mothers with preeclampsia compared with normotensive women. Our results suggest that Indian women with preeclampsia also have a similar increase in plasma sFlt-1 levels.…”

Section: Discussionmentioning

confidence: 98%

“…Most of the published studies have examined the levels of all the angiogenic factors in a small number of mother and cord samples. 9,15 Furthermore, their associations with birth outcome are very rarely examined. 16 Very little is known about the mechanisms by which factors such as sFlt-1 may contribute to the preeclamptic syndrome.…”

Section: Introductionmentioning

confidence: 99%

“…17 It is suggested that sFlt-1 binds to both VEGF and PlGF, 18,19 reducing their free levels in the blood by working as a soluble antagonist of both factors. 20 It is believed that hypoxia in preeclampsia leads to increased production of sFlt-1 in placental trophoblasts 15,21 and is suggested to be the major source of circulating sFlt-1. 22 Others believe that hypoxia may not be the only or main stimulus to release sFlt-1 and emphasize the role of inflammatory mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Circulating angiogenic factors and their association with birth outcomes in preeclampsia

et al. 2010

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This study was designed to test the hypothesis that altered angiogenic factors together with increased oxidative stress and reduced docosahexaenoic acid (DHA) levels may be associated with altered birth outcome parameters. To test this hypothesis, levels of plasma vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), the oxidative stress marker malondialdehyde (MDA) and fatty acids were estimated in women with preeclampsia and their cord samples and compared with those in normotensive women. The association of these parameters with birth outcome was also examined. Our results show that in preeclamptic women, maternal plasma VEGF and PlGF levels were lower, whereas sFlt-1 levels were higher (Po0.05 for all) than in normotensive women. In contrast, cord plasma VEGF levels were higher (Po0.05) in preeclamptic women, whereas there was no difference in sFlt-1 levels. Plasma DHA levels in both the mother and cord were lower (Po0.05) in the preeclamptic group compared with normotensive women. Maternal plasma sFlt-1 levels were positively (n¼23, r¼0.415, P¼0.039) associated with MDA concentrations in preeclamptic women. Maternal plasma sFlt-1 levels showed a strong negative association with baby weight (n¼37, r¼À0.547, P¼0.001), head circumference (n¼37, r¼À0.472, P¼0.005) and baby chest circumference (n¼37, r¼À0.375, P¼0.032) in the preeclamptic group. Cord plasma sFlt-1 concentrations were negatively associated with cord plasma DHA concentrations (n¼28, r¼À0.552, P¼0.004). This study suggests that dysregulation of angiogenic factors may be associated with maternal oxidative stress. Increased oxidative stress may reduce cord DHA levels and increase sFlt-1 levels, leading to poor birth outcomes in preeclampsia.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Circulating angiogenic factors and their association with birth outcomes in preeclampsia

et al. 2010

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“…One of the main features in the placenta from a preeclamptic pregnancy is failure of spiral artery remodeling, a phenomenon linked not only with reduced maternal blood flow toward the placenta [4] but also with high velocity and pressure of maternal inflow that may impair the placental villous structure [5]. Both a reduction in placental blood flow and impaired placental structure have been associated with neonatal complications following preeclampsia, such as growth retardation [4][5][6][7]. Specifically, Doppler studies reveal that impaired feto-placental blood flow is mainly evident in women with early-onset preeclampsia (EOPE) [8] rather than late-onset preeclampsia (LOPE) [9].…”

Section: Introductionmentioning

confidence: 99%

Impaired A2A adenosine receptor/nitric oxide/VEGF signaling pathway in fetal endothelium during late- and early-onset preeclampsia

Escudero

Bertoglia

Hernadez

et al. 2012

Purinergic Signalling

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To investigate whether fetal endothelial cell proliferation and migration are modulated by the A 2A adenosine receptor (A 2A AR), nitric oxide (NO) and the vascular endothelial growth factor (VEGF) signaling pathway, we isolated human umbilical vein endothelial cells from normal pregnancy (n023), preterm delivery (n04), and late-onset (LOPE, n010) and early-onset preeclampsia (EOPE, n08). We used the non-selective adenosine receptor agonist (NECA) and the selective agonist (CGS-21680) and/or selective antagonist (ZM-241385) for A 2A AR. Also, the nitric oxide synthase (NOS) inhibitor, L-NAME, was used in co-incubation with CGS-21680. Compared to normal pregnancy, EOPE exhibited low cell proliferation and migration associated with reduced expressions of A 2A AR and VEGF and NO synthesis (i.e., total and phosphorylated serine 1177 endothelial NOS and nitrite formation). In contrast, LOPE exhibited the opposite behavior in all these markers compared to normal pregnancy or EOPE. Cell proliferation and migration were increased by CGS-21680 (or NECA) in all analyzed groups (EOPE>LO-PE>normal pregnancy) compared to their respective basal conditions, an effect that was associated with high NO and VEGF synthesis and blocked by ZM-241385 with significantly different IC 50 for each group (EOPE>LOPE>normal pregnancy). The differences seem independent of gestational age.L-NAME blocked the CGS-21680-mediated cell proliferation and migration in normal pregnancy and LOPE (IC 50 036.2± 2.5 and 8.6±2.2 nM, respectively) as well as the VEGF expression in normal pregnancy. Therefore, the A 2A AR/NO/ VEGF signaling pathway exhibits a pro-angiogenic effect in normal pregnancies and LOPE, whereas impairment in this pathway seems related to the reduced angiogenic capacity of the fetal endothelium in EOPE.

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Association of Preeclampsia in Term Births With Neurodevelopmental Disorders in Offspring

et al. 2020

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reeclampsia is a disorder of abnormal placentation, dysregulated vasculature, and maternal inflammation characterized by new-onset hypertension and organ dysfunction that affects approximately 4% of pregnancies. 1-3 A leading cause of maternal morbidity and mortality, it is associated with adverse maternal outcomes including seizure (eclampsia), stroke, renal failure, and the hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) syndrome, as well as a longterm increase in maternal risk for cardiovascular disease.Preeclampsia has been linked to cerebral palsy, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) in offspring. [4][5][6] In a recent review by Maher and colleagues, 5 evidence was insufficient to draw conclusions about the association of preeclampsia with other neu-rodevelopmental outcomes. Few studies to date have distinguished between term and preterm preeclampsia.Children born to mothers with preeclampsia have alterations in cerebral blood flow and neuronal connectivity and are exposed to abnormal levels of proangiogenic and antiangiogenic factors in utero, supporting a possible causal role for preeclampsia in these outcomes. 7 However, because the definitive treatment for preeclampsia is delivery, it is also a major cause of preterm birth, which may itself adversely affect neurodevelopment. The degree to which preterm birth is a mediator of the association between preeclampsia and neurodevelopment is unclear.We investigated the association between maternal preeclampsia and a range of neurodevelopmental disorders in off-IMPORTANCE Preeclampsia during pregnancy has been linked to an increased risk of cerebral palsy in offspring. Less is known about the role of preeclampsia in other neurodevelopmental disorders.OBJECTIVE To determine the association between preeclampsia and a range of adverse neurodevelopmental outcomes in offspring after excluding preterm births.

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Angiogenic growth factor levels in maternal and fetal blood: correlation with Doppler ultrasound parameters in pregnancies complicated by pre‐eclampsia and intrauterine growth restriction

Abstract: Objectives To correlate levels of angiogenic growth factors with Doppler ultrasound parameters in pregnancies complicated by pre-eclampsia and intrauterine growth restriction (IUGR). Methods

Cited by 94 publications

References 34 publications

Circulating angiogenic factors and their association with birth outcomes in preeclampsia

Circulating angiogenic factors and their association with birth outcomes in preeclampsia

Impaired A2A adenosine receptor/nitric oxide/VEGF signaling pathway in fetal endothelium during late- and early-onset preeclampsia

Association of Preeclampsia in Term Births With Neurodevelopmental Disorders in Offspring

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