Abstract
Placental dysfunction underlies a spectrum of perinatal pathologies, including preeclampsia and fetal growth restriction. Angiogenesis-related factors, including sFlt-1 (soluble fms-like tyrosine kinase 1) and PlGF (placental growth factor), play an important role in placental dysfunction; altered levels are detectable several weeks before onset of pregnancy complications. In vitro diagnostic tests for these biomarkers can improve early diagnosis and facilitate prediction of maternal and fetal outcomes. We assessed evidence for combining angiogenic biomarkers with other biomarkers or clinical parameters to predict maternal/fetal outcomes in pregnant women with placental dysfunction. Pooled information on placental perfusion (ultrasonography, mean arterial pressure), clinical characteristics, and biomarker levels (PlGF) can improve first-trimester prediction and preeclampsia diagnosis. Angiogenic factors (sFlt-1/PlGF ratio; PlGF alone) with or without clinical characteristics can facilitate second-/third-trimester prediction of early-onset and late-onset preeclampsia. A combination of increased sFlt-1/PlGF ratio and ultrasound can rule out early fetal growth restriction. The sFlt-1/PlGF ratio is also a reliable tool for discriminating between pregnancy-related hypertensive disorders, including superimposed preeclampsia and gestational hypertension. Analysis of angiogenic factors with or without uterine Doppler substantially improves sensitivity and specificity for predicting adverse outcomes and iatrogenic preterm delivery. We propose to extend the American College of Obstetricians and Gynecologists definition of preeclampsia in the future to include the combination of new-onset hypertension and new-onset of altered angiogenic factors (sFlt-1/PlGF ratio or PlGF alone). In summary, altered angiogenic biomarkers indicate placental dysfunction, and their implementation into clinical practice will help reduce the considerable burden of morbidity and mortality associated with adverse pregnancy outcomes as a consequence of angiogenic-placental syndrome.
Highlights
Placental dysfunction underlies a spectrum of perinatal pathologies, including preeclampsia and fetal growth restriction
Evidence from a systematic review of early-onset preeclampsia studies showed that the majority of preeclampsia cases had a normal placenta and that villous lesions were present in a proportion of normal pregnancies.[5]
Several angiogenic factors play an important role in Placental dysfunction (PD): VEGF-A is essential for placental vascular development, affecting proliferation and migration of endothelial cells and vascular permeability; PlGF, a proangiogenic VEGF family member, is abundantly expressed in the placenta and acts by enhancing the action of VEGF-A; sFlt-1, an antiangiogenic VEGF family member, is important in the regulation of angiogenic homeostasis during pregnancy. sFlt-1 and PlGF are expressed in the placenta and extra-placentally, in vascular endothelial cells, fibroblasts, osteoblasts, smooth muscle cells, and monocytes.[4]
Summary
Preeclampsia is a hypertensive syndrome affecting 2% to 3% of pregnancies and characterized by endothelial damage in multiple organs (Figure 2).[10,11,12] The definition of preeclampsia previously included hypertension plus proteinuria after 20 weeks’ gestation and has expanded to include hypertension in combination with renal and liver dysfunction and thrombocytopenia (Table 1).[10,11,13] Proteinuria is no longer necessary to fulfill the definition of preeclampsia. The Fetal Medicine Foundation algorithm combines information on risk factors, such as placental perfusion (uterine artery pulsatility index [UtA-PI] plus mean arterial pressure), clinical characteristics (maternal factors/medical history), and biomarker levels (PlGF), to estimate risk for preeclampsia. Considerable evidence supports this combined approach,[20,21,22,23,24] including 3 largescale prospective cohort studies in women who attended their routine first hospital visit at 11 to 13 weeks’ gestation.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
