scholarly journals Combining Biomarkers to Predict Pregnancy Complications and Redefine Preeclampsia

Hypertension ◽  
2020 ◽  
Vol 75 (4) ◽  
pp. 918-926 ◽  
Author(s):  
Holger Stepan ◽  
Martin Hund ◽  
Theresa Andraczek
Keyword(s):  
Fetal Growth ◽  
Pregnancy Complications ◽  
Fetal Growth Restriction ◽  
Clinical Characteristics ◽  
Angiogenic Factors ◽  
Growth Restriction ◽  
Placental Dysfunction ◽  
Angiogenic Biomarkers ◽  
Plgf Ratio ◽  
New Onset

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.

scholarly journals Placental Dysfunction Underlies Increased Risk of Fetal Growth Restriction and Stillbirth in Advanced Maternal Age Women

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Samantha C. Lean ◽  
Alexander E. P. Heazell ◽  
Mark R. Dilworth ◽  
Tracey A. Mills ◽  
Rebecca L. Jones
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Maternal Age ◽  
Advanced Maternal Age ◽  
Growth Restriction ◽  
Placental Dysfunction ◽  
Increased Risk

Evaluating the Effect of Pravastatin in Early-Onset Fetal Growth Restriction: A Nonrandomized and Historically Controlled Pilot Study

2020 ◽  
Author(s):  
Manel Mendoza ◽  
Raquel Ferrer-Oliveras ◽  
Erika Bonacina ◽  
Pablo Garcia-Manau ◽  
Carlota Rodo ◽  
...  
Keyword(s):  
Pilot Study ◽  
Fetal Growth ◽  
Pregnancy Outcomes ◽  
Fetal Growth Restriction ◽  
Early Onset ◽  
Maternal Serum ◽  
Angiogenic Factors ◽  
Interquartile Range ◽  
Growth Restriction ◽  
Control Group

Objective This study aimed to analyze the effect of pravastatin on angiogenic factors, feto–maternal Doppler findings and pregnancy outcomes in women with early-onset fetal growth restriction (FGR) treated with pravastatin compared with nontreated controls. Study Design This was a pilot study conducted between March 2016 and September 2017. Women with single pregnancies and FGR diagnosed at ≤ 28 weeks of gestation were offered 40 mg of pravastatin daily. Doppler progression, soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) values, and pregnancy outcomes were assessed and compared with consecutive historical controls. Controls were matched to treated women for gestational age, maternal characteristics, maternal and obstetric history, Doppler severity classification, and angiogenic factors at diagnosis. The sFlt-1/PlGF was measured in maternal serum at two different times: before pravastatin was started (ratio M0) and during pravastatin treatment (ratio M1). Doppler severity was classified into four categories: normal, mild, moderate, and severe. Results A total of 38 women were enrolled in this study. No differences were observed in baseline characteristics between groups. However, when compared with the ratio M0, M1 was increased by a median (interquartile range) of 67.0 (−34.8 to 197.3) in the control group but decreased by a median (interquartile range) of −10.1 (−53.1 to −0.07) in the pravastatin treated group (p < 0.001). No significant differences were observed in Doppler progression throughout pregnancy. Median interval from diagnosis to delivery was extended by 16.5 days, the median newborn birthweight was increased from 1,040 to 1,300 g, and the number of women with preeclampsia decreased from 9 (47.4%) to 6 (31.6%) in treated women; however, these trends were not statistically significant. Conclusion In women with early-onset FGR, treatment with pravastatin 40 mg daily was associated with significant improvement in the angiogenic profile. Additionally, median pregnancy duration and median birthweight increased and the incidence of PE was reduced in treated women. Nevertheless, since this pilot study was underpowered, none of these differences were statistically significant. Key Points

scholarly journals Angiogenic Factors in Maternal Circulation and the Risk of Severe Fetal Growth Restriction

2011 ◽  
Vol 173 (6) ◽  
pp. 630-639 ◽  
Author(s):  
B. Olav Asvold ◽  
L. J. Vatten ◽  
P. R. Romundstad ◽  
P. A. Jenum ◽  
S. A. Karumanchi ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Angiogenic Factors ◽  
Growth Restriction ◽  
Maternal Circulation

scholarly journals 497: Angiogenic factors vs. standard evaluation in the prediction of adverse outcome among pregnancies with suspected fetal growth restriction

2018 ◽  
Vol 218 (1) ◽  
pp. S297-S298
Author(s):  
Ofer Beharier ◽  
shani Swissa ◽  
Irit Szaingurten-Solodkin ◽  
Asnat Walfisch ◽  
shimrt Yaniv-Salem ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Adverse Outcome ◽  
Angiogenic Factors ◽  
Growth Restriction

Analysis of placental dysfunction in pregnancies complicated by fetal growth restriction, preeclampsia and HELLP

2006 ◽  
Vol 66 (S 01) ◽  
Author(s):  
MB Langbein ◽  
R Strick ◽  
PL Strissel ◽  
N Vogt ◽  
MW Beckmann ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Growth Restriction ◽  
Placental Dysfunction

scholarly journals Metabolomics Identifies Placental Dysfunction and Confirms Flt-1 (FMS-Like Tyrosine Kinase Receptor 1) Biomarker Specificity

Hypertension ◽  
2019 ◽  
Vol 74 (5) ◽  
pp. 1136-1143 ◽  
Author(s):  
Marie Austdal ◽  
Gabriela Brettas Silva ◽  
Sophie Bowe ◽  
Liv Cecilie Vestrheim Thomsen ◽  
Line Haugstad Tangerås ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Magic Angle Spinning ◽  
Maternal Serum ◽  
Growth Restriction ◽  
Tyrosine Kinase Receptor ◽  
Resonance Spectroscopy ◽  
Magic Angle ◽  
Placental Dysfunction

Clinical end-stage parameters define the pregnancy disorders preeclampsia and fetal growth restriction while classification of the underlying placental dysfunction is missing and urgently needed. Flt-1 (FMS-like tyrosine kinase receptor 1) is the most promising placenta-derived predictive biomarker for preeclampsia. We aimed to classify placental dysfunction in preeclampsia and fetal growth restriction at delivery by metabolic profiling and authenticate the biomarker Flt-1 for placental dysfunction. We studied 143 pregnancies with or without preeclampsia and/or fetal growth restriction delivered by cesarean section. Metabolic placenta profiles were created by high-resolution magic angle spinning nuclear magnetic resonance spectroscopy and the resulting placental phenotypes obtained by hierarchical clustering. Placental Flt-1 expression (membrane-bound and soluble isoforms combined) and maternal serum Flt-1 expression (soluble isoforms) were analyzed by immunohistochemistry and ELISA, respectively. We identified 3 distinct placenta groups by 21 metabolites and diagnostic outcome parameters; normal placentas, moderate placental dysfunction, and severe placental dysfunction. Increased placental Flt-1 was associated with severe placental dysfunction, and increased serum Flt-1 was associated with moderate and severe placental dysfunction. The preeclamptic pregnancies with and without placental dysfunction could be distinguished by 5 metabolites and placental Flt-1. Placental Flt-1 alone could separate normal pregnancies with and without placental dysfunction. In conclusion, metabolomics could classify placental dysfunction and provide information not identified by traditional diagnostics and metabolites with biomarker potential were identified. Flt-1 was confirmed as precision biomarker for placental dysfunction, substantiating its usefulness for identification of high-risk pregnancies for preeclampsia and fetal growth restriction with placental involvement.

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