Predictive value of sFlt-1, PlGF, sFlt-1/PlGF ratio and PAPP-A for late-onset preeclampsia and IUGR between 32 and 37 weeks of pregnancy

Birdir, C; Droste, Leonie; Fox, L; Frank, Mirjam; Fryze, J; Enekwe, A; Köninger, Angela; Kimmig, Rainer; Schmidt, Börge; Gellhaus, Alexandra

doi:10.1016/j.preghy.2018.04.010

Cited by 57 publications

(49 citation statements)

References 21 publications

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“…Vascular abnormalities during pregnancy change angiogenic markers such as Flt-1 and PIGF [34]. These markers and their ratio are important in clinical monitoring of patients with preeclampsia, and they are used on a regular basis [35][36][37]. The Flt-1/PIGF ratio is increasingly used in the study of restricted intrauterine growth [38].…”

Section: Discussionmentioning

confidence: 99%

Increased Angiogenesis and Lymphangiogenesis in the Placental Villi of Women with Chronic Venous Disease during Pregnancy

Ortega

Sáez

Fraile-Martínez

et al. 2020

IJMS

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Pregnancy is a period in a woman’s life associated with an increased risk of developing lower extremity chronic venous disease (CVD). Pregnancy-associated CVD is associated with changes in placental villi. We investigated angiogenesis and lymphangiogenesis in the placental villi of women with CVD during pregnancy compared with healthy controls with no history of CVD (HC). An observational, analytical, and prospective cohort study was conducted on 114 women in their third trimester of pregnancy (32 weeks). Sixty-two participants were clinically diagnosed with CVD. In parallel, 52 controls with no history of CVD (HC) were studied. Gene and protein expression of CD31, podoplanin (D2-40), Flt-1, and placental growth factor (PIGF) was analysed by real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry. CD31 and D2-40 gene expression was significantly greater in the placental villi of women with CVD, as were the numbers of vessels positive for CD31 and D2-40. Significantly higher gene and protein expression of Flt-1 and PIGF was observed in the placental villi of women with CVD. Histological analysis showed more placental villi with periodic acid of Schiff (PAS)-positive material in women with CVD. Our results show a connection between pregnancy-associated CVD and leading to higher proangiogenic and lymphangiogenic activity in placental villi.

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Section: Discussionmentioning

confidence: 99%

Increased Angiogenesis and Lymphangiogenesis in the Placental Villi of Women with Chronic Venous Disease during Pregnancy

Ortega

Sáez

Fraile-Martínez

et al. 2020

IJMS

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“…1,3,13,14,16,[34][35][36][37][38] The majority of studies recruited patients with SGA as outcome. [1][2][3][4][13][14][15][16][21][22][23]25,26,[28][29][30][31][32][33][34][35][36][37][38] The definition for SGA was lower than the 10th birthweight percentiles upper reference limit in 18 studies. 3,4,[13][14][15][16][21][22][23]25,26,[29][30][31][32]34,35,…”

Section: Study and Data Selectionmentioning

confidence: 99%

“…10 At this moment, there is no conclusive evidence that measuring maternal angiogenic biomarkers are (also) useful in the clinical management of fetal growth restriction. Despite many studies linking maternal angiogenic concentrations to the neonatal outcomes (mainly SGA), 3,[11][12][13][14][15][16] there is no systematic review of the predictive performance of PlGF, sFlt-1 and sFlt-1/PlGF ratio at different trimesters of pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Role of sFlt-1 and PlGF in the screening of small-for-gestational age neonates during pregnancy: A systematic review

et al. 2019

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Background Fetal growth restriction, i.e. the restriction of genetically predetermined growth potential due to placental dysfunction, is a major cause of neonatal morbidity and mortality. The consequences of inadequate fetal growth can be life-long, but the risks can be reduced substantially if the condition is identified prenatally. Currently, screening strategies are based on ultrasound detection of a small-for-gestational age fetus and do not take into account the underlying vascular pathology in the placenta. Measurement of maternal circulating angiogenic biomarkers placental growth factor, sFlt-1 (soluble FMS-like tyrosine kinase-1) are increasingly used in studies on fetal growth restriction as they reflect the pathophysiological process in the placenta. However, interpretation of the role of angiogenic biomarkers in prediction of fetal growth restriction is hampered by the varying design, population, timing, assay technique and cut-off values used in these studies. Methods We conducted a systematic-review in PubMed (MEDLINE), EMBASE (Ovid) and Cochrane to explore the predictive performance of maternal concentrations of placental growth factor, sFlt-1 and their ratio for fetal growth restriction and small-for-gestational age, at different gestational ages, and describe the longitudinal changes in biomarker concentrations and optimal discriminatory cut-off values. Results We included 26 studies with 2514 cases with small-for-gestational age, 27 cases of fetal growth restriction, 582 cases mixed small-for-gestational age/fetal growth restriction and 29,374 reference. The largest mean differences for the two biomarkers and their ratio were found after 26 weeks of gestational age and not in the first trimester. The ROC-AUC varied between 0.60 and 0.89 with sensitivity and specificity matching the different cut-off values or a preset false-positive rate of 10%. Conclusions Most of the studies did not make a distinction between small-for-gestational age and fetal growth restriction, and therefore the small-for-gestational age group consists of fetuses with growth restriction and fetuses that are constitutionally normal. The biomarkers can be a valuable screening tool for small-for-gestational age pregnancies, but unfortunately, there is not yet a clear cut-off value to use for screening. More research is needed to see if these biomarkers are sufficiently able to differentiate growth restriction on their own and how these biomarkers in combination with other relevant clinical and ultrasound parameters can be used in clinical routine diagnostics.

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“…Одним из возможных решений мог бы быть расчет иных пороговых уровней подтверждения и прогноза ПЭ у пациенток с ожирением на основании более обширных исследований, если придерживаться мнения, что ожирение повышает чувствительность эндотелия к дисбалансу факторов ангиогенеза, тем самым снижая порог развития ПЭ [31]. Так, в одном из исследований уровня sFlt-1/PigF среди пациенток с поздней ПЭ и повышенным иМТ был рассчитан порог 57 ед с чувствительностью 84 % и специфичностью 93 % [32].…”

Section: Discussionunclassified

Preeclampsia features in pregnancy with gestational diabetes mellitus

Bettikher¹,

Dedov²,

Popova³

et al. 2019

Z.akus.zen.bolezn

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Hypothesis/aims of study. The high prevalence of gestational diabetes mellitus (GDM) and the social importance of preeclampsia (PE) due to massive perinatal morbidity and mortality, as well as the high rate of PE in GDM pregnancy define the need to study the characteristics of pregnancy course in these women to develop the prevention and management of pregnancy complication. This study aimed at evaluating clinical and laboratory features of PE in GDM pregnancy. Study design, materials and methods. According to the inclusion criteria, 112 pregnant women were enrolled in this prospective cohort study after 24 weeks of gestation: with GDM and PE (n = 24), with PE (n = 22); with GDM (n = 37), without studied pregnancy complications (n = 37). We assessed serum levels of placental growth factor (PIGF) and soluble FMS-like tyrosine kinase-1 (sFlt-1). Pregnancy course and labour were evaluated using medical history. Results. Severe PE developed more often (p = 0.0014, Chi-square test) in the PE group (59%, n = 13) compared to the GDM + PE group (13%, n = 3). Elective preterm labour occurred more often in the PE group compared to other study groups (PE: 23%, n = 5; GDM + PE: 9%, n = 2; p 0.0001, Chi-square test with Yates correction), which is in line with the severity of PE in this group. The rate of preterm labour did not differ between the GDM + PE group and the group without studied pregnancy complications. Moreover, the mean fasting glucose level was higher in the GDM group compared to the GDM + PE group (p = 0.01, MannWhitney test). The GDM + PE group was characterized by fasting hyperglycemia episodes and a basal insulin regimen, while the GDM group by postprandial glucose peaks, and a bolus insulin regimen. Women with GDM + PE were notable for the high pre-pregnancy body mass index (29.0 6.58 kg/m2), and a family history of DM was more typical for women with GDM without PE (59%, n = 19). The sFlt-1/PIGF ratio did not differ between the GDM + PE, GDM and control groups and was lower compared to the PE group (p 0.0001, Fishers LSD test). PIGF level was not different in the GDM + PE and GDM groups, but was lower compared to the control group. Conclusion. Our study showed that PE in women with GDM is more benign than in patients without GDM, taking into account both clinical and laboratory signs. At the same time, obesity appears to be one of the most important risk factors for the both pregnancy complications. The data of this study, in addition to those described in the literature, suggest that initial carbohydrate disorders play a disease-limiting, protective role in a vicious cycle of PE due to angiogenesis stimulation. The use of angiogenesis factors as markers of PE in GDM patients is limited, which requires further research.

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Predictive value of sFlt-1, PlGF, sFlt-1/PlGF ratio and PAPP-A for late-onset preeclampsia and IUGR between 32 and 37 weeks of pregnancy

Cited by 57 publications

References 21 publications

Increased Angiogenesis and Lymphangiogenesis in the Placental Villi of Women with Chronic Venous Disease during Pregnancy

Increased Angiogenesis and Lymphangiogenesis in the Placental Villi of Women with Chronic Venous Disease during Pregnancy

Role of sFlt-1 and PlGF in the screening of small-for-gestational age neonates during pregnancy: A systematic review

Preeclampsia features in pregnancy with gestational diabetes mellitus

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Predictive value of sFlt-1, PlGF, sFlt-1/PlGF ratio and PAPP-A for late-onset preeclampsia and IUGR between 32 and 37 weeks of pregnancy

Cited by 57 publications

References 21 publications

Increased Angiogenesis and Lymphangiogenesis in the Placental Villi of Women with Chronic Venous Disease during Pregnancy

Increased Angiogenesis and Lymphangiogenesis in the Placental Villi of Women with Chronic Venous Disease during Pregnancy

Role of sFlt-1 and PlGF in the screening of small-for-gestational age neonates during pregnancy: A systematic review

Preeclampsia features in pregnancy with gestational diabetes mellitus

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Predictive value of sFlt-1, PlGF, sFlt-1/PlGF ratio and PAPP-A for late-onset preeclampsia and IUGR between 32 and 37 weeks of pregnancy