Increased Placental sFLT1 (Soluble fms-Like Tyrosine Kinase Receptor-1) Drives the Antiangiogenic Profile of Maternal Serum Preceding Preeclampsia but Not Fetal Growth Restriction

Gaccioli, Francesca; Sovio, Ulla; Gong, Sungsam; Charnock-Jones, D. Stephen; Smith, Gordon C. S.

doi:10.1161/hypertensionaha.122.19482

Cited by 15 publications

(11 citation statements)

References 39 publications

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“…Maternal biochemical markers fundamentally reflect placental function 30 . In recent years, PlGF, sFlt-1 and the sFlt-1/PlGF ratio have become popular markers for evaluating placental insufficiency 31 . We found that lower levels of PlGF were associated with a higher risk of FGR, which is consistent with previous research 15,32,33 .…”

Section: Discussionmentioning

confidence: 99%

Construction of prediction model for fetal growth restriction during first trimester in an Asian population

Zheng,

Ji,

Wang

et al. 2024

Ultrasound in Obstet & Gyne

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ObjectiveTo construct a prediction model for fetal growth restriction (FGR) during the first trimester (11‐13+6 weeks) and evaluate its screening performance.MethodsSingle pregnancies who underwent the first trimester (11‐13+6 weeks) ultrasound screening at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2019 to April 2022 were selected as prospective study subjects. Basic clinical information, ultrasound indicators, and serum indicators of pregnant women were collected. Fetal weight assessment was based on the fetal growth curve of the Southern Chinese population, and the definition of FGR was based on standards developed through the Delphi process. The least absolute shrinkage and selection operator (LASSO) regression method was used to select optimal features and analyze the predictive value of each indicator in the model. Finally, the model was constructed, and its discrimination, effectiveness, and clinical usefulness were evaluated.ResultsA total of 1188 pregnant women were included in the final statistical analysis, of whom 108 had FGR. LASSO regression identified 7 predictive features, including a history of maternal hypertension, maternal smoking or passive smoking history, number of pregnancies, uterine artery pulsatility index (UtA PI), ductus venosus pulsatility index (DV PIV), placental growth factor multiples of the median (PlGF MOM), and soluble fms‐like tyrosine kinase‐1 (sFlt‐1) MOM. The nomogram prediction model constructed based on the above predictors predicted FGR more accurately, and the area under the curve (AUC) in the validation cohort was 0.82 (95%CI: 0.74‐0.90). The calibration curve and Hosmer‐Lemeshow test demonstrated good calibration of the model, while the clinical decision curve and clinical impact curve conclusively support its practical value in the clinical setting.ConclusionThe multi‐index prediction model constructed during the first trimester is feasible and has good predictive value.This article is protected by copyright. All rights reserved.

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Section: Discussionmentioning

confidence: 99%

Construction of prediction model for fetal growth restriction during first trimester in an Asian population

Zheng,

Ji,

Wang

et al. 2024

Ultrasound in Obstet & Gyne

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“…In a recent publication, Gaccioli et al [ 75 ] showed that although the sFlt-1/PlGF ratio was increased in both pre-eclampsia and FGR in both placenta and maternal serum, in pre-eclampsia the sFlt-1/PlGF ratio was strongly associated with placental sFlt-1 concentrations ( r =0.45; P <0.0001) but not placental PlGF concentrations ( r =−0.17; P =0.16). In FGR pregnancies, however, the sFlt-1/PlGF ratio was strongly associated with placental PlGF concentrations ( r =−0.35; P =0.02) but not placental sFlt-1 concentrations ( r =0.04; P =0.81) suggesting that in pre-eclampsia the elevated sFlt-1/PlGF ratio is primarily driven by increased placental sFlt-1, whereas in FGR, it is mainly due to decreased placental PlGF.…”

Section: Angiogenic Factorsmentioning

confidence: 99%

Circulating biomarkers associated with placental dysfunction and their utility for predicting fetal growth restriction

Hong

Kumar

2023

Clinical Science

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Fetal growth restriction (FGR) leading to low birth weight (LBW) is a major cause of neonatal morbidity and mortality worldwide. Normal placental development involves a series of highly regulated processes involving a multitude of hormones, transcription factors, and cell lineages. Failure to achieve this leads to placental dysfunction and related placental diseases such as pre-clampsia and FGR. Early recognition of at-risk pregnancies is important because careful maternal and fetal surveillance can potentially prevent adverse maternal and perinatal outcomes by judicious pregnancy surveillance and careful timing of birth. Given the association between a variety of circulating maternal biomarkers, adverse pregnancy, and perinatal outcomes, screening tests based on these biomarkers, incorporating maternal characteristics, fetal biophysical or circulatory variables have been developed. However, their clinical utility has yet to be proven. Of the current biomarkers, placental growth factor and soluble fms-like tyrosine kinase 1 appear to have the most promise for placental dysfunction and predictive utility for FGR.

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“…In a more recent paper, Gaccioli [ 48 ] found that the triggers responsible for increasing the sFlt-1/PlGF ratio are different in pre-eclampsia than fetal growth restriction: in pre-eclampsia, sFlt-1 displays increased concentrations in the placenta, leading to the elevated sFlt-1/PlGF ratio, whereas in fetal growth restriction, reduced placental expression of PlGF causes the elevated sFlt-1/PlGF ratio. Moreover, among patients already diagnosed with early fetal growth restriction (<32 weeks), Palma Dos Reis [ 49 ] demonstrated that sFlt-1/PLGF values > 85 measured when the diagnosis was established were associated with a shorter time until delivery (1.9 ± 1.52 weeks vs. 5.7 ± 3.2 weeks for sFlt-1/PlGF ≤ 85), as well as higher prevalence of fetal demise, albeit independently of pre-eclampsia.…”

Section: Relevant Data From the Recent Literature Regarding The Value...mentioning

confidence: 99%

The Current Role of the sFlt-1/PlGF Ratio and the Uterine–Umbilical–Cerebral Doppler Ultrasound in Predicting and Monitoring Hypertensive Disorders of Pregnancy: An Update with a Review of the Literature

Chirilă,

Mărginean,

Chirilă

et al. 2023

Children

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Regarding the hypertensive disorders of pregnancy, pre-eclampsia (PE) remains one of the leading causes of severe and life-threatening maternal and fetal complications. Screening of early-onset PE (<34 weeks of pregnancy), as well as late-onset PE (≥34 weeks), shows poor performance if based solely on clinical features. In recent years, biochemical markers from maternal blood—the pro-angiogenic protein placental growth factor (PlGF) and the antiangiogenic protein soluble FMS-like tyrosine kinase 1 (sFlt-1)—and Doppler velocimetry indices—primarily the mean uterine pulsatility index (PI), but also the uterine resistivity index (RI), the uterine systolic/diastolic ratio (S/D), uterine and umbilical peak systolic velocity (PSV), end-diastolic velocity (EDV), and uterine notching—have all shown improved screening performance. In this review, we summarize the current status of knowledge regarding the role of biochemical markers and Doppler velocimetry indices in early prediction of the onset and severity of PE and other placenta-related disorders, as well as their role in monitoring established PE and facilitating improved obstetrical surveillance of patients categorized as high-risk in order to prevent adverse outcomes. A sFlt-1/PlGF ratio ≤ 33 ruled out early-onset PE with 95% sensitivity and 94% specificity, whereas a sFlt-1/PlGF ≥88 predicted early-onset PE with 88.0% sensitivity and 99.5% specificity. Concerning the condition’s late-onset form, sFlt-1/PlGF ≤ 33 displayed 89.6% sensitivity and 73.1% specificity in ruling out the condition, whereas sFlt-1/PlGF ≥ 110 predicted the condition with 58.2% sensitivity and 95.5% specificity. The cut-off values of the sFlt-1/PlGF ratio for the screening of PE were established in the PROGNOSIS study: a sFlt-1/PlGF ratio equal to or lower than 38 ruled out the onset of PE within one week, regardless of the pregnancy’s gestational age. The negative predictive value in this study was 99.3%. In addition, sFlt-1/PlGF > 38 showed 66.2% sensitivity and 83.1% specificity in predicting the occurrence of PE within 4 weeks. Furthermore, 2018 ISUOG Practice Guidelines stated that a second-trimester mean uterine artery PI ≥ 1.44 increases the risk of later PE development. The implementation of a standard screening procedure based on the sFlt-1/PlGF ratio and uterine Doppler velocimetry may improve early detection of pre-eclampsia and other placenta-related disorders.

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Increased Placental sFLT1 (Soluble fms-Like Tyrosine Kinase Receptor-1) Drives the Antiangiogenic Profile of Maternal Serum Preceding Preeclampsia but Not Fetal Growth Restriction

Cited by 15 publications

References 39 publications

Construction of prediction model for fetal growth restriction during first trimester in an Asian population

Construction of prediction model for fetal growth restriction during first trimester in an Asian population

Circulating biomarkers associated with placental dysfunction and their utility for predicting fetal growth restriction

The Current Role of the sFlt-1/PlGF Ratio and the Uterine–Umbilical–Cerebral Doppler Ultrasound in Predicting and Monitoring Hypertensive Disorders of Pregnancy: An Update with a Review of the Literature

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