Angiogenic factors for the prediction of preeclampsia in high-risk women

Simas, Tiffany A. Moore; Crawford, Sybil L.; Solitro, Matthew J.; Frost, Sara; Meyer, Bruce A.; Maynard, Sharon E.

doi:10.1016/j.ajog.2007.06.030

Cited by 154 publications

(52 citation statements)

References 19 publications

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“…The supplemental table compares the test characteristics of the sFLT-1/PlGF ratio of various studies (Additional file 1: Table S1). The prospective cohort study by Moore Simas and colleagues included only patients with at least one risk factor for PE in their medical history [43]. In this study, the determination of sFLT-1 showed a good predictive accuracy for early-onset PE, with an AUC value of 0.90 (95% CI 0.78–1.0) between 22 and 26 weeks of gestation.…”

Section: Discussionmentioning

confidence: 94%

Prediction of preeclampsia and induced delivery at <34 weeks gestation by sFLT-1 and PlGF in patients with abnormal midtrimester uterine Doppler velocimetry: a prospective cohort analysis

Stubert

Ullmann

Bolz

et al. 2014

BMC Pregnancy Childbirth

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BackgroundWomen with bilateral abnormal uterine artery Doppler velocimetry (UtADV) are at increased risk for an adverse pregnancy outcome. This study aimed to determine if additional assessment of midtrimester angiogenic factors improves the predictive accuracy of Doppler results for various outcome parameters.MethodsWomen with a bilateral abnormal UtADV, which was defined as a postsystolic incision and/or an increased pulsatility index greater than the 95th centile, and a singleton pregnancy were prospectively recruited between 19 + 0 and 26 + 6 weeks of gestation. Maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLT-1) were measured with a fully automated immunoassay and their ratio was calculated.ResultsAngiogenic factors could predict the development of preeclampsia (PE), as well as induced delivery at <34 weeks of gestation, but failed to predict the development of normotensive intrauterine growth restriction. Twelve (24.0%) of the 50 recruited women developed PE. Nine of these patients had early-onset disease (<34 + 0 weeks). Six (12.0%) patients were delivered at <34 + 0 weeks. The most useful test results in the prediction of PE and induced delivery at <34 + 0 weeks were observed using the sFLT-1/PlGF >95th centile ratio with a sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of 66.7%, 89.5%, 66.7%, and 89.5% for PE, and 85.7%, 86.1%, 50.1%, and 97.4% for induced delivery, respectively. Positive and negative likelihood ratios were 6.33 (95% CI 2.31–17.38) and 0.37 (95% CI 0.17–0.84) for PE, and 6.14 (95% CI 2.76–13.69) and 0.17 (0.03–1.02) for induced delivery, respectively. Corresponding odds ratios were 17.0 (95% CI 3.5–83.0) and 37.0 (95% CI 3.8–363.9), respectively.ConclusionsMeasurement of angiogenic factors improves the specificity of an abnormal UtADV for prediction of PE. Compared with prediction of PE an abnormal sFLT-1/PlGF ratio revealed higher sensitivity for prediction of induced delivery at <34 + 0 weeks. The NPV of 97% will help to reassure most patients with an abnormal UtADV and a normal sFLT-1/PlGF ratio.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2393-14-292) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 94%

Prediction of preeclampsia and induced delivery at <34 weeks gestation by sFLT-1 and PlGF in patients with abnormal midtrimester uterine Doppler velocimetry: a prospective cohort analysis

Stubert

Ullmann

Bolz

et al. 2014

BMC Pregnancy Childbirth

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“…Yet, the difference in circulatory PlGF between normotensive pregnancies and those affected by preeclampsia is the highest within weeks of the onset of the clinical symptoms. As with sFlt-1, the pre-symptomatic levels of circulatory PlGF is thought to associate with the severity or time of onset of preeclampsia [7]. Urinary PlGF is likewise lower in preeclamptic patients before and at the time of symptoms [8, 9].…”

Section: Introductionmentioning

confidence: 99%

Correlation between cell-free mRNA expressions and PLGF protein level in severe preeclampsia

et al. 2015

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BackgroundPreeclampsia is a major cause of morbidity and mortality, both maternal and perinatal. The etiology and pathophysiology of preeclampsia remain unknown. Research shows the implantation of the placenta in preeclampsia occurs due to incomplete angiogenic imbalance as one of the preeclampsia pathogenesis. PlGF is angiogenic protein which is synthesized in placenta by mRNA PlGF. When damage occurs, mRNA will be released from cell and form cell-free mRNA. This study aims to analyze the differences between the PlGF mRNA expression in severe preeclampsia and normal pregnancy as well as to measure the relationship between cell-free mRNA and levels of PlGF with the incidence of severe preeclampsia.MethodsThe method used in this study is an observational analytic study with cross-sectional design. Blood samples were obtained from patients with preeclampsia and normal pregnancies as the controlling factors in accordance with inclusion and exclusion criterias. Examination of the PlGF level was measured by ELISA method and mRNA PIGF expression was measured by RT-PCR. Physical and laboratory examinations of patients were recorded and collected as data. Calculations were done by statistical analysis.ResultsMean of the cell-free mRNA PlGF expression level in severe preeclampsia is 2.2983 ng/mL within the scale of 1.96–2.83 ng/mL and deviation standard of 0.1897. Using Pearson Analysis Test, the result shows that there is a positive correlation between cell-free mRNA expression and PlGF protein level in severe preeclampsia, with r = 0.640 dan p < 0.004.ConclusionThere is no difference between expression of cell-free mRNA PlGF in severe preeclampsia serum and normal pregnancy. There is a significant correlation between expression of cell-free mRNA and PlGF protein level in severe preeclampsia.

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“…Numerous case-control [12, 14, 16, 17] as well as prospective studies [4, 8, 15] have highlighted the role of the measurement of plasma sFlt-1 and PlGF in pregnant women as a diagnostic and predictive test for PE. Our group recently showed that an elevated sFlt-1/PlGF ratio as assessed by automated Elecsys® assay allows the determination of PE in the clinical routine context [19].…”

Section: Introductionmentioning

confidence: 99%

The course of angiogenic factors in early- vs. late-onset preeclampsia and HELLP syndrome

Schaarschmidt

Rana

Stepan

2013

Journal of Perinatal Medicine

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Aims Preeclampsia (PE) is considered a uniformly progressive disease, however, it shows a different pattern of clinical progression in patients with early (<34 weeks) or late (≥34 weeks) onset of the disease. Angiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) are closely related to the clinical course of PE. We evaluated sFlt-1 and PlGF levels in the clinical course of PE in women admitted with a diagnosis of PE at different gestational ages. Methods This retrospective study included 34 patients with PE, of which 11 patients had HELLP syndrome (over a period of 3 years). Serial measurements of sFlt-1 and PlGF were completed from admission until delivery. Values are presented as mean±standard deviation. Results Mean gestational age of admission among women with early onset PE was significantly lower, at 29±3 weeks compared to 37±1 weeks among patients with late onset disease. Mean prolongation of pregnancy was 6 days, which was similar within the two groups. Compared to women with late onset PE, women with early-onset PE had a greater increase in sFlt-1 (11% vs. 3% per day, P<0.05), greater decrease in PlGF levels (21% vs. 10% per day, P=0.30), resulting in a much higher increase in sFlt-1/PlGF ratio (23% vs. 8% per day, P<0.05). Patients with HELLP syndrome showed comparable progression patterns. Conclusion In a similar way to the progressively worsening clinical course observed in women with early onset PE, there were changes in the angiogenic profile that leads to a more anti-angiogenic state in these women with each passing day. These findings may have implications in identification of the women for appropriate patient management and possible future therapies based on the reduction of sFlt-1 levels.

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Angiogenic factors for the prediction of preeclampsia in high-risk women

Cited by 154 publications

References 19 publications

Prediction of preeclampsia and induced delivery at <34 weeks gestation by sFLT-1 and PlGF in patients with abnormal midtrimester uterine Doppler velocimetry: a prospective cohort analysis

Prediction of preeclampsia and induced delivery at <34 weeks gestation by sFLT-1 and PlGF in patients with abnormal midtrimester uterine Doppler velocimetry: a prospective cohort analysis

Correlation between cell-free mRNA expressions and PLGF protein level in severe preeclampsia

The course of angiogenic factors in early- vs. late-onset preeclampsia and HELLP syndrome

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