Angiogenic factors: potential to change clinical practice in pre‐eclampsia?

Cerdeira, Ana Sofia; Agrawal, Swati; Staff, Anne Cathrine; Redman, Christopher W.G.; Vatish, Manu

doi:10.1111/1471-0528.15042

Cited by 61 publications

(39 citation statements)

References 91 publications

(117 reference statements)

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“…Another study in an upper middle income country (Mexico), similar to South Africa in income ranking, also showed an elevated sFlt-1/PIGF ratio in sPE [11]. Novel therapies used in managing PE aim at reversing this angiogenic imbalance [21, 59, 60] which is usually worse in EOPE than LOPE [61] as demonstrated in the present study. Importantly, significant angiogenic imbalance occurs in both EOPE and LOPE and this explains the use of sFlt-1/PIGF ratio ≥ 85 and ≥110 to diagnose EOPE and LOPE respectively [21, 62–64] when there is clinical suspicion but doubtful diagnosis (with the greatest ability of the test being its high negative predictive value) [65, 66].…”

Section: Discussionsupporting

confidence: 79%

The performance of pre-delivery serum concentrations of angiogenic factors in predicting postpartum antihypertensive drug therapy following abdominal delivery in severe preeclampsia and normotensive pregnancy

2019

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Background The imbalance between circulating concentrations of anti- and pro-angiogenic factors is usually intense in preeclampsia with severe features (sPE). It is possible that pre-delivery circulating levels of angiogenic factors in sPE may be associated with postpartum antihypertensive drug requirements. Objective To determine the predictive association between maternal pre-delivery serum concentrations of angiogenic factors and the use of ≥3 slow- and/or a rapid-acting antihypertensive drug therapy in sPE on postpartum days zero to three following caesarean delivery. Study design Women with sPE (n = 50) and normotensive pregnancies (n = 90) were recruited prior to childbirth. Serum samples were obtained from each participant < 48 hours before delivery to assess the concentrations of placental growth factor (PIGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) using the Roche Elecsys platform. Each participant was followed up on postpartum days zero, one, two and three to monitor BP and confirm antihypertensive treatment. The optimal cut-off thresholds of sFlt-1/PIGF ratio from receiver operating characteristic curve predictive of the antihypertensive therapy were subjected to diagnostic accuracy assessment. Results The majority 58% (29/50) of sPE had multiple severe features of preeclampsia in the antenatal period with the commonest presentation being severe hypertension in 88% (44/50) of this group, followed by features of impending eclampsia which occurred in 42% (21/50). The median gestational age at delivery was 38 (Interquartile range, IQR 1) vs 36 (IQR 6) weeks, p < 0.001 in normotensive and sPE groups respectively. Notably, the median sFlt-1/PIGF ratio in normotensive and sPE groups were 7.3 (IQR 17.9) and 179.1 (IQR 271.2) respectively, p < 0.001. Of the 50 sPE participants, 34% (17/50) had early-onset preeclampsia. The median (IQR) of sFlt-1/PIGF in the early- and late-onset preeclampsia groups were 313.52 (502.25), and 166.59(195.37) respectively, p = 0.006. From postpartum days zero to three, 48% (24/50) of sPE received ≥ 3 slow- and/or a rapid-acting antihypertensive drug. However, the daily administration of ≥ 3 slow- and/or a rapid-acting antihypertensive drug in sPE were pre-delivery 26% (13/50), postpartum day zero 18% (9/50), postpartum day one 34% (17/50), postpartum day two 24% (12/50) and postpartum day three 20% (10/50). In sPE, the pre-delivery sFlt-1/PIGF ratio was predictive of administration of ≥3 slow- and/or a rapid-acting antihypertensive drug on postpartum days zero, one and two with the optimal cut-off ratio being ≥315.0, ≥181.5 and ≥ 267.8 respectively (sensitivity 72.7–75.0%, specificity 64.7–78.6%, positive predictive value 40.0–50.0% and negative predictive value 84.6% - 94.3%). The predictive performance of sFlt-1/PIG ratio on postpartum day 3 among the sPE was no...

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Section: Discussionsupporting

confidence: 79%

The performance of pre-delivery serum concentrations of angiogenic factors in predicting postpartum antihypertensive drug therapy following abdominal delivery in severe preeclampsia and normotensive pregnancy

2019

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“…Numerous studies have demonstrated the value of both sFlt-1 and PlGF in the short-term prediction, diagnosis and evolution of pre-eclampsia [48][49][50][51][52] and their use as a ratio (sFlt-1/PlGF) in the diagnosis of early-and late-onset pre-eclampsia has also been investigated. A multicenter case-control study, including a total of 1149 women with singleton pregnancy (of whom 877 were used to construct normal ranges for the sFlt-1/PlGF ratio throughout pregnancy), compared 234 women with pre-eclampsia with a matched cohort of 468 women with normal pregnancy outcome 53 .…”

Section: Predictive Value Of Sflt-1 and Plgfmentioning

confidence: 99%

From first‐trimester screening to risk stratification of evolving pre‐eclampsia in second and third trimesters of pregnancy: comprehensive approach

Poon

Galindo

Surbek

et al. 2020

Ultrasound in Obstet & Gyne

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“…Verlohren et al demonstrated high sensitivity and specificity of sFlt-1/PlGF ratio ≤33 for ruling out women with suspected preeclampsia, and sFlt-1/PlGF ratios ≥85 and ≥110 for ruling in women with suspected preeclampsia in the early and late gestational phase, respectively [10]. In a meta-analysis of six studies (including that of Verlohren et al [10]), Cerdeira et al further demonstrated high pooled sensitivity and specificity for these cut-offs [9]. For ruling out preeclampsia within 4 weeks in women with suspected preeclampsia, a sFlt-1/PlGF cut-off of ≤38 was validated [11,12].…”

Section: Introductionmentioning

confidence: 99%

“…Clinical use of gestational age-specific sFlt-1/PlGF cut-offs to aid in the prediction and diagnosis of preeclampsia is increasing [9]. There are several commercially available electrochemiluminescence immunoassays for the determination of sFlt-1 and PlGF concentrations in serum, including the Roche Elecsys ® (Roche Diagnostics, Mannheim, Germany) and BRAHMS Kryptor (Thermo Fisher Scientific, Hennigsdorf, Germany) sFlt-1 and PlGF assays.…”

Section: Introductionmentioning

confidence: 99%

Elecsys^® and Kryptor immunoassays for the measurement of sFlt-1 and PlGF to aid preeclampsia diagnosis: are they comparable?

Stepan

Hund

Dilba

et al. 2019

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background For pregnant women with suspected preeclampsia, the soluble fms-like tyrosine-kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio is a biomarker to aid diagnosis. We performed method comparisons between Elecsys® and Kryptor sFlt-1 and PlGF immunoassays and assessed the diagnostic performance for preeclampsia. Methods Serum samples from a case-control study involving 113 pregnant women with preeclampsia/elevated liver enzymes and low platelet count (HELLP) and 270 controls were analyzed. sFlt-1 and PlGF were measured using Roche Elecsys® and BRAHMS Kryptor sFlt-1/PlGF immunoassays. The sFlt-1/PlGF ratios were calculated, and Passing-Bablok regression/Bland-Altman plots were performed. Gestation-specific cut-offs, ≤33 and ≥85/≥110, were assessed. Results Mean (±2 standard deviation [SD]) differences between the Elecsys® and Kryptor values were: sFlt-1, 173.13 pg/mL (6237.66, −5891.40); PlGF, −102.71 pg/mL (186.06, −391.48); and sFlt-1/PlGF, 151.74 (1085.11, −781.63). The Elecsys® and Kryptor immunoassays showed high correlation: Pearson’s correlation coefficients were 0.913 (sFlt-1) and 0.945 (PlGF). Slopes were 1.06 (sFlt-1) and 0.79 (PlGF), resulting in ~20% lower values for Kryptor PlGF. Sensitivities and specificities using the sFlt-1/PlGF ≥85 cut-off for early-onset preeclampsia (20 + 0 to 33 + 6 weeks) were 88.1%/100.0% (Elecsys®) and 90.5%/96.2% (Kryptor), respectively, and using the ≥110 cut-off for late-onset preeclampsia (≥34 + 0 weeks) were 51.3%/96.5% (Elecsys®) and 78.9%/90.1% (Kryptor), respectively. Using Elecsys® and Kryptor sFlt-1/PlGF, 0% and 3.8% of women, respectively, were falsely ruled-in for early-onset, and 3.5% and 9.9%, respectively, for late-onset preeclampsia. Conclusions Despite high correlation between the Elecsys® and Kryptor immunoassays, we observed significant differences between sFlt-1/PlGF and PlGF results. Therefore, sFlt-1/PlGF cut-offs validated for Elecsys® immunoassays are not transferable to Kryptor immunoassays.

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Angiogenic factors: potential to change clinical practice in pre‐eclampsia?

Cited by 61 publications

References 91 publications

The performance of pre-delivery serum concentrations of angiogenic factors in predicting postpartum antihypertensive drug therapy following abdominal delivery in severe preeclampsia and normotensive pregnancy

The performance of pre-delivery serum concentrations of angiogenic factors in predicting postpartum antihypertensive drug therapy following abdominal delivery in severe preeclampsia and normotensive pregnancy

From first‐trimester screening to risk stratification of evolving pre‐eclampsia in second and third trimesters of pregnancy: comprehensive approach

Elecsys^® and Kryptor immunoassays for the measurement of sFlt-1 and PlGF to aid preeclampsia diagnosis: are they comparable?

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Angiogenic factors: potential to change clinical practice in pre‐eclampsia?

Cited by 61 publications

References 91 publications

The performance of pre-delivery serum concentrations of angiogenic factors in predicting postpartum antihypertensive drug therapy following abdominal delivery in severe preeclampsia and normotensive pregnancy

The performance of pre-delivery serum concentrations of angiogenic factors in predicting postpartum antihypertensive drug therapy following abdominal delivery in severe preeclampsia and normotensive pregnancy

From first‐trimester screening to risk stratification of evolving pre‐eclampsia in second and third trimesters of pregnancy: comprehensive approach

Elecsys® and Kryptor immunoassays for the measurement of sFlt-1 and PlGF to aid preeclampsia diagnosis: are they comparable?

Contact Info

Product

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Elecsys^® and Kryptor immunoassays for the measurement of sFlt-1 and PlGF to aid preeclampsia diagnosis: are they comparable?