Prediction of hypertensive disorders after screening at 36 weeks' gestation: comparison of angiogenic markers with competing‐risks model

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ObjectiveTo examine the performance of screening for preterm‐ and term‐preeclampsia (PE) at 11‐13 weeks' gestation by maternal factors and combinations of maternal serum glycosylated fibronectin (GlyFn), mean arterial pressure (MAP), uterine artery pulsatility index (UtA‐PI) and serum placental growth factor (PlGF).MethodsThis was a case‐control study in which maternal serum GlyFn was measured in stored samples from a non‐intervention screening study in singleton pregnancies at 11+0 – 13+6 weeks' gestation using a point‐of‐care device. In the same samples PlGF was measured by time‐resolved fluorometry. We used samples from women who delivered with PE at <37 weeks' gestation (n=100), PE at ≥37 weeks (n=100), gestational hypertension (GH) at <37 weeks (n=100), GH at ≥37 weeks (n=100), and 1,000 normotensive controls with no pregnancy complications. In all cases MAP and UtA‐PI had been measured during the routine 11+0 – 13+6 weeks visit of the women. Levels of GlyFn were transformed to multiple of the expected median value (MoM) after adjusting for maternal demographic characteristics and elements from the medical history. Similarly, the measured values of MAP, UtA‐PI and PlGF were converted to MoMs. The competing risks model was used to combine the prior distribution of the gestational age at delivery with PE, obtained from maternal characteristics, with various combinations of biomarker MoM values to derive the patient‐specific risks of delivery with PE or GH at <37 and ≥37 weeks' gestation. The performance of screening was estimated by examining the area under the receiver operating characteristic curve (AUC) and detection rate (DR) at 10% fixed false‐positive rate (FPR).ResultsThe variables from maternal characteristics and medical history with significant contribution to the measurement of GlyFn were maternal age, weight, height, race, smoking and previous history of PE. In pregnancies that developed PE, GlyFn MoM was increased and the deviation from normal decreased with increasing gestational age at delivery. The DR and AUC for delivery with PE at <37 weeks' gestation in screening by maternal factors alone were 50% and 0.834, respectively, and these increased to 80% and 0.949, respectively, when maternal risk factors were combined with MAP, UtA‐PI and PlGF (triple test). The performance of the triple test was similar to that of screening by a combination of maternal factors with MAP, UtA‐PI and GlyFn (DR 79% and AUC 0.946) and in screening by a combination of maternal factors with MAP, PlGF and GlyFn (DR 81% and AUC 0.932). The performance of screening for delivery with PE at ≥37 weeks'gestation was poor with DRs of 35% in screening with maternal factors alone, increasing to only 39% with use of the triple test; Similar results were obtained when GlyFn replaced PlGF or UtA‐PI in the triple test. The DRs, at 10% FPR, of GH with delivery at <37 and ≥37 weeks'gestation in screening by maternal factors alone were 34% and 25%, respectively, and these increased to 54% and 31%, respectively in screening by the triple test; similar results were obtained when GlyFn replaced PlGF or UtA‐PI in the triple test.ConclusionGlyFn is a potentially useful biomarker in first trimester screening for preterm‐PE, but the results of this case‐control study need to be validated by prospective screening studies. The performance of screening for term PE or GH at 11+0 to 13+6 weeks by any combination of biomarkers is poor.This article is protected by copyright. All rights reserved.

Section: Implications For Clinical Practicementioning

confidence: 99%

Screening for pre‐eclampsia by maternal serum glycosylated fibronectin at 11−13 weeks' gestation

Sokratous,

Bednorz,

Sarli

et al. 2023

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“…In a recent study, we suggested that GlyFn is a potentially useful first‐trimester biomarker for preterm PE 21 . We have also reported that prediction of term PE is achieved by screening at 35–37 weeks' gestation by a combination of maternal risk factors with MAP, PlGF and sFlt‐1, with a detection rate for term PE of about 70% at a screen‐positive rate of 10% 22–24 .…”

Section: Discussionmentioning

confidence: 95%

“…We have demonstrated previously the value of screening for preterm PE at 11-13 weeks' gestation and screening for term PE at 35-37 weeks with use of the competing-risks approach; essentially, information from maternal demographic characteristics and medical history are combined with multiples of the median values of biomarkers, adjusted for maternal factors, to provide accurate and reproducible personalized assessment of risks [19][20][21][22][23][24][25][26] . We have also advocated that the same approach be used in the prediction of imminent PE in women presenting to specialist clinics with some signs and/or symptoms of hypertensive disorder [24][25][26] . We suggested that use of cut-offs in measured biomarkers or their ratio to define clinical management has the advantage of simplicity.…”

Section: Interpretation Of Results and Implications For Clinical Prac...mentioning

confidence: 99%

Prediction using serum glycosylated fibronectin of imminent pre‐eclampsia in women with new‐onset hypertension

Sokratous,

Bednorz,

Wright

et al. 2023

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ObjectiveTo compare the predictive performance for delivery with pre‐eclampsia (PE) within 2 weeks after assessment in women with new‐onset hypertension at 24–41 weeks' gestation between serum glycosylated fibronectin (GlyFn) concentration, serum placental growth factor (PlGF) concentration and soluble fms‐like tyrosine kinase‐1 (sFlt‐1) to PlGF concentration ratio.MethodsThis was a prospective observational study of 409 women with a singleton pregnancy presenting at 24–41 weeks' gestation with new‐onset hypertension. The recommended cut‐off for sFlt‐1/PlGF ratio for the prediction of PE in the platform used in this study is 85; the appropriate cut‐offs for GlyFn and PlGF were determined to achieve the same screen‐positive rate as that of sFlt‐1/PlGF ratio > 85. We then compared the predictive performance for delivery with PE within 2 weeks after presentation between GlyFn, PlGF and sFlt‐1/PlGF, both overall and in subgroups according to gestational age at presentation.ResultsDelivery with PE within 2 weeks occurred in 93 (22.7%) cases. The screen‐positive rate for sFlt‐1/PlGF ratio > 85 was 46.2%. The cut‐off corresponding to a screen‐positive rate of 46.2% was 75 pg/mL for PlGF and 510 µg/mL for GlyFn. The overall detection rate for delivery with PE within 2 weeks after presentation was 62.4% (95% CI, 51.7–72.2%) for GlyFn and sFlt‐1/PlGF and 60.2% (95% CI, 49.5–70.2%) for PlGF. In all women who delivered with PE within 2 weeks after presentation at < 34 weeks' gestation and in about 60–70% of those presenting at < 38 weeks, GlyFn and sFlt‐1/PlGF were increased and PlGF was reduced. However, the screen‐positive rate for these tests was very high at about 45%. The predictive performance for delivery with PE within 2 weeks after presentation at ≥ 38 weeks' gestation was poorer for all three methods of screening, with detection rates of 47–63% at screen‐positive rates of 40–50%.ConclusionsIn women with new‐onset hypertension, the predictive performance for delivery with PE within 2 weeks after presentation for serum GlyFn is similar to that of PlGF and the sFlt‐1/PlGF ratio, but GlyFn may be the preferred option because it is a rapid point‐of‐care test. However, the predictive performance for all tests is relatively poor. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

“…Treatment of the high-risk group with aspirin (150 mg/day from 12 to 36 weeks) reduces the rates of early and preterm PE by about 90% and 60%, respectively 5 . The second strategy involves assessment of risk at 36 weeks' gestation by a combination of maternal risk factors with MAP, PlGF and soluble fms-like tyrosine kinase-1 (sFlt-1) (third-trimester triple test), and has a detection rate for term PE with delivery at ≥ 37 weeks of about 70%, at a screen-positive rate of 10% [6][7][8] . A randomized trial is currently evaluating timed birth based on personalized risk of PE, a strategy that has the potential to decrease the rate of term PE by about 60% 9 .…”

Section: Introductionmentioning

confidence: 99%

Prediction using serum glycosylated fibronectin and angiogenic factors of superimposed pre‐eclampsia in women with chronic hypertension

Sokratous,

Bednorz,

Syngelaki

et al. 2023

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ObjectiveTo compare the predictive performance for delivery with preeclampsia (PE) within 2 weeks of assessment in women with chronic hypertension at 24‐41 weeks’ gestation between serum glycosylated fibronectin (GlyFn) concentration, serum placental growth factor (PlGF) concentration and soluble fms‐like tyrosine kinase‐1 (sFLT‐1) / PlGF concentration ratio.MethodsThis was a prospective study in 104 women with singleton pregnancies and chronic hypertension presenting at 24‐41 weeks’ gestation. In 26 (25.0%) cases there was superimposed PE within 2 weeks from sampling. We compared the predictive performance for superimposed PE between GlyFn, PlGF and sFLT‐1 / PlGF at fixed screen positive rates of approximately 10%.ResultsThe median gestational age at sampling was 34.1 (31.5, 35.6) weeks and in 84.6% (88/104) of cases it was <36 weeks. The predictive performance for superimposed PE of the three methods of screening was similar with detection rates of about 23‐27%, at screen positive rate of 11% and false positive rate of about 5%.ConclusionGlyFn is a simple point‐of‐care test without the need of a laboratory and can provide results within 10 minutes of testing. In this respect it may potentially replace the angiogenic markers that are currently used in the prediction of imminent PE in high‐risk women. However, neither GlyFn nor angiogenic factors are likely to improve the management of women with chronic hypertension, because their predictive performance for superimposed PE is poor.This article is protected by copyright. All rights reserved.