Rule-in and rule-out of pre-eclampsia using DELFIA Xpress PlGF 1-2-3 and sFlt-1: PlGF ratio

Laura Bremner; Carolyn Gill; Paul T. Seed; Frances Conti-Ramsden; Louise Webster; Jessica Fleminger; Lucy C. Chappell; Andrew Shennan; Kate Bramham

doi:10.1016/j.preghy.2021.12.008

Rule-in and rule-out of pre-eclampsia using DELFIA Xpress PlGF 1-2-3 and sFlt-1: PlGF ratio

Laura Bremner, Carolyn Gill, Paul T. Seed, Frances Conti-Ramsden, Louise Webster, Jessica Fleminger, Lucy C. Chappell, Andrew Shennan, Kate Bramham^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

Objectives: The objective of this study was to explore and validate thresholds for Placental growth factor (PlGF) and soluble fms-like tyrosine-kinase 1 (s-Flt-1) (as s-Flt-1: PlGF ratio), to rule-in and rule-out disease in women with suspected pre-eclampsia, using DELFIA® Xpress PlGF1-2-3 and sFlt-1 assays. Study Design: 369 samples from women with suspected or confirmed pre-eclampsia were analysed from a prospective cohort study. Main Outcome Measures: Serum PlGF and sFlt-1: PlGF were quantified using DELFIA® Xpress PlGF1-2-3 and DELFIA® Xpress sFlt-1 tests. Performances were evaluated at established and exploratory thresholds. Low PlGF concentration and sFlt-1: PlGF AUROC were compared. Results: PlGF 1-2-3 concentration thresholds were confirmed to have high performance for rule-in (<50 pg/ml) and rule-out (≥150 pg/ml) pre-eclampsia within seven days (20–33⁺⁶ Weeks <50 pg/ml: Negative predictive value (NPV) 90.7% (95% CI 83.9, 95.3); ≥150 pg/ml: NPV 94.8% (95% CI 88.4, 98.3)) and 28 days (20–33⁺⁶ Weeks <50 pg/ml: Negative predictive value (NPV) 83.9% (95% CI 76.0, 90.0); ≥150 pg/ml: NPV 92.8% (95% CI 85.7, 97.0)). Optimal sFlt-1: PlGF thresholds for rule-in were ≥ 70 before 34 weeks and ≥ 90 after 34 weeks, and <50 to rule-out pre-eclampsia. Low PlGF alone had comparable performance to sFlt-1: PlGF, but test performance for both was reduced in women with Kidney Disease. Conclusions: DELFIA® Xpress PlGF1-2-3 and sFlt-1 assays for pre-eclampsia rule-in and rule-out have comparable performance to other established assays, and could be an alternative for clinical use. Performance was not enhanced by use of sFlt-1: PlGF ratio, suggesting that PlGF alone could provide a cheaper alternative to dual biomarker testing.

Original language	English
Pages (from-to)	96-102
Number of pages	7
Journal	Pregnancy Hypertension
Volume	27
Early online date	23 Dec 2021
DOIs	https://doi.org/10.1016/j.preghy.2021.12.008
Publication status	Published - Mar 2022

Keywords

Placental growth factor
Pre-eclampsia
Predictive test
Soluble fms-like tyrosine kinase-1

Access to Document

10.1016/j.preghy.2021.12.008

Cite this

@article{8dfc9eb20b77418393796a706b9ed4d6,

title = "Rule-in and rule-out of pre-eclampsia using DELFIA Xpress PlGF 1-2-3 and sFlt-1: PlGF ratio",

abstract = "Objectives: The objective of this study was to explore and validate thresholds for Placental growth factor (PlGF) and soluble fms-like tyrosine-kinase 1 (s-Flt-1) (as s-Flt-1: PlGF ratio), to rule-in and rule-out disease in women with suspected pre-eclampsia, using DELFIA{\textregistered} Xpress PlGF1-2-3 and sFlt-1 assays. Study Design: 369 samples from women with suspected or confirmed pre-eclampsia were analysed from a prospective cohort study. Main Outcome Measures: Serum PlGF and sFlt-1: PlGF were quantified using DELFIA{\textregistered} Xpress PlGF1-2-3 and DELFIA{\textregistered} Xpress sFlt-1 tests. Performances were evaluated at established and exploratory thresholds. Low PlGF concentration and sFlt-1: PlGF AUROC were compared. Results: PlGF 1-2-3 concentration thresholds were confirmed to have high performance for rule-in (<50 pg/ml) and rule-out (≥150 pg/ml) pre-eclampsia within seven days (20–33+6 Weeks <50 pg/ml: Negative predictive value (NPV) 90.7% (95% CI 83.9, 95.3); ≥150 pg/ml: NPV 94.8% (95% CI 88.4, 98.3)) and 28 days (20–33+6 Weeks <50 pg/ml: Negative predictive value (NPV) 83.9% (95% CI 76.0, 90.0); ≥150 pg/ml: NPV 92.8% (95% CI 85.7, 97.0)). Optimal sFlt-1: PlGF thresholds for rule-in were ≥ 70 before 34 weeks and ≥ 90 after 34 weeks, and <50 to rule-out pre-eclampsia. Low PlGF alone had comparable performance to sFlt-1: PlGF, but test performance for both was reduced in women with Kidney Disease. Conclusions: DELFIA{\textregistered} Xpress PlGF1-2-3 and sFlt-1 assays for pre-eclampsia rule-in and rule-out have comparable performance to other established assays, and could be an alternative for clinical use. Performance was not enhanced by use of sFlt-1: PlGF ratio, suggesting that PlGF alone could provide a cheaper alternative to dual biomarker testing.",

keywords = "Placental growth factor, Pre-eclampsia, Predictive test, Soluble fms-like tyrosine kinase-1",

author = "Laura Bremner and Carolyn Gill and Seed, {Paul T.} and Frances Conti-Ramsden and Louise Webster and Jessica Fleminger and Chappell, {Lucy C.} and Andrew Shennan and Kate Bramham",

note = "Funding Information: This study was funded by a project grant from Perkin Elmer. This was an investigator led-study; the funder had no role in study design, patient recruitment, data collection, analysis or interpretation, nor in the writing of the manuscript or decision to submit for publication. Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2022",

month = mar,

doi = "10.1016/j.preghy.2021.12.008",

language = "English",

volume = "27",

pages = "96--102",

journal = "Pregnancy Hypertension",

issn = "2210-7789",

publisher = "Elsevier BV",

}

TY - JOUR

T1 - Rule-in and rule-out of pre-eclampsia using DELFIA Xpress PlGF 1-2-3 and sFlt-1

T2 - PlGF ratio

AU - Bremner, Laura

AU - Gill, Carolyn

AU - Seed, Paul T.

AU - Conti-Ramsden, Frances

AU - Webster, Louise

AU - Fleminger, Jessica

AU - Chappell, Lucy C.

AU - Shennan, Andrew

AU - Bramham, Kate

N1 - Funding Information: This study was funded by a project grant from Perkin Elmer. This was an investigator led-study; the funder had no role in study design, patient recruitment, data collection, analysis or interpretation, nor in the writing of the manuscript or decision to submit for publication. Publisher Copyright: © 2021 The Authors

PY - 2022/3

Y1 - 2022/3

N2 - Objectives: The objective of this study was to explore and validate thresholds for Placental growth factor (PlGF) and soluble fms-like tyrosine-kinase 1 (s-Flt-1) (as s-Flt-1: PlGF ratio), to rule-in and rule-out disease in women with suspected pre-eclampsia, using DELFIA® Xpress PlGF1-2-3 and sFlt-1 assays. Study Design: 369 samples from women with suspected or confirmed pre-eclampsia were analysed from a prospective cohort study. Main Outcome Measures: Serum PlGF and sFlt-1: PlGF were quantified using DELFIA® Xpress PlGF1-2-3 and DELFIA® Xpress sFlt-1 tests. Performances were evaluated at established and exploratory thresholds. Low PlGF concentration and sFlt-1: PlGF AUROC were compared. Results: PlGF 1-2-3 concentration thresholds were confirmed to have high performance for rule-in (<50 pg/ml) and rule-out (≥150 pg/ml) pre-eclampsia within seven days (20–33+6 Weeks <50 pg/ml: Negative predictive value (NPV) 90.7% (95% CI 83.9, 95.3); ≥150 pg/ml: NPV 94.8% (95% CI 88.4, 98.3)) and 28 days (20–33+6 Weeks <50 pg/ml: Negative predictive value (NPV) 83.9% (95% CI 76.0, 90.0); ≥150 pg/ml: NPV 92.8% (95% CI 85.7, 97.0)). Optimal sFlt-1: PlGF thresholds for rule-in were ≥ 70 before 34 weeks and ≥ 90 after 34 weeks, and <50 to rule-out pre-eclampsia. Low PlGF alone had comparable performance to sFlt-1: PlGF, but test performance for both was reduced in women with Kidney Disease. Conclusions: DELFIA® Xpress PlGF1-2-3 and sFlt-1 assays for pre-eclampsia rule-in and rule-out have comparable performance to other established assays, and could be an alternative for clinical use. Performance was not enhanced by use of sFlt-1: PlGF ratio, suggesting that PlGF alone could provide a cheaper alternative to dual biomarker testing.

AB - Objectives: The objective of this study was to explore and validate thresholds for Placental growth factor (PlGF) and soluble fms-like tyrosine-kinase 1 (s-Flt-1) (as s-Flt-1: PlGF ratio), to rule-in and rule-out disease in women with suspected pre-eclampsia, using DELFIA® Xpress PlGF1-2-3 and sFlt-1 assays. Study Design: 369 samples from women with suspected or confirmed pre-eclampsia were analysed from a prospective cohort study. Main Outcome Measures: Serum PlGF and sFlt-1: PlGF were quantified using DELFIA® Xpress PlGF1-2-3 and DELFIA® Xpress sFlt-1 tests. Performances were evaluated at established and exploratory thresholds. Low PlGF concentration and sFlt-1: PlGF AUROC were compared. Results: PlGF 1-2-3 concentration thresholds were confirmed to have high performance for rule-in (<50 pg/ml) and rule-out (≥150 pg/ml) pre-eclampsia within seven days (20–33+6 Weeks <50 pg/ml: Negative predictive value (NPV) 90.7% (95% CI 83.9, 95.3); ≥150 pg/ml: NPV 94.8% (95% CI 88.4, 98.3)) and 28 days (20–33+6 Weeks <50 pg/ml: Negative predictive value (NPV) 83.9% (95% CI 76.0, 90.0); ≥150 pg/ml: NPV 92.8% (95% CI 85.7, 97.0)). Optimal sFlt-1: PlGF thresholds for rule-in were ≥ 70 before 34 weeks and ≥ 90 after 34 weeks, and <50 to rule-out pre-eclampsia. Low PlGF alone had comparable performance to sFlt-1: PlGF, but test performance for both was reduced in women with Kidney Disease. Conclusions: DELFIA® Xpress PlGF1-2-3 and sFlt-1 assays for pre-eclampsia rule-in and rule-out have comparable performance to other established assays, and could be an alternative for clinical use. Performance was not enhanced by use of sFlt-1: PlGF ratio, suggesting that PlGF alone could provide a cheaper alternative to dual biomarker testing.

KW - Placental growth factor

KW - Pre-eclampsia

KW - Predictive test

KW - Soluble fms-like tyrosine kinase-1

UR - http://www.scopus.com/inward/record.url?scp=85121980476&partnerID=8YFLogxK

U2 - 10.1016/j.preghy.2021.12.008

DO - 10.1016/j.preghy.2021.12.008

M3 - Article

AN - SCOPUS:85121980476

SN - 2210-7789

VL - 27

SP - 96

EP - 102

JO - Pregnancy Hypertension

JF - Pregnancy Hypertension

ER -

Rule-in and rule-out of pre-eclampsia using DELFIA Xpress PlGF 1-2-3 and sFlt-1: PlGF ratio

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this