OBSTETRICS
Angiogenic factors as diagnostic tests for preeclampsia:
a performance comparison between
two commercial immunoassays
Samantha J. Benton, BSc; Yuxiang Hu, MD; Fang Xie, MD, PhD; Kenneth Kupfer, PhD;
Seok-Won Lee, PhD; Laura A. Magee, MD, MSc; Peter von Dadelszen, MBChB, DPhil
OBJECTIVE: Placental growth factor and soluble Fms-like tyrosine ki-
nase-1 may be potential diagnostic markers of preeclampsia. We com-
pared performances of 2 immunoassays, the Triage placental growth
factor assay and the Elecsys soluble Fms-like tyrosine kinase-1/placen-
tal growth factor ratio in diagnosing preeclampsia.
STUDY DESIGN: A single site, case-control study of 44 patients with
preeclampsia and 84 matched normal pregnant controls. Samples
were collected at the time of diagnosis. Assays were performed accord-
ing to product inserts.
RESULTS: Both assays had optimal performance in diagnosing early-
onset preeclampsia with area under the receiver operating characteris-
tic curves of 0.99 (Triage: 100% sensitivity, 96% specificity; Elecsys:
64% sensitivity, 100% specificity for early-onset preeclampsia). Reas-
signment of the Elecsys cutoff for a positive test based on receiver op-
erating characteristic curves increased sensitivity to 92%.
CONCLUSION: Using product insert cutoffs, Triage appears to have
greater sensitivity at only a small reduction in specificity compared with
Elecsys in the diagnosis of early-onset preeclampsia. A different cutoff
may improve Elecsys sensitivity.
Key words: angiogenesis, biomarker, diagnostic test, placental
growth factor (PlGF), preeclampsia, soluble Fms-like tyrosine kinase-1
(sFlt-1)
Cite this article as: Benton SJ, Hu Y, Xie F, et al. Angiogenic factors as diagnostic tests for preeclampsia: a performance comparison between two commercial
immunoassays. Am J Obstet Gynecol 2011;205:469.e1-8.
P
reeclampsia is a leading cause of ma-
ternal and perinatal mortality and
morbidity.
1
Affecting 2-5% of pregnan-
cies, it is usually characterized by hyper-
tension (140/90 mm Hg) and protein-
uria (300 mg/d) after 20
+0
weeks of
gestation. However, preeclampsia is a
heterogeneous syndrome and clinical
presentation can be highly variable and
may not include hypertension and pro-
teinuria.
1-4
The British Eclampsia Survey
Team (BEST) found that only 57% of
women with eclampsia had documented
hypertension with proteinuria within the
week before the first seizure.
5
Women with
nonproteinuric, preexisting, or gestational
hypertension can evolve into preeclamp-
sia and have been found to have worse
outcomes than their classically defined
preeclampsia counterparts.
6
From the
Preeclampsia Integrated Estimate of
RiSk (PIERS) Study dataset,
3
254 of 2024
women with preeclampsia did not fulfill
the research definition of preeclampsia
on the day of their hospital admission.
Likewise, of the 106 women who had an
adverse maternal outcome within 48
hours of hospital admission, 21 (20%)
had isolated HELLP (hemolysis, elevated
liver enzymes, low platelets) syndrome
and 6 (5%) had hyperuricemic hyper-
tension (unpublished data). Mimickers
of preeclampsia (eg, renal disease with
preexisting hypertension and/or protein-
uria) can also lead to clinical uncertainty.
7
Women with nonclassically defined pre-
eclampsia are still at risk for adverse out-
comes and represent a clinically challeng-
ing subset of women to diagnose.
More comprehensive diagnostic tools
are needed to aid in identifying women
with atypical preeclampsia in clinical
From the Departments of Obstetrics and Gynaecology, Faulty of Medicine (Ms Benton and
Drs Hu, Xie, Magee, and von Dadelszen) and Medicine, Faculty of Medicine (Dr Magee), and
the Child and Family Research Institute (Ms Benton and Drs Hu, Xie, Magee, and von
Dadelszen), University of British Columbia, Vancouver, British Columbia, Canada; and Alere
San Diego (Drs Kupfer and Lee), San Diego, CA.
Received Jan. 10, 2011; revised March 10, 2011; accepted June 15, 2011.
This study was funded by a New Investigator Pilot Project Grant from the Canadian Institutes of
Health Research (CIHR) Institute of Infection and Immunity (P.v.D.) and funded in part by Alere
International; F.X. is the recipient of a studentship from the CIHR-funded Interdisciplinary Training
Program in Women’s Reproductive Health, Child and Family Research Institute. L.A.M., and
P.v.D. are the recipients of salary awards from the Michael Smith Foundation for Health Research
(L.A.M., P.v.D.), CIHR (P.v.D.), and the Child and Family Research Institute (P.v.D.).
P.v.D. and L.A.M. have received fees for opinions in legal cases related to preeclampsia. P.v.D. is
a principal investigator for an investigator-initiated safety and efficacy trial of a possible disease-
modifying therapy for preeclampsia sponsored by Eli Lilly, Canada, and is a site investigator for a
preeclampsia prediction/diagnosis study sponsored by Alere International. L.A.M. is a
coinvestigator on both studies. P.v.D. is also a consultant for Alere International. K.K. is an
employee of Alere San Diego. S.W.L. is a former employee of Alere San Diego.
Reprints: Peter von Dadelszen, MBChB, DPhil, 2H30-4500 Oak St., Vancouver, BC V6H 3N1,
Canada. pvd@cw.bc.ca
0002-9378/$36.00 • © 2011 Mosby, Inc. All rights reserved. • doi: 10.1016/j.ajog.2011.06.058
Research www. AJOG.org
NOVEMBER 2011 American Journal of Obstetrics & Gynecology 469.e1