Background
In the weeks preceding the clinical onset of preeclampsia, the maternal serum level
of the angiogenic placental growth factor is decreased and that of the antiangiogenic
factor soluble fms-like tyrosine kinase-1 is increased. Women presenting at specialist
clinics with signs or symptoms of hypertensive disorders have been stratified according
to concentrations of placental growth factor or the ratio of concentrations of soluble
fms-like tyrosine kinase-1 and placental growth factor to determine clinical management
for the subsequent 1-4 weeks. An alternative approach for the prediction of preeclampsia
is use of the competing risks model, a Bayes’ theorem based method, to derive patient-specific
risk for preeclampsia by various combinations of maternal characteristics and medical
history with multiples of the median values of biomarkers.
Objective
The purpose of this study was to compare the performance of screening for delivery
with preeclampsia at ≤2 and ≤4 weeks after assessment at 35+0–36+6 weeks gestation between the use of percentile cut-offs in placental growth factor
alone or the soluble fms-like tyrosine kinase-1/placental growth factor ratio and
the competing risks model.
Study Design
This was a prospective observational study in women who attended a routine hospital
visit at 35+0–36+6 weeks gestation in 2 maternity hospitals in England. The visits included the recording
of maternal demographic characteristics and medical history and the measurement of
serum placental growth factor and soluble fms-like tyrosine kinase-1 and mean arterial
pressure. The areas under the receiver operating characteristics curves were used
to compare the predictive performance for preeclampsia with delivery at ≤2 and ≤4
weeks from assessment of screening by placental growth factor alone and the soluble
fms-like tyrosine kinase-1/placental growth factor ratio with that of a previously
developed competing risks model with a combination of maternal factors, placental
growth factor, soluble fms-like tyrosine kinase-1, and mean arterial pressure (triple
test).
Results
First, the study population of 15,247 pregnancies included 326 pregnancies (2.1%)
that subsequently experienced preeclampsia. Second, in the screening for delivery
with preeclampsia at ≤2 and ≤4 weeks from assessment, the performance of the triple
test was superior to that of placental growth factor alone or the soluble fms-like
tyrosine kinase-1/placental growth factor ratio. The area under the receiver operating
characteristics curves for preeclampsia at ≤2 weeks in screening by the triple test
(0.975; 95% confidence interval, 0.964–0.985) was higher than that of placental growth
factor alone (0.900; 95% confidence interval, 0.866–0.935; P<.0001) and the soluble fms-like tyrosine kinase-1/placental growth factor ratio (0.932;
95% confidence interval, 0.904–0.960; P=.0001). Similarly, the areas under the receiver operating characteristics curves
for preeclampsia at ≤4 weeks in screening by the triple test (0.907; 95% confidence
interval, 0.886–0.928) was higher than that of placental growth factor alone (0.827;
95% confidence interval, 0.800–0.854; P<.0001) or the soluble fms-like tyrosine kinase-1/placental growth factor ratio (0.857;
95% confidence interval, 0.830–0.883; P<.0001). Third, at most, screen-positive rates of 2–30% the detection rate of delivery
with preeclampsia at ≤2 and ≤4 weeks that was achieved by the triple test was approximately
10% higher than that of the soluble fms-like tyrosine kinase-1/placental growth factor
ratio and 20% higher than that of placental growth factor alone; the negative predictive
value was similar for the 3 tests.
Conclusion
At 35+0–36+6 weeks gestation, the performance of screening for imminent delivery with preeclampsia
by the competing risks model is superior to that of placental growth factor alone
or the soluble fms-like tyrosine kinase-1/placental growth factor ratio.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to American Journal of Obstetrics & GynecologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Excess placental soluble fms-like tyrosine kinase 1 (sFlt-11) may contribute to endothelial dysfunction, hypertension, and proteinuria in pre-eclampsia.J Clin Invest. 2003; 111: 649-658
- Circulating angiogenic factors and the risk of pre-eclampsia.N Engl J Med. 2004; 350: 672-683
- Maternal plasma concentrations of angiogenic/anti-angiogenic factors are of prognostic value in patients presenting to the obstetrical triage area with the suspicion of pre-eclampsia.J Matern Fetal Neonatal Med. 2011; 24: 1187-1207
- Angiogenic factors as diagnostic tests for preeclampsia: a performance comparison between two commercial immunoassays.Am J Obstet Gynecol. 2011; 205: 469.e1-469.e8
- The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients.Am J Obstet Gynecol. 2012; 206: 58.e1-58.e8
- Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study.Circulation. 2013; 128: 2121-2131
- Maternal plasma concentrations of angiogenic/antiangiogenic factors in the third trimester of pregnancy to identify the patient at risk for stillbirth at or near term and severe late preeclampsia.Am J Obstet Gynecol. 2013; 208: 287.e1-287.e15
- Competing risks model in screening for preeclampsia by serum placental growth factor and soluble fms-like tyrosine kinase-1 at 30-33 weeks gestation.Fetal Diagn Ther. 2014; 35: 240-248
- Predictive value of the sFlt-1:PlGF ratio in women with suspected pre-eclampsia.N Engl J Med. 2016; 374: 13-22
- A comparison of the diagnostic utility of the sFlt-1/PlGF ratio versus PlGF alone for the detection of preeclampsia/HELLP syndrome.Hypertens Pregnancy. 2016; 35: 295-305
- Development of pre-eclampsia within 4 weeks of sFlt-1/PlGF ratio > 38: comparison of performance at 31-34 vs 35-37 weeks gestation.Ultrasound Obstet Gynecol. 2017; 49: 209-212
- Competing risks model in screening for preeclampsia by maternal characteristics and medical history.Am J Obstet Gynecol. 2015; 213: 62.e1-62.e10
- Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks gestation.Am J Obstet Gynecol. 2016; 214: 103.e1-103.e12
- Predictive performance of the competing risk model in screening for preeclampsia.Am J Obstet Gynecol. 2019; 220: 199.e1-199.e13
- Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 19–24 weeks gestation.Am J Obstet Gynecol. 2016; 214: 619.e1-619.e17
- Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 30–34 weeks gestation.Am J Obstet Gynecol. 2016; 215: 87.e1-87.e17
- Competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 35–37 weeks gestation.Ultrasound Obstet Gynecol. 2016; 48: 72-79
- Proposed clinical management of pregnancies after combined screening for preeclampsia at 35–37 weeks gestation.Ultrasound Obstet Gynecol. 2017; 50: 383-387
- Screening for pre-eclampsia at 35-37 weeks gestation.Ultrasound Obstet Gynecol. 2018; 52: 501-506
- Comparison of screening for pre-eclampsia at 31-34 weeks gestation by sFlt-1/PlGF ratio and a method combining maternal factors with sFlt-1 and PlGF.Ultrasound Obstet Gynecol. 2017; 49: 201-208
- Protocol for measurement of mean arterial pressure at 11-13 weeks gestation.Fetal Diagn Ther. 2012; 31: 42-48
- A critical evaluation of sonar crown rump length measurements.BJOG. 1975; 82: 702-710
- Fetal biometry at 14–40 weeks gestation.Ultrasound Obstet Gynecol. 1994; 4: 34-38
- The classification and diagnosis of the hypertensive disorders of pregnancy: Statement from the international society for the study of hypertension in pregnancy (ISSHP).Hypertens Pregnancy. 2001; 20 (IX–XIV)
- American College of Obstetricians and Gynecologists and the Task Force on Hypertension in Pregnancy. Hypertension in pregnancy.Obstet Gynecol. 2013; 122: 1122-1131
- R. A language and environment for statistical computing.R Foundation for Statistical Computing, Vienna, Austria2011 (ISBN 3-900051-07-0. Available at:) (Accessed December 20, 2018)
- pROC: an open-source package for R and S+ to analyze and compare ROC curves.BMC Bioinformatics. 2011; 12: 77-84
- Maternal serum placental growth factor at 12, 22, 32 and 36 weeks gestation in screening for pre-eclampsia.Ultrasound Obstet Gynecol. 2016; 47: 472-477
- Maternal serum soluble fms-like tyrosine kinase-1 at 12, 22, 32 and 36 weeks gestation in screening for pre-eclampsia.Ultrasound Obstet Gynecol. 2016; 47: 478-483
- Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia.N Engl J Med. 2017; 377: 613-622
- Aspirin for Evidence-Based Preeclampsia Prevention trial: influence of compliance on beneficial effect of aspirin in prevention of preterm preeclampsia.Am J Obstet Gynecol. 2017; 217: 685.e1-685.e5
- Aspirin for Evidence-Based Preeclampsia Prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history.Am J Obstet Gynecol. 2017; 217: 585.e1-585.e5
- Aspirin for the prevention of preterm and term preeclampsia: systematic review and metaanalysis.Am J Obstet Gynecol. 2018; 218: 287-293.e1
- Screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks gestation.Ultrasound Obstet Gynecol. 2018; 52: 186-195
Article info
Publication history
Published online: February 07, 2019
Accepted:
January 30,
2019
Received in revised form:
January 22,
2019
Received:
December 22,
2018
Footnotes
Supported by a grant from the Fetal Medicine Foundation (Charity No: 1037116). The reagents and equipment for the measurement of serum placental growth factor and soluble fms-like tyrosine kinase-1 were provided by Thermo Fisher Scientific.
These bodies had no involvement in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
The authors report no conflict of interest.
Cite this article as: Ciobanu A, Wright A, Panaitescu A, et al. Prediction of imminent preeclampsia at 35–37 weeks gestation. Am J Obstet Gynecol 2019;220:584.e1-11.
Identification
Copyright
© 2019 Elsevier Inc. All rights reserved.
