Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 30-34 weeks’ gestation
Open accessAbstract
Background Preeclampsia (PE) affects 2-3% of all pregnancies and is a major cause of maternal and perinatal morbidity and mortality. We have proposed a 2-stage strategy for the identification of pregnancies at high risk of developing PE. The objective of the first stage, at 11-13 weeks' gestation, is a reduction in the prevalence of the disease through pharmacological intervention in the high-risk group. The objective of the second stage, during the second and/or third trimesters, is to improve perinatal outcome through close monitoring of the high-risk group for earlier diagnosis of the clinical signs of the disease and selection of the appropriate, time, place, and method of delivery.Objective The objective of the study was to examine the performance of screening for PE by a combination of maternal factors with early third-trimester biomarkers.Study design This was a cohort study and data were derived from consecutive women with singleton pregnancies attending for their routine hospital visit at 30-34 weeks' gestation in 3 maternity hospitals in England between March 2011 and December 2014. In the first phase of the study, only uterine artery pulsatility index (UTPI) was measured and then measurement of mean arterial pressure (MAP) was added, and in the final phase, the serum concentration of placental growth factor (PLGF) was measured and then soluble fms-like tyrosine kinase-1 (SFLT) was added. We had data on UTPI, MAP, PLGF, and SFLT from 30,935, 29,042, 10,123, and 8,264 pregnancies, respectively. The Bayes theorem was used to combine the a priori risk from maternal factors with various combinations of biomarker multiple of the median values. Ten-fold cross-validation was used to estimate the performance of screening for PE requiring delivery at < 37 weeks' gestation (preterm-PE) and those delivering at ≥ 37 weeks (term-PE). The empirical performance was compared with model predictions.Results In pregnancies that developed PE, the values of MAP, UTPI, and SFLT were increased and PLGF was decreased. For all biomarkers the deviation from normal was greater for preterm-PE than term-PE, and therefore, the performance of screening was inversely related to the gestational age at which delivery become necessary for maternal and/or fetal indications. Combined screening by maternal factors, MAP, UTPI, PLGF, and SFLT predicted 98% (95% confidence interval, 88-100%) of preterm-PE and 49% (95% confidence interval, 42-57%) of term-PE, at a false-positive rate of 5%. These empirical detection rates are compatible with the respective model-based rates of 98% and 54%, but the latter were optimistically biased.Conclusion Combination of maternal factors and biomarkers in the early third trimester could predict nearly all cases of preterm-PE and half of those with term-PE, at 5% false-positive rate.
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There is excessive production of sVEGFR-1 and soluble endoglin in the uterus of preeclamptic patients proportional to the severity of the disease.
“There is excessive production of sVEGFR-1 and soluble endoglin in the uterus of preeclamptic patients(121) proportional to the severity of the disease (151–153)”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [153]
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- Authors
- Tsiakkas, A., Saiid, Y., Wright, A., Wright, D., & Nicolaides, K. H.
- Affiliations
- King's College London (GB)
- University of Exeter (GB)
- Corresponding author
- Nicolaides, Kypros H.
- Venue
- American Journal of Obstetrics and Gynecology
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 215
- Issue
- 1
- Pages
- 87.e1-87.e17
- ISSN
- 0002-9378 (ISSN-L)
- OpenAlex
- W3022297674
- Cited by
- 119
- References
- 40
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 9 · 2023: 7 · 2022: 9 · 2021: 17 · 2020: 9 · 2019: 13 · 2018: 12 · 2017: 19 · 2016: 10 · 2015: 1
- FWCI
- 23.21
- Type
- journal article
- Language
- en
- Open access
- green
- kclpure.kcl.ac.uk
- Licence
- Locations
- American Journal of Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Psychiatry and Mental health › Neurological Complications and Syndromes
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- preeclampsia, preeclampsia screening, competing risk model, uterine artery pulsatility index, mean arterial pressure, placental growth factor, soluble fms-like tyrosine kinase-1, maternal risk factors, preterm preeclampsia, term preeclampsia, Bayes' theorem, screening performance, singleton pregnancy
- MeSH terms
- Adult, Female, Gestational Age, Humans, Mass Screening, Pre-Eclampsia, Predictive Value of Tests, Pregnancy, Pregnancy Trimester, Third, Models, Statistical, Biomarkers, Risk Assessment, Uterine Artery
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