Abstract
Background: This study aims to evaluate the performance of the soluble Fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio to predict early-onset, preterm and severe preeclampsia at mid-pregnancy in asymptomatic women.
Methods: Based on a prospective cohort of 7929 pregnant women from the Quebec City metropolitan area, a nested case-control study was performed including 111 women who developed preeclampsia and 69 women with gestational hypertension matched with 338 normotensive women. Serum sFlt-1 and PlGF were measured between 20 and 32 weeks of gestation. The performance of the sFlt-1/PlGF ratio, expressed as raw values and multiples of the median (MoM) for the prediction of early-onset, preterm and severe preeclampsia was evaluated.
Results: Women who developed preeclampsia had significantly higher MoM sFlt-1/PlGF ratio (p<0.001). In the early-onset preeclampsia group, the median of the MoM distribution was 24.0 and the area under the receiver operating characteristic curve (AUC) was 0.977, giving sensitivities of 77.8% and 88.9% at false-positive rates of 5% and 10%. Positive predictive values (PPV) were 2.5% and 1.5%, respectively. In a subset between 26 and 32 weeks of gestation, at a threshold of 30, the sFlt-1/PlGF ratio yielded 100% specificity and identified, respectively, 85.7% and 65.2% of women who developed early-onset and preterm preeclampsia.
Conclusions: The sFlt-1/PlGF ratio has the potential to predict early-onset and preterm preeclampsia at mid-pregnancy in asymptomatic women. However, care must be paid to the prevalence of early-onset preeclampsia in the population since low prevalence reduces PPV and may hamper clinical utility.
Acknowledgments
Automated immunoassay analyzer and reagents for PlGF were provided by PerkinElmer Life and Analytical Sciences. We would like to thank Nathalie Bernard, Mylène Badeau and Véronique Goulet for their professional assistance in the project, and our research nurses for the recruitment of participants and retrieval of data from the medical records.
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding played no role in thestudy design; in the collection, analysis, and interpretationof data; in the writing of the report; or in the decision tosubmit the report for publication.
Research funding: This work was supported by the Canadian Institutes of Health Research (CIHR, Healthy Pregnancy Initiative from the Institute for Human Development, Child and Youth Health).
Employment or leadership: YG is a research scholar from the Fonds de la recherche du Québec – Santé (FRQ-S). EB holds a Clinician Scientist Award from the CIHR and the Jeanne et Jean-Louis Lévesque Perinatal Research Chair at Université Laval.
Honorarium: None declared.
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