Angiogenic biomarkers for prediction of early preeclampsia onset in high-risk women

Abstract

Objective: Chronic hypertension, pregestational diabetes mellitus, history of prior preeclampsia and obese nulliparity are maternal conditions associated with increased preeclampsia risk. Whether altered maternal angiogenic factor levels allow for prediction of pending disease is unclear. Our objective was to evaluate angiogenic factors for early preeclampsia prediction in high-risk women.

Methods: Serial serum specimens were collected from 157 women at high preeclampsia risk and 50 low-risk controls between 23 and 36 weeks gestation in 3 windows (23–27.6, 28–31.6, and 32–35.6 weeks) in a two-center observational cohort. Soluble fms-like tyrosine kinase-1 (sFlt1), placental growth factor (PlGF) and soluble endoglin (sEng) were measured by ELISA.

Results: Multivariate parsimonious logistic regression analyses using backward elimination for prediction of early-preeclampsia (diagnosed < 34 weeks) found the best-fitting model included the predictors (1) sFlt1 measured in the second window (28–31.6 weeks) with AUC 0.85, sensitivity 67% and specificity 96% and (2) sFlt1 measured in the first window (23–27.6 weeks) and sEng change between first and second window with AUC 0.91, sensitivity 86% and specificity 96%.

Conclusions: Two-stage sampling screening protocol utilizing sFlt1 and sEng is promising for prediction of preeclampsia diagnosed before 34 weeks. Larger studies are needed to confirm these findings.

• Angiogenic factors
• placenta growth factor (PlGF)
• preeclampsia
• soluble endoglin (sEng)
• soluble fms-like tyrosine kinase 1 (sFlt1)

Declaration of interests

Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number(s) UL1RR031982 and UL1TR000161, and by the Wilson Genetics Endowment of the George Washington University School of Medicine and Health Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. Dr. Maynard is named as a co-inventor on a patent filed by Beth Israel Deaconess Medical Center for the use of angiogenesis-related proteins for diagnosis and treatment of preeclampsia. All other authors declare no conflicts of interests. The authors alone are responsible for the content and writing of this article. A portion of the findings in this manuscript were presented at the Society for Gynecologic Investigation 59th Annual Scientific Meeting, San Diego, CA, March 21–24, 2012 and published in the supplementary edition of Reproductive Sciences as follows:

1. Maynard S, Crawford S, Bathgate S, et al. Mid-gestation angiogenic biomarker levels are increased in women at high-risk for preeclampsia. Reprod Sci 2012:19, No 3 (Supplement): T–326.

2. Moore Simas T, Crawford S, Bathgate S, et al. Angiogenic biomarkers are altered prior to preeclampsia onset in high-risk women. Reprod Sci 2012;19, No 3 (Supplement): T–327.

3. Maynard S, Crawford S, Bathgate S, et al. Mid-gestation angiogenic biomarker levels are increased in women at high-risk for preeclampsia. Society for Gynecologic Investigation (SGI) 59th Annual Scientific Meeting, San Diego, CA, March 21–24, 2012.

4. Moore Simas T, Crawford S, Bathgate S, et al. Angiogenic biomarkers are altered prior to preeclampsia onset in high-risk women. Society for Gynecologic Investigation (SGI) 59th Annual Scientific Meeting, San Diego, CA, March 21–24, 2012.

Supplementary material available online Supplementary Figure S1