Altered Hemodynamics and Hyperuricemia Accompany an Elevated sFlt-1/PlGF Ratio Before the Onset of Early Severe Preeclampsia

Abstract

Objectives

Early identification of women at risk of developing early-onset severe preeclampsia (sPE) is a key objective in obstetrics. An elevated ratio of serum soluble fms-like tyrosine kinase (sFlt-1) to placenta-like growth factor (PlGF) (sFlt-1/PlGF ratio) precedes overt hypertension. The longitudinal relationship between this biomarker, maternal hemodynamics, and maternal serum uric acid during the pre-clinical phase is unknown.

Study Design

We followed 20 normotensive women at high risk of developing sPE from 20 weeks until delivery or 34 weeks' gestation. Non-invasive hemodynamic monitoring using bioreactance technology was performed at 20 to 22, 24 to 26, 28 to 30, and 32 to 34 weeks' gestation. Serum uric acid, sFlt-1, and PlGF were measured simultaneously.

Results

Six of 20 women (30%) delivered before 33 weeks with sPE and had significantly higher mean total peripheral resistance (TPR), higher serum uric acid, and higher sFlt-1/PlGF ratios at 24 weeks' gestation than unaffected individuals. The area under the curve, cut-off values, and sensitivity and specificity to predict sPE at 24 weeks were as follows: TPR 0.84, 1250 dyne.s.cm^-5, 80%, 93%; sFlt-1/PlGF ratio 0.94, 55, 100%, 93%; and serum uric acid 0.99, 255 μmol/L, 100%, 93%. TPR and sFlt-1 were positively correlated in the sPE group before antihypertensive treatment (r=0.65, P=0.01). Serum uric acid correlated with both sFlt-1 (r=0.65, P=0.003) and sFlt-1/PlGF ratio (r=0.54, P=0.02).

Conclusion

A combination of non-invasive determination of TPR together with measurement of serum uric acid may identify a subset of clinically high-risk women with evolving sPE, independent of the determination of the sFlt-1/PlGF ratio. The predictive ability of this integrated approach needs to be assessed in a larger cohort of women to further confirm its utility.