Altered hemodynamics and hyperuricemia accompany an elevated sFlt-1/PlGF ratio before the onset of early severe preeclampsia

Anne Doherty, Jose C A Carvalho, Sascha Drewlo, Afif El-Khuffash, Kristi Downey, Madelaine Dodds, John Kingdom
Journal of Obstetrics and Gynaecology Canada: JOGC 2014, 36 (8): 692-700

OBJECTIVE: 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, 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.

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