Role of placental, fetal and maternal cardiovascular markers in predicting adverse outcome in women with suspected or confirmed pre‐eclampsia
Authors: Reddy M. , Palmer K. , Rolnik D. L. , Wallace E. M. , Mol B. W. , Da Silva Costa F. 
Published: January 2022

Objective

To assess the performance of placental, fetal and maternal cardiovascular markers in the prediction of adverse perinatal and maternal outcomes in women with suspected or confirmed pre‐eclampsia.

Methods

This was a prospective prognostic accuracy study of women with suspected or confirmed pre‐eclampsia who underwent a series of investigations to measure maternal hemodynamic indices, mean arterial pressure, augmentation index, ophthalmic artery peak systolic velocity (PSV) ratio, uterine artery pulsatility index (UtA‐PI), fetal biometric and Doppler parameters, soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF). The performance of these markers, individually or in combination, in predicting adverse perinatal and maternal outcomes was then assessed using receiver‐operating‐characteristics (ROC)‐curve analysis. Adverse maternal outcome was defined as one or more of severe hypertension, admission to the intensive care unit, eclampsia, placental abruption, HELLP syndrome, disseminated intravascular coagulation, platelets < 100 × 109/L, creatinine > 90 μmol/L and alanine aminotransferase > 100 U/L. Adverse perinatal outcome was defined as one or more of preterm birth at or before 34 + 0 weeks, neonatal intensive care unit admission for > 48 h, respiratory distress syndrome, intraventricular hemorrhage, hypoxic ischemic encephalopathy, necrotizing enterocolitis, retinopathy of prematurity and confirmed fetal infection.

Results

We recruited 126 women with suspected (n = 31) or confirmed (n = 95) pre‐eclampsia at a median gestational age of 33.9 weeks (interquartile range, 30.9–36.3 weeks). Pregnancies with adverse perinatal outcome compared to those without had a higher median UtA‐PI (1.3 vs 0.8; P < 0.001), ophthalmic artery PSV ratio (0.8 vs 0.7; P = 0.01) and umbilical artery PI percentile (82.0 vs 68.5; P < 0.01) and lower median estimated fetal weight percentile (4.0 vs 43.0; P < 0.001), abdominal circumference percentile (4.0 vs 63.0; P < 0.001), middle cerebral artery PI percentile (28.0 vs 58.5; P < 0.001) and cerebroplacental ratio percentile (18.0 vs 46.5; P < 0.001). Pregnancies with adverse perinatal outcome also had a higher median sFlt‐1 (8208.0 pg/mL vs 4508.0 pg/mL; P < 0.001), lower PlGF (27.2 pg/mL vs 76.3 pg/mL; P < 0.001) and a higher sFlt‐1/PlGF ratio (445.4 vs 74.4; P < 0.001). The best performing individual marker for predicting adverse perinatal outcome was the sFlt‐1/PlGF ratio (area under the ROC curve (AUC), 0.87 (95% CI, 0.81–0.93)), followed by estimated fetal weight (AUC, 0.81 (95% CI, 0.73–0.89)). Women who experienced adverse maternal outcome had a higher median sFlt‐1 level (7471.0 pg/mL vs 5131.0 pg/mL; P < 0.001) and sFlt‐1/PlGF ratio (204.3 vs 93.3; P < 0.001) and a lower PlGF level (37.0 pg/mL vs 66.1 pg/mL; P = 0.01) and estimated fetal weight percentile (16.5 vs 37.0; P = 0.04). All markers performed poorly in predicting adverse maternal outcome, with sFlt‐1 (AUC, 0.69 (95% CI, 0.60–0.79)) and sFlt‐1/PlGF ratio (AUC, 0.69 (95% CI, 0.59–0.78)) demonstrating the best individual performance. The addition of cardiovascular, fetal or other placental indices to the sFlt‐1/PlGF ratio did not improve the prediction of adverse maternal or perinatal outcomes.

Conclusions

The sFlt‐1/PlGF ratio performs well in predicting adverse perinatal outcomes but is a poor predictor of adverse maternal outcomes in women with suspected or diagnosed pre‐eclampsia. The addition of cardiovascular or fetal indices to the model is unlikely to improve the prognostic performance of the sFlt‐1/PlGF ratio. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.