Performance of sFlt-1/PIGF Ratio for the Prediction of Perinatal Outcome in Obese Pre-Eclamptic Women

Abstract

Obese women are at high risk of developing pre-eclampsia (PE). As an altered angiogenic profile is characteristic for PE, measurement of soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PIGF) ratio in the maternal serum can be helpful for PE diagnosis, as well as for adverse perinatal outcome (APO) prediction. There is growing evidence that obesity might influence the level of sFlt-1/PIGF and, therefore, the aim of the study was the evaluation of sFlt-1/PIGF as an APO predictor in obese women with PE. Pre-eclamptic women who had an sFlt-1/PIGF measurement at the time of diagnosis were retrospectively included. Women were classified according to their pre-pregnancy body mass index (BMI) as normal weight (BMI < 25 kg/m2), overweight (BMI > 25−29.9 kg/m2) or obese (BMI ≥ 30 kg/m2). APO was defined as the occurrence of one of the following outcomes: Small for gestational age, defined as a birthweight < 3rd centile, neonatal mortality, neonatal seizures, admission to neonatal unit required (NICU) or respiratory support. A total of 141 women were included. Of them, 28 (20%) patients were obese. ROC (receiver operating characteristic) analysis revealed a high predictive value for sFlt-1/PIGF and APO across the whole study cohort (AUC = 0.880, 95% CI: 0.826−0.936; p < 0.001). However, the subgroup of obese women showed a significantly lower level of sFlt-1 and, therefore, the performance of sFlt-1/PIGF as APO predictor was poorer compared to normal or overweight PE women (AUC = 0.754, 95% CI: 0.552−0.956, p = 0.025). In contrast to normal or overweight women, a ratio of sFlt-1/PIGF < 38 could not rule out APO in women with obesity.

Keywords: (anti-)angiogenic factors; obesity; placental growth factor; preeclampsia; soluble fms-like tyrosine kinase 1.

Figure 1

Level of sFlt-1/PIGF at diagnosis in normal-weight, overweight and obese women. BMI body mass index, sFlt-1 soluble fms-like tyrosine kinase-1, PIGF placental growth factor.

Figure 2

Level of sFlt-1 at diagnosis in normal-weight, overweight and obese women. BMI body mass index, sFlt-1 soluble fms-like tyrosine kinase-1.

Figure 3

Level of PIGF at diagnosis in normal-weight, overweight and obese women. BMI body mass index, PIGF placental growth factor.

Figure 4

ROC curve for APO prediction by sFlt-1 (AUC = 0.721, 95% CI: 0.637–0.804, p < 0.001), PIGF (AUC = 0.866, 95% CI: 0.807–0.925, p < 0.001) and sFlt-1/PIGF (AUC = 0.880, 95% CI: 0.824–0.936, p < 0.001). ROC receiver operating characteristic, APO adverse perinatal outcome, sFlt-1 soluble fms-like tyrosine kinase-1, PIGF placental growth factor.

Figure 5

ROC curve for APO prediction in the subgroup of normal-weight women by sFlt-1 (AUC = 0.723, 95% CI: 0.615–0.832, p < 0.001), PIGF (AUC = 0.892, 95% CI: 0.826–0.958, p < 0.001) and sFlt-1/PIGF (AUC = 0.914, 95% CI: 0.857–0.972, p < 0.001). ROC receiver operating characteristic, APO adverse perinatal outcome, sFlt-1 soluble fms-like tyrosine kinase-1, PIGF placental growth factor.

Figure 6

ROC curve for APO prediction in the subgroup of overweight women by sFlt-1 (AUC = 0.721, 95% CI: 0.531–0.910, p = 0.046), PIGF (AUC = 0.912, 95% CI: 0.811–1.000, p < 0.001) and sFlt-1/PIGF (AUC = 0.931, 95% CI: 0.845–0.999, p < 0.001). ROC receiver operating characteristic, APO adverse perinatal outcome, sFlt-1 soluble fms-like tyrosine kinase-1, PIGF placental growth factor.

Figure 7

ROC curve for APO prediction in the subgroup of obese women by sFlt-1 (AUC = 0.642, 95% CI: 0.428–0.855, p = 0.213), PIGF (AUC = 0.781, 95% CI: 0.596–0.966, p = 0.014) and sFlt-1/PIGF (AUC = 0.754, 95% CI: 0.552–0.956, p = 0.025). ROC receiver operating characteristic, APO adverse perinatal outcome, sFlt-1 soluble fms-like tyrosine kinase-1, PIGF placental growth factor.

Figure 8

ROC curve for AMO prediction by sFlt-1 (AUC = 0.694, 95% CI: 0.598–0.790, p = 0.001), PIGF (AUC = 0.605, 95% CI: 0.495–0.715, p = 0.061) and sFlt-1/PIGF (AUC = 0.667, 95% CI: 0.566–0.768, p = 0.003). ROC receiver operating characteristic, APO adverse perinatal outcome, sFlt-1 soluble fms-like tyrosine kinase-1, PIGF placental growth factor.