The performance of pre-delivery serum concentrations of angiogenic factors in predicting postpartum antihypertensive drug therapy following abdominal delivery in severe preeclampsia and normotensive pregnancy

Abstract

Background The imbalance between circulating concentrations of anti- and pro-angiogenic factors is usually intense in preeclampsia with severe features (sPE). It is possible that pre-delivery circulating levels of angiogenic factors in sPE may be associated with postpartum antihypertensive drug requirements. Objective To determine the predictive association between maternal pre-delivery serum concentrations of angiogenic factors and the use of 3 slow- and/or a rapid-acting antihypertensive drug therapy in sPE on postpartum days zero to three following caesarean delivery. Study design Women with sPE (n = 50) and normotensive pregnancies (n = 90) were recruited prior to childbirth. Serum samples were obtained from each participant < 48 hours before delivery to assess the concentrations of placental growth factor (PIGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) using the Roche Elecsys platform. Each participant was followed up on postpartum days zero, one, two and three to monitor BP and confirm antihypertensive treatment. The optimal cut-off thresholds of sFlt-1/PIGF ratio from receiver operating characteristic curve predictive of the antihypertensive therapy were subjected to diagnostic accuracy assessment. Results The majority 58% (29/50) of sPE had multiple severe features of preeclampsia in the antenatal period with the commonest presentation being severe hypertension in 88% (44/50) of this group, followed by features of impending eclampsia which occurred in 42% (21/50). The median gestational age at delivery was 38 (Interquartile range, IQR 1) vs 36 (IQR 6) weeks, p < 0.001 in normotensive and sPE groups respectively. Notably, the median sFlt-1/PIGF ratio in normotensive and sPE groups were 7.3 (IQR 17.9) and 179.1 (IQR 271.2) respectively, p < 0.001. Of the 50 sPE participants, 34% (17/50) had early-onset preeclampsia. The median (IQR) of sFlt-1/PIGF in the early- and late-onset preeclampsia groups were 313.52 (502.25), and 166.59(195.37) respectively, p = 0.006. From postpartum days zero to three, 48% (24/50) of sPE received 3 slow- and/or a rapid-acting antihypertensive drug. However, the daily administration of 3 slow- and/or a rapid-acting antihypertensive drug in sPE were pre-delivery 26% (13/50), postpartum day zero 18% (9/50), postpartum day one 34% (17/50), postpartum day two 24% (12/50) and postpartum day three 20% (10/50). In sPE, the pre-delivery sFlt-1/PIGF ratio was predictive of administration of 3 slow- and/or a rapid-acting antihypertensive drug on postpartum days zero, one and two with the optimal cut-off ratio being 315.0, 181.5 and 267.8 respectively (sensitivity 72.7–75.0%, specificity 64.7–78.6%, positive predictive value 40.0–50.0% and negative predictive value 84.6% - 94.3%). The predictive performance of sFlt-1/PIG ratio on postpartum day 3 among the sPE was not statistically significant (area under receiver operating characteristic curve, 0.6; 95% CI, 0.3–0.8). Conclusion A pre-delivery sFlt-1/PIGF ratio (< 181.5) is a promising predictor for excluding the need for 3 slow- and/or a rapid-acting antihypertensive drug therapy in the immediate postpartum period in sPE.