Placental growth factor for the prognosis of women with preeclampsia (fullPIERS model extension): context matters

Abstract

Background The fullPIERS risk prediction model was developed to identify which women admitted with confirmed diagnosis of preeclampsia are at highest risk of developing serious maternal complications. The model discriminates well between women who develop (vs. those who do not) adverse maternal outcomes. It has been externally validated in several populations. We assessed whether placental growth factor (PlGF), a biomarker associated with preeclampsia risk, adds incremental value to the fullPIERS model. Methods Using a cohort of women admitted into tertiary hospitals in well-resourced settings (the USA and Canada), between May 2010 to February 2012, we evaluated the incremental value of PlGF added to fullPIERS for prediction of adverse maternal outcomes within 48 h after admission with confirmed preeclampsia. The discriminatory performance of PlGF and the fullPIERS model were assessed in this cohort using the area under the receiver’s operating characteristic curve (AUROC) while the extended model (fullPIERS +PlGF) was assessed based on net reclassification index (NRI) and integrated discrimination improvement (IDI) performances. Results In a cohort of 541 women delivered shortly (< 1 week) after presentation, 8.1% experienced an adverse maternal outcome within 48 h of admission. Prediction of adverse maternal outcomes was not improved by addition of PlGF to fullPIERS (NRI: -8.7, IDI − 0.06). Discriminatory performance (AUROC) was 0.67 [95%CI: 0.59–0.75] for fullPIERS only and 0.67 [95%CI: 0.58–0.76]) for fullPIERS extended with PlGF, a performance worse than previously documented in fullPIERS external validation studies (AUROC > 0.75). Conclusions While fullPIERS model performance may have been affected by differences in healthcare context between this study cohort and the model development and validation cohorts, future studies are required to confirm whether PlGF adds incremental benefit to the fullPIERS model for prediction of adverse maternal outcomes in preeclampsia in settings where expectant management is practiced.

Biomolecular Markers of Recurrent Implantation Failure—A Review

“…PlGF is reported to be associated with pathological angiogenesis, which occurs in inflammatory processes and tumor angiogenesis [ 79 ]. The decreasing concentration of PlGF in preeclamptic women suggests that this molecule could predict occurrence of the disease [ 80 , 81 ]. It was suggested that PlGF could play an important role in uterine NK cell proliferation, as well as in differentiation.…”

Clinical utility of sFlt‐1 and PlGF in screening, prediction, diagnosis and monitoring of pre‐eclampsia and fetal growth restriction

“…Ukah et al 79 assessed in an extension cohort whether adding maternal PlGF concentration improved the performance of the fullPIERS model, reporting an AUC of 0.67 (95% CI, 0.58-0.76), lower than that reported previously for the fullPIERS model alone (AUC > 0.70) 59,[79][80][81] . The median gestational age at delivery was lower in the extension cohort for which maternal PlGF concentrations were available, compared with the original fullPIERS cohort (33.9 vs 36.9 weeks) 79 . Nevertheless, a Spanish multicenter, randomized controlled trial 82 demonstrated that using an algorithm based on maternal PlGF level to determine the optimal time for delivery in women with late-onset preterm PE resulted in a lower rate of progression to severe PE (adjusted relative risk (aRR), 0.5 (95% CI, 0.33-0.76), P = 0.001) without an increase in neonatal morbidity (aRR, 0.77 (95% CI, 0.39-1.53), P = 0.45), compared with women under expectant management.…”

“…The fullPIERS model has been validated in several populations and is recommended in current NICE guidelines 30 . Ukah et al 79 . assessed in an extension cohort whether adding maternal PlGF concentration improved the performance of the fullPIERS model, reporting an AUC of 0.67 (95% CI, 0.58–0.76), lower than that reported previously for the fullPIERS model alone (AUC > 0.70) 59,79–81 .…”

“…Ukah et al 79 . assessed in an extension cohort whether adding maternal PlGF concentration improved the performance of the fullPIERS model, reporting an AUC of 0.67 (95% CI, 0.58–0.76), lower than that reported previously for the fullPIERS model alone (AUC > 0.70) 59,79–81 . The median gestational age at delivery was lower in the extension cohort for which maternal PlGF concentrations were available, compared with the original fullPIERS cohort (33.9 vs 36.9 weeks) 79 .…”

Longitudinal assessment of angiogenic markers in prediction of adverse outcome in women with confirmed pre‐eclampsia

“…This finding might be explained by the cohort of women with both early‐ and late‐onset PE included in this study. The fullPIERS group 44 also evaluated their model regarding PlGF assessment and prediction of adverse outcome, but could not demonstrate improved performance of their model when maternal serum PlGF was added. This was explained by intervention bias, as expectant management was not the preferred strategy of care in their cohort.…”