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fullPIERS (Pre-eclampsia Integrated Estimate of RiSk): external validation and recalibration

Background

The fullPIERS model was developed and internally validation in a cohort of 2023 women with pre-eclampsia admitted to tertiary perinatal units in Canada, the UK, New Zealand and Australia. With good stratification capacity and predictive performance (AUC ROC: 0.88), the fullPIERS model needs to be validated externally, and then recalibrated, using external datasets.

Using the 2012 CIHR Knowledge Translation Award to Peter von Dadelszen, Vivian Ukah, herself a recipient of a UBC Four Year Fellowship (FYF), was recruited to to undertake the external validation and recalibration of the fullPIERS model, including addition of translational biomarkers, for for her PhD.

Following baseline recalibration of the fullPIERS model using the initial dataset with novel methodology developed by Beth Payne primarily for her miniPIERS-focussed PhD thesis, the plan is to update the BC Women’s Hospital cohort of women admitted with any hypertensive disorder of pregnancy, and to import data from extant datasets that will inform the model.

The integration of placental growth factor (PlGF) into fullPIERS will become a priority should the Brazilian Grand Challenges preterm birth operating grant be awarded (see Objective Four), as that study will use both PlGF and fullPIERS to risk stratify women with pre-eclampsia in that study.

Updates

Ethical approval, data sharing agreements and data collection of external, relevant datasets has been completed. These include the Alere-funded PELICAN and PETRA cohorts,  FINNPEC Finland data and the John Radcliffe Hospital, Oxford, UK dataset, for the temporal and external validation of the model. We also received cohorts from the PREP UK study and the Dutch PETRA study for broader assessment of the model. Data were also collected from the British Columbia Women’s hospital (BCW) for the validation study. For the extension of the fullPIERS model with biomarker, we will be incorporating PlGF to the model using the PELICAN and PETRA studies which have measured maternal blood levels of PlGF. We hypothesise that PlGF will improve the identification of women at risk of complications from pre-eclampsia. This has been supported by our recent finding using data on PlGF collected in Mozambique from women with suspected pre-eclampsia. In that study, low PlGF was associated with adverse outcomes such as stillbirth, Caesarean delivery and delivery within seven and fourteen days of bPlGF testing. The manuscript for this study has been published.

The fullPIERS model had good performance upon temporal and external validation with AUC ROC of 0.82 (95% CI 0.76–0.87) and 0.81 (95% CI 0.75–0.86), respectively, with a moderate calibration.

Goal

We plan to finalise all data analyses and writing of manuscripts. Published papers include:

  • The diagnostic performance of placental growth factor in women with suspected pre-eclampsia attending antenatal facilities in Maputo, Mozambique. Hypertension 2017;69(3):469-474.
  • External validation of the fullPIERS model for predicting adverse outcomes in women with hypertensive disorders of pregnancy: a validation study. Hypertension 2017;69:705-711

Expected publications include:

  • External and Temporal validation of the fullPIERS model in High-income countries using the BCW cohort combined with FINNPEC, Alere-funded PETRA and PELICAN and Oxford datasets.
  • Broader assessment of the fullPIERS model in women with early onset pre-eclampsia using the combined PREP, and Dutch-PETRA datasets.
  • Addition and assessment of PlGF in the fullPIERS model.
  • Recalibration of the fullPIERS model for better performance, in the context of a methodology paper, using external datasets.