The fullPIERS risk prediction model for women with pre-eclampsia : external validation, recalibration and added value of a novel biomarker (placental growth factor)

The hypertensive disorders of pregnancy (HDPs), including pre-eclampsia, complicate up to 10% of pregnancies and are leading causes of maternal and perinatal morbidity and mortality. The fullPIERS model was developed to identify and quantify the risks of developing complications for women with pre-eclampsia in high-resource settings and to aid clinicians in managing such pregnancies. Prior to introducing the model into clinical practice, it is important to assess its external validity. Recalibration, if required, and addition of new biomarkers may be helpful to improve the predictive performance of the model. The objectives of this thesis were (i) to assess the external validity of the fullPIERS risk prediction model for women with pre-eclampsia (ii) recalibrate the model if necessary, and (iii) to assess the incremental value of adding the biomarker, placental growth factor (PlGF), to the model. Using abstracted medical records of women admitted into tertiary units in four high-income countries (HICs), the fullPIERS model was assessed for geographical and temporal validity. The model’s predictive ability in women with a broader spectrum of disease including early-onset pre-eclampsia, other HDPs and low and middle-income countries was also assessed using existing cohorts. Good performance was interpreted based on discrimination (AUROCs ≥0.7) and calibration (slope ≥ 0.7). Stratification and classification accuracy of the model were also assessed. The fullPIERS model showed good discriminatory performance on temporal and geographical validity (AUROCs >0.8) and also in broader HDPs (AUROCs >0.7). Medium to high likelihood ratios were estimated (>5 to >10) at a predicted probability cut-off of ≥30% for ruling in adverse maternal outcomes. Calibration was reduced in all cohorts (