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Prognostic indicators of severe disease in women with late preterm preeclampsia to guide decision making on timing of delivery: development and validation of prognostic models
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  • Kate Duhig,
  • Paul Seed,
  • Anna Placzek,
  • Jenie Sparkes,
  • Eleanor Hendy,
  • Carolyn Gill,
  • Anna Brockbank,
  • Andrew Shennan,
  • Shakila Thangaratinam,
  • Lucy Chappell
Kate Duhig
Kings College London

Corresponding Author:kate.duhig@kcl.ac.uk

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Paul Seed
Kings College London
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Anna Placzek
University of Oxford
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Jenie Sparkes
Kings College London
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Eleanor Hendy
Kings College London
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Carolyn Gill
Kings College London
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Anna Brockbank
Kings College London
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Andrew Shennan
Kings College London
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Shakila Thangaratinam
WHO Collaborating Centre for Women's Health
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Lucy Chappell
King's College London
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Abstract

Objective: to establish a prognostic model informing optimal timing of delivery in women with late preterm preeclampsia. Design: development and validation of a prognostic model Setting: prospective cohort study, nested in the PHOENIX trial, in 36 maternity units across England and Wales. Population: women with late preterm pre-eclampsia (34+0-36+6 weeks’ gestation) Methods: prospective recruitment of women in whom blood samples for Placental Growth Factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) testing was obtained, alongside clinical data, for use within the ‘Prediction of complications in early-onset pre-eclampsia’ (PREP)-S model. Candidate variables were compared using standard methods (sensitivity, specificity, Receiver Operator Curve areas). Estimated probability of early delivery from PREP-S was compared to actual event rates by calibration. Main Outcome Measures: clinically indicated need for delivery for pre-eclampsia within seven days. Results: PlGF testing had high sensitivity (97.9%) for delivery within seven days, but negative predictive value was only 71.4%, with low specificity (8.4%). The area under the curve for PREP-S was 0.64 (standard error (SE) 0.03), for PlGF was 0.60 (SE 0.03), and 0.65 (0.03), and 0.64 (0.03) for PREP-S in combination with PlGF and sFlt-1:PlGF, respectively. Conclusions: PlGF-based testing does not add to clinical assessment to determine need for delivery in late preterm pre-eclampsia. Existing models developed in women with early onset pre-eclampsia to predict complications cannot be used to predict clinically indicated need for delivery in women with late preterm pre-eclampsia. Funding: NIHR HTA Monitoring Add on Studies Programme (reference 15/59/06). Keywords: placental growth factor, preeclampsia, prognosis