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The M6 risk prediction model and two-step strategy to characterize pregnancies of unknown location: a multicentre external validation study
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  • Evangelia Christodoulou,
  • Shabnam Bobdiwala,
  • Christopher Kyriacou,
  • Jessica Farren,
  • Nicola Mitchell-Jones,
  • Francis Ayim,
  • Baljinder Chohan,
  • Osama Abughazza,
  • Bramara Guruwadahyarhalli,
  • Maya Al-Memar,
  • Sharmista Guha,
  • Veluppillai Vathanan,
  • Debbie Gould,
  • Catriona Stalder,
  • Laure Wynants,
  • Dirk Timmerman,
  • Tom Bourne,
  • Ben Van Calster
Evangelia Christodoulou
KU Leuven
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Shabnam Bobdiwala
Queen Charlotte's and Chelsea Hospital
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Christopher Kyriacou
Queen Charlotte's and Chelsea Hospital
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Jessica Farren
St Mary's Hospital
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Nicola Mitchell-Jones
Chelsea and Westminster NHS Trust
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Francis Ayim
Hillingdon Hospital
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Baljinder Chohan
Wexham Park Hospital
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Osama Abughazza
Royal Surrey County Hospital NHS Foundation Trust
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Bramara Guruwadahyarhalli
Chelsea and Westminster Healthcare NHS Trust
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Maya Al-Memar
Queen Charlotte's and Chelsea Hospital
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Sharmista Guha
Chelsea and Westminster Healthcare NHS Trust
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Veluppillai Vathanan
Wexham Park Hospital
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Debbie Gould
St Mary's Hospital
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Catriona Stalder
Queen Charlotte's and Chelsea Hospital
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Laure Wynants
KU Leuven, Maastricht University
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Dirk Timmerman
KU Leuven
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Tom Bourne
KU Leuven, Imperial College London
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Ben Van Calster
Leiden University Medical Centre, KU Leuven
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Abstract

Objective. To externally validate the M6 risk model and the two-step triage strategy (2ST) to triage pregnancies of unknown location (PUL), and compare performance with the M4 model and beta human chorionic gonadotropin (BhCG) ratio cut-offs. Design. Model validation study. Setting. Eight UK hospitals with early pregnancy assessment units. Population. Women presenting with a PUL and BhCG >25 IU/L. Methods. Women were managed using the 2ST protocol: step 1 classifies PUL as low risk of ectopic pregnancy (EP) if presenting progesterone ≤2 nmol/L, M6 is used as step 2 in the remaining cases. We validated 2ST and M6 alone (with and without progesterone as a predictor: M6P and M6NP). M6 and M4 require the BhCG ratio over two days. Based on these models, we classified PUL as high risk for EP when the risk was ≥5%. We meta-analysed centre-specific results. Main outcome measures. Discrimination, calibration and clinical utility (decision curve analysis) for predicting EP. Results. Of 2899 eligible women, the main analysis excluded 297 (10%) women that were lost to follow-up. 16% (95% confidence interval 12-20) of women had presenting progesterone ≤2 nmol/L. The area under the ROC curve for EP was 0.88 (0.86-0.90) for 2ST and 0.89 (0.86-0.91) for M6P. Sensitivity for EP was 94% (89%-97%) for 2ST and 96% (91%-98%) for M6P. Both approaches had good overall calibration, with modest variability between centres. M4 and BhCG ratio cut-offs had inferior performance and lower clinical utility. Conclusions. The 2ST and M6P alone are the best approaches to triage PUL.

Peer review status:ACCEPTED

05 Apr 2020Submitted to BJOG: An International Journal of Obstetrics and Gynaecology
07 Apr 2020Submission Checks Completed
07 Apr 2020Assigned to Editor
07 Apr 2020Reviewer(s) Assigned
26 May 2020Review(s) Completed, Editorial Evaluation Pending
17 Jun 2020Editorial Decision: Revise Major
22 Jul 20201st Revision Received
05 Aug 2020Submission Checks Completed
05 Aug 2020Assigned to Editor
05 Aug 2020Reviewer(s) Assigned
14 Aug 2020Review(s) Completed, Editorial Evaluation Pending
28 Aug 2020Editorial Decision: Accept