Development and internal validation of the multivariable CIPHER

Abstract

BackgroundIntensive care unit (ICU) outcome prediction models, such as Acute Physiology And Chronic Health Evaluation (APACHE), were designed in general critical care populations and their use in obstetric populations is contentious. The aim of the CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) study was to develop and internally validate a multivariable prognostic model calibrated specifically for pregnant or recently delivered women admitted for critical care.MethodsA retrospective observational cohort was created for this study from 13 tertiary facilities across five high-income and six low- or middle-income countries. Women admitted to an ICU for more than24h during pregnancy orless than6weeks post-partum from 2000 to 2012 were included in the cohort. A composite primary outcome was defined as maternal death or need for organ support for more than 7days or acute life-saving intervention. Model development involved selection of candidate predictor variables based on prior evidence of effect, availability across study sites, and use of LASSO (Least Absolute Shrinkage and Selection Operator) model building after multiple imputation using chained equations to address missing data for variable selection. The final model was estimated using multivariable logistic regression. Internal validation was completed using bootstrapping to correct for optimism in model performance measures of discrimination and calibration.ResultsOverall, 127 out of 769 (16.5%) women experienced an adverse outcome. Predictors included in the final CIPHER model were maternal age, surgery in the preceding 24h, systolic blood pressure, Glasgow Coma Scale score, serum sodium, serum potassium, activated partial thromboplastin time, arterial blood gas (ABG) pH, serum creatinine, and serum bilirubin. After internal validation, the model maintained excellent discrimination (area under the curve of the receiver operating characteristic (AUROC) 0.82, 95% confidence interval (CI) 0.81 to 0.84) and good calibration (slope of 0.92, 95% CI 0.91 to 0.92 and intercept of -0.11, 95% CI -0.13 to -0.08).ConclusionsThe CIPHER model has the potential to be a pragmatic risk prediction tool. CIPHER can identify critically ill pregnant women at highest risk for adverse outcomes, inform counseling of patients about risk, and facilitate bench-marking of outcomes between centers by adjusting for baseline risk.

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[Payne, Beth A.; Ansermino, J. Mark] Univ British Columbia, Dept Anesthesiol Pharmacol & Therapeut, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada.

Univ British Columbia, BC Childrens Hosp Res Inst, V3-336 950 28th Ave, Vancouver, BC V5Z 4H4, Canada.

[Payne, Beth A.; Ryan, Helen; Bone, Jeffrey; Magee, Laura A.; Ansermino, J. Mark; Hutcheon, Jennifer A.; Joseph, K. S.; Li, Jing; Liskonova, Sarka; Ukah, U. Vivian; Yong, Paul; von Dadelszen, Peter] Univ British Columbia, Womens Hlth Res Inst, V3-336 950 28th Ave, Vancouver, BC V5Z 4H4, Canada.

[Ryan, Helen] Univ British Columbia, Dept Family Practice, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada.

[Magee, Laura A.; Aarvold, Alice B.; Walley, Keith R.] Univ British Columbia, Dept Med, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada.

[Magee, Laura A.; von Dadelszen, Peter] Kings Coll London, Sch Life Course Sci, Fac Life Sci & Med, London WC2R 2LS, England.

[Bhutta, Zulfiqar A.; Qureshi, Rahat] Aga Khan Univ, Ctr Excellence Women Child Hlth, Block 2 Clifton, Karachi, Sindh, Pakistan.

[Bhutta, Zulfiqar A.] Hosp Sick Children, Ctr Global Child Hlth, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.

[Bowen, Mary; Geary, Michael] Univ Coll Dublin, Rotunda Hosp, 1 Parnell Sq E, Dublin, Ireland.

[Cecatti, J. Guilherme] Univ Estadual Campinas, Cidade Univ Zeferino Vaz Barao Geraldo, BR-13083970 Campinas, SP, Brazil.

[Chazotte, Cynthia; Goffman, Dena] Columbia Univ, Med Ctr, Montefiore Med Ctr, 951 Prospect Ave, Bronx, NY 10459 USA.

[Chazotte, Cynthia; Goffman, Dena] Morgan Stanley Childrens Hosp, 3959 Broadway, New York, NY 10032 USA.

[Chazotte, Cynthia; Goffman, Dena] Sloan Hosp Mothers, 3959 Broadway, New York, NY 10032 USA.

[Crozier, Tim; Wallace, Euan] Monash Univ, Dept Obstet & Gynaecol, Wellington Rd,Clayton 3800, Victoria, BC, Canada.

[de Pont, Anne-Cornelie J. M.; Kallen, Marlot; Ganzevoort, Wessel; Mol, Ben W. J.] Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.

[Demirkiran, Oktay; Togal, Turkan; Zhou, Vivian] Inonu Univ, TR-44000 Malatya, Battalgazi, Turkey.

[Duan, Tao] Shanghai 1st Matern & Infant Hosp, 536 Changle Rd, Shanghai 200000, Jingan Qu, Peoples R China.

[Lapinsky, Stephen E.; Seaward, P. Gareth R.] Univ Toronto, Sinai Hosp, 600 Univ Ave, Toronto, ON M5G 1X5, Canada.

[Lataifeh, Isam; Tadros, Ramzy] King Abdullah Univ Hosp, Ar Ramtha 3030, Ramtha, Jordan.

[McAuliffe, Fionnuala M.; O'Herlihy, Colm] UCD, Natl Matern Hosp, Sch Med, Perinatal Res Ctr, Dublin D14YH57, Ireland.

[Mol, Ben W. J.] Univ Adelaide, Dept Paediat & Womens Hlth, Adelaide, SA 5005, Australia.

[Vasquez, Daniela] Hosp Interzonal Gen Agudos Gral, 101 Dr Ricardo Balbin, RA-3200 Buenos Aires, DF, Argentina.

[Walley, Keith R.] St Pauls Hosp, Ctr Heart Lung Innovat, 1081 Burrard St, Vancouver, BC V6Z 1Y6, Canada.