The online version of this article (doi:10.1186/s12916-017-0827-3) contains supplementary material, which is available to authorized users.
Unexpected clinical deterioration before 34 weeks gestation is an undesired course in early-onset pre-eclampsia. To safely prolong preterm gestation, accurate and timely prediction of complications is required.
Women with confirmed early onset pre-eclampsia were recruited from 53 maternity units in the UK to a large prospective cohort study (PREP-946) for development of prognostic models for the overall risk of experiencing a complication using logistic regression (PREP-L), and for predicting the time to adverse maternal outcome using a survival model (PREP-S). External validation of the models were carried out in a multinational cohort (PIERS-634) and another cohort from the Netherlands (PETRA-216). Main outcome measures were C-statistics to summarise discrimination of the models and calibration plots and calibration slopes.
A total of 169 mothers (18%) in the PREP dataset had adverse outcomes by 48 hours, and 633 (67%) by discharge. The C-statistics of the models for predicting complications by 48 hours and by discharge were 0.84 (95% CI, 0.81–0.87; PREP-S) and 0.82 (0.80–0.84; PREP-L), respectively. The PREP-S model included maternal age, gestation, medical history, systolic blood pressure, deep tendon reflexes, urine protein creatinine ratio, platelets, serum alanine amino transaminase, urea, creatinine, oxygen saturation and treatment with antihypertensives or magnesium sulfate. The PREP-L model included the above except deep tendon reflexes, serum alanine amino transaminase and creatinine. On validation in the external PIERS dataset, the reduced PREP-S model showed reasonable calibration (slope 0.80) and discrimination (C-statistic 0.75) for predicting adverse outcome by 48 hours. Reduced PREP-L model showed excellent calibration (slope: 0.93 PIERS, 0.90 PETRA) and discrimination (0.81 PIERS, 0.75 PETRA) for predicting risk by discharge in the two external datasets.
PREP models can be used to obtain predictions of adverse maternal outcome risk, including early preterm delivery, by 48 hours (PREP-S) and by discharge (PREP-L), in women with early onset pre-eclampsia in the context of current care. They have a potential role in triaging high-risk mothers who may need transfer to tertiary units for intensive maternal and neonatal care.
ISRCTN40384046, retrospectively registered.
Additional file 1: Table S1. Definition of the inclusion criteria for women recruited in the PREP study. Table S2. Crude univariable and multivariable analyses of candidate predictors and adverse fetal outcomes in women with early onset pre-eclampsia. Table S3. Definitions of the individual components of the composite outcomes evaluated in the PREP study*. Table S4. Changes since original application. Table S5. Rates of individual complications in women with early onset pre-eclampsia in the PREP study. Table S6. Characteristics of predictors available in the PREP study and external validation cohorts (PIERS and PETRA). (DOCX 43 kb)
MacKay AP, Berg CJ, Atrash HK. Pregnancy-related mortality from preeclampsia and eclampsia. Obstet Gynecol. 2001;97(4):533–8. PubMed
von Dadelszen P, Magee LA, Roberts JM. Subclassification of preeclampsia. Hypertens Pregnancy. 2003;22(2):143–8. CrossRef
von Dadelszen P, Menzies JM, Payne B, Magee LA, PIERS (Pre-eclampsia Integrated Estimate of RiSk) Study Group. Predicting adverse outcomes in women with severe pre-eclampsia. Semin Perinatol. 2009;33(3):152–7. CrossRef
von Dadelszen P, Payne B, Li J, Ansermino JM, Broughton-Pipkin F, Cote AM, Douglas MJ, Gruslin A, Hutcheon JA, Joseph KS, Kyle PM, Lee T, Loughna P, Menzies JM, Merialdi M, Millman AL, Moore MP, Moutquin JM, Ouellet AB, Smith GN, Walker JJ, Walley KR, Walters BN, Widmer M, Lee SK, Russell JA, Magee LA, PIERS Study Group. Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model. Lancet. 2011;377(9761):219–27. CrossRef
Churchill D, Duley L. Interventionist versus expectant care for severe pre-eclampsia before term. Cochrane Database Syst Rev. 2002;3:CD003106.
World Health Organization. WHO recommendations for prevention and treatment of pre-eclampsia and eclampsia. Geneva: WHO; 2011.
High Dependency Care for Children - Time To Move On. A focus on the critically ill child pathway beyond the Paediatric Intensive Care Unit. 2014. http://www.rcpch.ac.uk/sites/default/files/page/HDC%20for%20web.pdf. Accessed 30 Aug 2016.
Ganzevoort W, Rep A, Bonsel GJ, De Vries JI, Wolf H, PETRA investigators. A randomized trial of plasma volume expansion in hypertensive disorders of pregnancy: influence on the pulsatility indices of the fetal umbilical artery and middle cerebral artery. Am J Obstet Gynecol. 2005;192(1):233–9. CrossRefPubMed
Project Portfolio. HTA - 09/22/163: Development and validation of a Prediction model for Risk of complications in Early onset Pre eclampsia (PREP). http://www.nets.nihr.ac.uk/projects/hta/0922163. Accessed 30 Nov 2015.
Hypertension in Pregnancy: The management of hypertensive disorders during pregnancy. NICE Clinical Guideline. 2010. https://www.nice.org.uk/guidance/cg107. Accessed 12 Feb 2015.
Lambert PC, Royston P. Further development of flexible parametric models for survival analysis. Stata J. 2009;9(2):265–90.
Royston P, Lambert PC. Flexible Parametric Survival Analysis Using Stata: Beyond the Cox Model. College Station, TX: Stata Press; 2011.
StataCorp. Stata Statistical Software: Release 12. College Station, TX: StataCorp LP; 2011.
Rubin DB. Multiple Imputation for Nonresponse in Surveys. New York: Wiley; 1987. CrossRef
Royal College of Obstetricians and Gynaecologists. Magnesium Sulphate to Prevent Cerebral Palsy following Preterm Birth (Scientific Impact Paper No. 29). https://www.rcog.org.uk/globalassets/documents/guidelines/scientific-impact-papers/sip_29.pdf. Accessed 14 Jan 2016.
Allotey J, Marlin N, Mol B, et al. Development and validation of prediction models for risk of adverse outcomes in women with early-onset pre-eclampsia: protocol of the prospective cohort PREP study. Diagn Prognostic Res. 2017. In press.
Payne BA, Hutcheon JA, Ansermino JM, et al. A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) multi-country prospective cohort study. PLoS Med. 2014;11(1):e1001589. CrossRefPubMedPubMedCentral
Thangaratinam S, Allotey J, Marlin N, et al. Development and validation of a prediction model for the risk of adverse outcomes in women with early onset pre-eclampsia (PREP): Prospective cohort study. Health Technol Assess. 2016. In Press.
Widmer M, Cuesta C, Khan KS, et al. Accuracy of angiogenic biomarkers at 20 weeks’ gestation in predicting the risk of pre-eclampsia: a WHO multicentre study. Pregnancy Hypertens. 2015;5(4):330–8. PubMed
- Prediction of complications in early-onset pre-eclampsia (PREP): development and external multinational validation of prognostic models
Peter von Dadelszen
Ben W. Mol
Karl G. M. Moons
Richard D. Riley
Khalid S. Khan
for the PREP Collaborative Network
- BioMed Central
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