Predicting seizures in pregnant women with epilepsy: development and external validation of a prognostic model

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dc.contributor.authorAllotey, J.
dc.contributor.authorFernandez-Felix, B.M.
dc.contributor.authorZamora, J.
dc.contributor.authorMoss, N.
dc.contributor.authorBagary, M.
dc.contributor.authorKelso, A.
dc.contributor.authorKhan, R.
dc.contributor.authorvan der Post, J.A.M.
dc.contributor.authorMol, B.W.
dc.contributor.authorPirie, A.M.
dc.contributor.authorMcCorry, D.
dc.contributor.authorKhan, K.S.
dc.contributor.authorThangaratinam, S.
dc.contributor.editorChappell, L.C.
dc.date.issued2019
dc.description.abstractBACKGROUND:Seizures are the main cause of maternal death in women with epilepsy, but there are no tools for predicting seizures in pregnancy. We set out to develop and validate a prognostic model, using information collected during the antenatal booking visit, to predict seizure risk at any time in pregnancy and until 6 weeks postpartum in women with epilepsy on antiepileptic drugs. METHODS AND FINDINGS:We used datasets of a prospective cohort study (EMPiRE) of 527 pregnant women with epilepsy on medication recruited from 50 hospitals in the UK (4 November 2011-17 August 2014). The model development cohort comprised 399 women whose antiepileptic drug doses were adjusted based on clinical features only; the validation cohort comprised 128 women whose drug dose adjustments were informed by serum drug levels. The outcome was epileptic (non-eclamptic) seizure captured using diary records. We fitted the model using LASSO (least absolute shrinkage and selection operator) regression, and reported the performance using C-statistic (scale 0-1, values > 0.5 show discrimination) and calibration slope (scale 0-1, values near 1 show accuracy) with 95% confidence intervals (CIs). We determined the net benefit (a weighted sum of true positive and false positive classifications) of using the model, with various probability thresholds, to aid clinicians in making individualised decisions regarding, for example, referral to tertiary care, frequency and intensity of monitoring, and changes in antiepileptic medication. Seizures occurred in 183 women (46%, 183/399) in the model development cohort and in 57 women (45%, 57/128) in the validation cohort. The model included age at first seizure, baseline seizure classification, history of mental health disorder or learning difficulty, occurrence of tonic-clonic and non-tonic-clonic seizures in the 3 months before pregnancy, previous admission to hospital for seizures during pregnancy, and baseline dose of lamotrigine and levetiracetam. The C-statistic was 0.79 (95% CI 0.75, 0.84). On external validation, the model showed good performance (C-statistic 0.76, 95% CI 0.66, 0.85; calibration slope 0.93, 95% CI 0.44, 1.41) but with imprecise estimates. The EMPiRE model showed the highest net proportional benefit for predicted probability thresholds between 12% and 99%. Limitations of this study include the varied gestational ages of women at recruitment, retrospective patient recall of seizure history, potential variations in seizure classification, the small number of events in the validation cohort, and the clinical utility restricted to decision-making thresholds above 12%. The model findings may not be generalisable to low- and middle-income countries, or when information on all predictors is not available. CONCLUSIONS:The EMPiRE model showed good performance in predicting the risk of seizures in pregnant women with epilepsy who are prescribed antiepileptic drugs. Integration of the tool within the antenatal booking visit, deployed as a simple nomogram, can help to optimise care in women with epilepsy.
dc.description.statementofresponsibilityJohn Allotey, Borja M. Fernandez-Felix, Javier Zamora, Ngawai Moss, Manny Bagary ... Ben W. Mol ... et al.
dc.identifier.citationPLoS Medicine, 2019; 16(5):e1002802-1-e1002802-18
dc.identifier.doi10.1371/journal.pmed.1002802
dc.identifier.issn1549-1277
dc.identifier.issn1549-1676
dc.identifier.orcidMol, B.W. [0000-0001-6887-0262] [0000-0001-8337-550X]
dc.identifier.urihttp://hdl.handle.net/2440/120715
dc.language.isoen
dc.publisherPublic Library Science
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1082548
dc.rights© 2019 Allotey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.source.urihttps://doi.org/10.1371/journal.pmed.1002802
dc.subjectBrain
dc.subjectHumans
dc.subjectEpilepsy
dc.subjectPregnancy Complications
dc.subjectAnticonvulsants
dc.subjectPrognosis
dc.subjectRisk Assessment
dc.subjectRisk Factors
dc.subjectProspective Studies
dc.subjectReproducibility of Results
dc.subjectPredictive Value of Tests
dc.subjectPregnancy
dc.subjectDecision Support Techniques
dc.subjectAdolescent
dc.subjectAdult
dc.subjectChild
dc.subjectFemale
dc.subjectYoung Adult
dc.subjectBrain Waves
dc.subjectMaternal Health
dc.titlePredicting seizures in pregnant women with epilepsy: development and external validation of a prognostic model
dc.typeJournal article
pubs.publication-statusPublished

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