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Changing antiepilepsy drug-prescribing trends in women with epilepsy in the UK and Ireland and the impact on major congenital malformations
  1. Michael O Kinney1,
  2. James Morrow1,
  3. Chris C Patterson2,
  4. Ellen Campbell1,
  5. Aline Russell3,
  6. Henry W Smithson4,
  7. Linda Parsons5,
  8. Patrick J Morrison6,
  9. Rebecca Bromley7,8,
  10. Brenda Liggan9,
  11. Norman Delanty9,
  12. Beth Irwin1,
  13. Stephen J Hunt1,
  14. John J Craig1
  1. 1 Department of Neurology, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, County Antrim, UK
  2. 2 Centre for Public Health, Queen’s University Belfast, Institute of Clinical Sciences, Belfast, Northern Ireland, UK
  3. 3 Department of Clinical Neurophysiology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, UK
  4. 4 Department of General Practice, University College Cork Ireland, Cork, Ireland
  5. 5 Neurology Department, Luton and Dunstable Hospitals NHS Trust, Luton, UK
  6. 6 Department of Medical Genetics, Belfast City Hospital, Belfast Health and Social Care Trust, Belfast, UK
  7. 7 Royal Manchester Children’s Hospital, Central Manchester University Foundation NHS Trust, Manchester, UK
  8. 8 The Institute of Human Development, The University of Manchester, Manchester, UK
  9. 9 Department of Neurology, Beaumont Hospital, Dublin, Ireland
  1. Correspondence to Dr John J Craig, Department of Neurology, Belfast Health and Social Care Trust, Belfast BT12 6BA, UK; john.craig{at}


Objectives After 20 years of data collection, pregnancy registers have informed prescribing practice. Various populations show trends for a reduction in valproate prescribing, which is associated with an increased risk of anatomical teratogenesis and neurodevelopmental effects in those exposed in utero. Our aim was to determine if any shifts in prescribing trends have occurred in the UK and Ireland Epilepsy and Pregnancy Register cohort and to assess if there had been any change in the overall major congenital malformation (MCM) rate over time.

Methods The UK and Ireland Epilepsy and Pregnancy Register, a prospective, observational, registration and follow-up study established in 1996, was used to determine the changes in antiepileptic drugs (AEDs) utilised during pregnancy and the MCM rate between 1996 and 2016. Linear regression analysis was used to assess changes in AED utilisation, and Poisson regression was used for the analysis of trends in the MCM rates.

Results Outcome data for 9247 pregnancies showed a stable percentage of monotherapy to polytherapy prescribing habits over time. After Bonferroni correction, statistically significant (p<0.003) changes were found in monotherapy prescribing with increases in lamotrigine and levetiracetam and decreases in valproate and carbamazepine use. Between 1996 and 2016, the total MCM rate showed a 2.1% reduction per year (incidence risk ratio 0.979 (95% CIs 0.956 to 1.002) but Poisson regression analysis showed that this was not statistically significant p=0.08).

Conclusion Significant changes are seen in the prescribing habits in this cohort over 20 years, but a statistically significant change in the MCM rate was not detected. This work should be replicated on a larger scale to determine if significant changes are occurring in the MCM rate, which would allow a robust economic estimate of the benefits of improvements in prescribing practice and the personal effect of such changes.

  • epilepsy
  • obstetrics
  • neuroepidemiology

Statistics from


  • Contributors MOK wrote the first and subsequent revisions of the paper and analysed the data. JM was repsonsible for the concept for study, involved in the suggestions for data and drafting. EC was involved in data analysis and also drafting. AR, HWS, LP, PJM, RB, BL, ND, BI, SJH and JJC were involved in drafting and review of manuscript. JJC was involved in the data analysis.

  • Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests MOK has received salary support to conduct a sabbatical out of programme study from UCB paid in its entirety through the Belfast Health and Social Care Trust. JM has received unrestricted educational grants from Eisai, Glaxo Smith Kline, Novartis, Sanofi-Aventis, Pfizer and UCB for the running of the UK Epilepsy and Pregnancy Register. CCP, EC and PJM report no disclosures. AR has received a grant from UCB for funding of a research nurse (2006–2009) and received small contributions from UCB, Glaxo Smith Kline, Eisai, Forth Medical, Cyberonics and Optima Medical to cover the costs of the UK Epilepsy Surgery Meeting in Glasgow in 2011. HWS has been invited to attend advisory board meetings for NAPP and Sanofi-Aventis. LP has received honoraria for presentations from UCB. BI has received sponsorship to attend meetings and honoraria for presentations from Eisai, UCB and Sanofi-Aventis. RB has received lecture fees from Sanofi Aventis (two occasions), received on one occasion conference travel support from UCB Pharma and a single consultancy fee. She has previously provided expert testimony pertaining to fetal anticonvulsant syndrome. BL has received honoraria for attending a UCB pharma Irish Nurse Advisory Board meeting. ND has received unrestricted educational support from UCB Pharma, Eisai, GSK, Janssen-Cilag and Pfizer for running of the Irish Epilepsy Pregnancy register. SJH has received sponsorship to attend meetings from Eisai, UCB and Glaxo Smith Kline. He has also received honoraria for presentations from Pfizer and UCB. JJC has received grants to undertake research and honoraria for giving lectures from UCB-Pharma, Sanofi-Synthelabo, Glaxo Smith Kline, Janssen-Cilag, Pfizer and Eisai.

  • Ethics approval Applications granted as per local ethics boards in each area where UK and Ireland Epilepsy and pregnancy registry was established - details previously published in Morrow et al, 2006.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Requests for data sharing can be made to the corresponding author. Regarding this current paper, no residual substantial unpublished data has been withheld and it has been presented in the paper.

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