Folic acid use and major congenital malformations in offspring of women with epilepsy: a prospective study from the UK Epilepsy and Pregnancy Register
- J I Morrow1,
- S J Hunt1,
- A J Russell2,
- W H Smithson3,
- L Parsons4,
- I Robertson5,
- R Waddell6,
- B Irwin6,
- P J Morrison7,8,
- J J Craig1
- 1 Department of Neurology, Royal Group of Hospitals, Belfast, UK
- 2 Department of Clinical Neurophysiology, Southern General Hospital, Glasgow, UK
- 3 The Surgery, Escrick, York, UK
- 4 Department of Neurology, St Albans City Hospital, St Albans, UK
- 5 Obstetrics and Gynaecology Department, Lancashire Teaching Hospitals NHS Trust, Preston, UK
- 6 Bostock House, Royal Group of Hospitals, Belfast, UK
- 7 Department of Medical Genetics, Belfast City Hospital Trust, Belfast, UK
- 8 School of Biological Sciences, University of Ulster, Coleraine, UK
- Dr J I Morrow, Department of Neurology, Royal Group of Hospitals, Grosvenor Road, Belfast BT12 6BA, UK;
- Received 18 June 2008
- Revised 13 August 2008
- Accepted 16 September 2008
- Published Online First 31 October 2008
Objective: In the general population, folic acid supplementation during pregnancy has been demonstrated to reduce the frequency of neural tube defects (NTDs) and other major congenital malformations (MCMs). It is recommended that women with epilepsy contemplating pregnancy take supplemental folic acid because of the known antifolate effect of some antiepileptic drugs (AEDs). Here the aim was to determine the effectiveness of this practice.
Methods: This study is part of a prospective, observational, registration and follow-up study. Suitable cases are women with epilepsy who become pregnant and who are referred before outcome of the pregnancy is known. The main outcome measure is the MCM rate. Outcomes were analysed against folic acid exposure, malformation type and drug group for the most commonly used monotherapy AEDs.
Results: In 1935 cases reported to have received preconceptual folic acid, 76 MCMs (3.9%; 95% CI 3.1 to 4.9) and eight NTDs (0.4%; 95% CI 0.2 to 0.8) were identified. For 2375 women who were reported to have received folic acid but not until later in the pregnancy (n = 1825) or not at all (n = 550), there were 53 outcomes with an MCM (2.2%; 95% CI 1.7 to 2.9) and eight NTDs (0.34%; 95% CI 0.2 to 0.7).
Conclusions: The study supports the view that extrapolation from studies carried out in the general population to groups of women with epilepsy may be questionable. It may be that the increased risk of MCM recorded in this group occurs through mechanisms other than that of folic acid metabolism.
See Editorial Commentary, p 468
Funding: We are grateful to the Epilepsy Research Foundation and Epilepsy Action for their support of this project. The study was made possible by a research grant from the Epilepsy Research Foundation and a number of educational grants from pharmaceutical companies (Eisai, Glaxo-Smith-Kline, Janssen-Cilag, Pfizer, Sanofi-Aventis and UCB-Pharma). An internet based website detailing the aims of the UK Epilepsy and Pregnancy Register was made possible by a grant from Glaxo-Smith-Kline and UCB-Pharma.
Competing interests: JIM, SJH, AJR, WHS, LP, PJM, RW, BI and JJC have attended meetings with the support of various pharmaceutical companies, including Eisai, Glaxo-Smith-Kline, Janssen-Cilag, Pfizer, Sanofi-Aventis and UCB-Pharma. JJC, LP, PJM and JIM have given lectures at the bequest of pharmaceutical companies for which they have received honoraria. IR reports no conflicts of interest.
Ethics approval: Ethics approval was obtained from the North Thames multicentre research ethics committee and subsequently from all UK local research ethics committees.