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Folic acid use and major congenital malformations in offspring of women with epilepsy. A prospective study from the UK Epilepsy and Pregnancy Register.
  1. James I Morrow (jim.morrow{at}belfasttrust.hscni.net)
  1. Department of Neurology, The Royal Group of Hospitals, Belfast, United Kingdom
    1. Stephen J Hunt (stephen.hunt{at}belfasttrust.hscni.net)
    1. Department of Neurology, The Royal Group of Hospitals, Belfast, United Kingdom
      1. Aline J Russell (aline{at}neurophysiology.sgh.scot.nhs.uk)
      1. Department of Neurophysiology, Southern General Hospital, Glasgow, United Kingdom
        1. W Henry Smithson (henry.smithson{at}sypctgp.nhs.uk)
        1. The Surgery, Escrick, York, United Kingdom
          1. Linda Parsons (linda.parsons{at}whht.nhs.uk)
          1. Department of Neurology, St Albans City Hospital, St Albans, United Kingdom
            1. Iain Robertson (iain.robertson{at}lthtr.nhs.uk)
            1. Obstetrics and Gynaecology Department, Lancashire Teaching Hospitals NHS Trust, Sharoe Green Lane So, United Kingdom
              1. Ruth Waddell (ruth.waddell{at}belfasttrust.hscni.net)
              1. Department of Neurology, The Royal Group of Hospitals, Belfast, United Kingdom
                1. Beth Irwin (beth.irwin{at}belfasttrust.hscni.net)
                1. Department of Neurology, The Royal Group of Hospitals, Belfast, United Kingdom
                  1. Patrick J Morrison (patrick.morrison{at}belfasttrust.hscni.net)
                  1. Department of Medical Genetics, Belfast City Hospital Trust, Lisburn Road, Belfast, United Kingdom
                    1. John J Craig (john.craig{at}belfasttrust.hscni.net)
                    1. Department of Neurology, The Royal Group of Hospitals, Belfast, United Kingdom

                      Abstract

                      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 due to the known anti-folate effect of some anti-epileptic drugs (AEDs). Here we aim to determine 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 1,935 cases reported to have received pre-conceptual folic acid, 76 MCMs (3.9%; 95% C.I. 3.1 – 4.9%) and eight NTDs (0.4%; 95% C.I. 0.2 – 0.8) were identified. For 2,375 women who were reported to have received folic acid but not until later in the pregnancy (n= 1,825) or not at all (n=550) there were 53 outcomes with an MCM (2.2%; 95% C.I. 1.7 – 2.9%) and eight NTDs (0.34%; 95% C.I. 0.2 – 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.

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