Posts Tagged women with epilepsy

[Abstract + References] Therapeutic Drug Monitoring of Antiepileptic Drugs in Women with Epilepsy Before, During, and After Pregnancy – Review

Abstract

During pregnancy, the pharmacokinetics of an antiepileptic drug is altered because of changes in the clearance capacity and volume of distribution. These changes may have consequences for the frequency of seizures during pregnancy and fetal exposure to antiepileptic drugs. In 2009, a review was published providing guidance for the dosing and therapeutic drug monitoring of antiepileptic drugs during pregnancy. Since that review, new drugs have been licensed and new information about existing drugs has been published. With this review, we aim to provide an updated narrative overview of changes in the pharmacokinetics of antiepileptic drugs in women during pregnancy. In addition, we aim to formulate advice for dose modification and therapeutic drug monitoring of antiepileptic drugs. We searched PubMed and the available literature on the pharmacokinetic changes of antiepileptic drugs and seizure frequency during pregnancy published between January 2007 and September 2018. During pregnancy, an increase in clearance and a decrease in the concentrations of lamotrigine, levetiracetam, oxcarbazepine’s active metabolite licarbazepine, topiramate, and zonisamide were observed. Carbamazepine clearance remains unchanged during pregnancy. There is inadequate or no evidence for changes in the clearance or concentrations of clobazam and its active metabolite N-desmethylclobazam, gabapentin, lacosamide, perampanel, and valproate. Postpartum elimination rates of lamotrigine, levetiracetam, and licarbazepine resumed to pre-pregnancy values within the first few weeks after pregnancy. We advise monitoring of antiepileptic drug trough concentrations twice before pregnancy. This is the reference concentration. We also advise to consider dose adjustments guided by therapeutic drug monitoring during pregnancy if the antiepileptic drug concentration decreases 15–25% from the pre-pregnancy reference concentration, in the presence of risk factors for convulsions. If the antiepileptic drug concentration changes more than 25% compared with the reference concentration, dose adjustment is advised. Monitoring of levetiracetam, licarbazepine, lamotrigine, and topiramate is recommended during and after pregnancy. Monitoring of clobazam, N-desmethylclobazam, gabapentin, lacosamide, perampanel, and zonisamide during and after pregnancy should be considered. Because of the risk of teratogenic effects, valproate should be avoided during pregnancy. If that is impossible, monitoring of both total and unbound valproate is recommended. More research is needed on the large number of unclear pregnancy-related effects on the pharmacokinetics of antiepileptic drugs.

References

  1. 1.

    Meador KJ, Baker GA, Browning N, et al. Effects of fetal antiepileptic drug exposure: outcomes at age 4.5 years. Neurology. 2012;78:1207–14.

  2. 2.

    Teramo K, Hiilesmaa V. Pregnancy and fetal complications in epileptic pregnancies. In: Janz D, Dam M, Bossi L, Helge H, Richens A, Schmidt D, editors. Epilepsy, pregnancy, child. New York: Raven Press; 1982. p. 53–9.

  3. 3.

    Harden CL, Pennell PB, Koppel BS, et al. Practice parameter update: management issues for women with epilepsy—focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding. Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology. 2009;73:142–9.

  4. 4.

    Voinescu PE, Park S, Chen LQ, et al. Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy. Neurology. 2018;91(13):e1228–36. https://doi.org/10.1212/WNL.0000000000006240.

  5. 5.

    Tomson T, Landmark CJ, Battino D. Antiepileptic drug treatment in pregnancy: changes in drug disposition and their clinical implications. Epilepsia. 2013;54:405–14.

  6. 6.

    Patsalos PN, Berry DJ, Bourgeois BF, et al. Antiepileptic drugs: best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia. 2008;49:1239–76.

  7. 7.

    Tomson T, Battino D, Bonizzoni E, et al. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. Lancet Neurol. 2011;10:609–17.

  8. 8.

    Tomson T, Battino D, Bonizzoni E, et al. Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry. Lancet Neurol. 2018;17:530–8.

  9. 9.

    Briggs GG, Freeman RK, Towers CV. Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. Philadelphia: Lippincott Williams and Wilkins; 2017.

  10. 10.

    Campbell E, Kennedy F, Russell A. Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers. J Neurol Neurosurg Psychiatry. 2014;85:1029–34.

  11. 11.

    Holmes L, Harvey E, Coull B. The teratogenicity of anticonvulsant drugs. N Engl J Med. 2001;344:1132–8.

  12. 12.

    Güveli BT, Rosti RO, Güzeltas A, et al. Teratogenicity of antiepileptic drugs. Clin Psychopharmacol Neurosci. 2017;15:19–27.

  13. 13.

    Meador KJ, Baker GA, Browning N, et al. Foetal antiepileptic drug exposure and verbal versus non-verbal abilities at three years of age. Brain. 2011;134:396–404.

  14. 14.

    uptodate.com. Available from: https://www.uptodate.com/contents/search. Accessed 21 June 2018.

  15. 15.

    Johnson EL, Stowe ZN, Ritchie JC, et al. Carbamazepine clearance and seizure stability during pregnancy. Epilepsy Behav. 2014;33:49–53.

  16. 16.

    Reisinger TL, Newman M, Loring DW, et al. Antiepileptic drug clearance and seizure frequency during pregnancy in women with epilepsy. Epilepsy Behav. 2013;29:13–8.

  17. 17.

    Battino D, Tomson T, Bonizzoni E, et al. Seizure control and treatment changes in pregnancy: observations from the EURAP epilepsy pregnancy registry. Epilepsia. 2013;54:1621–7.

  18. 18.

    Thomas S, Syan U, Devi J. Predictors of seizures during pregnancy in women with epilepsy. Epilepsia. 2012;53:2010–3.

  19. 19.

    Öhman I, Sabers A, de Flon P, et al. Pharmacokinetics of topiramate during pregnancy. Epilepsy Res. 2009;87:124–9.

  20. 20.

    Patsalos PN, Gougoulaki M, Sander JW. Perampanel serum concentrations in adults with epilepsy: effect of dose, age, sex and concomitant anti-epileptic drugs. Ther Drug Monit. 2016;38:358–64.

  21. 21.

    López-Fraile IP, Cid AO, Juste AO, et al. Levetiracetam plasma level monitoring during pregnancy, delivery, and postpartum: clinical and outcome implications. Epilepsy Behav. 2009;15:372–5.

  22. 22.

    Sabers A, Buchholt J, Uldall P, et al. Lamotrigine plasma levels reduced by oral contraceptives. Epilepsy Res. 2001;47:151–4.

  23. 23.

    Sabers A, Ohman I, Christensen J, et al. Oral contraceptives reduce lamotrigine plasma levels. Neurology. 2003;61:570–1.

  24. 24.

    Vajda F, O’Brien T, Lander C, et al. The efficacy of the newer antiepileptic drugs in controlling seizures in pregnancy. Epilepsia. 2014;55:1229–34.

  25. 25.

    Öhman I, Beck O, Vitols S. Plasma concentrations of lamotrigine and its 2-N-glucuronide metabolite during pregnancy in women with epilepsy. Epilepsia. 2008;49:1075–80.

  26. 26.

    Pennell PB, Peng L, Newport DJ, et al. Lamotrigine in pregnancy: clearance, therapeutic drug monitoring, and seizure frequency. Neurology. 2008;70:2130–6.

  27. 27.

    Wegner I, Edelbroek P, De Haan GJ, et al. Drug monitoring of lamotrigine and oxcarbazepine combination during pregnancy. Epilepsia. 2010;51:2500–2.

  28. 28.

    Sabers A, Petrenaite V. Seizure frequency in pregnant women treated with lamotrigine monotherapy. Epilepsia. 2009;50:2163–6.

  29. 29.

    Reimers A, Brodtkorb E. Second-generation antiepileptic drugs and pregnancy: a guide for clinicians. Expert Rev Neurother. 2012;12:707–17.

  30. 30.

    Polepally AR, Pennell PB, Brundage RC, et al. Model-based lamotrigine clearance changes during pregnancy: clinical implication. Ann Clin Transl Neurol. 2014;1:99–106.

  31. 31.

    Fotopoulou C, Kretz R, Bauer S, et al. Prospectively assessed changes in lamotrigine-concentration in women with epilepsy during pregnancy, lactation and the neonatal period. Epilepsy Res. 2009;85:60–4.

  32. 32.

    Tomson T, Battino D. Pharmacokinetics and therapeutic drug monitoring of newer antiepileptic drugs during pregnancy and the puerperium. Clin Pharmacokinet. 2007;46:209–19.

  33. 33.

    Novy J, Hubschmid M, Michel P, et al. Impending status epilepticus and anxiety in a pregnant woman treated with levetiracetam. Epilepsy Behav. 2008;13:564–6.

  34. 34.

    Westin A, Reimers A, Helde G, et al. Serum concentration/dose ratio of levetiracetam before, during and after pregnancy. Seizure. 2008;17:192–8.

  35. 35.

    Garrity LC, Turner M, Standridge SM. Increased levetiracetam clearance associated with a breakthrough seizure in a pregnant patient receiving once/day extended-release levetiracetam. Pharmacotherapy. 2014;34:e128–32.

  36. 36.

    Cappellari AM, Cattaneo D, Clementi E, et al. Increased levetiracetam clearance and breakthrough seizure in a pregnant patient successfully handled by intensive therapeutic drug monitoring. Ther Drug Monit. 2015;37:285–7.

  37. 37.

    Tomson T, Palm R, Källén K, et al. Pharmacokinetics of levetiracetam during pregnancy, delivery, in the neonatal period, and lactation. Epilepsia. 2007;48:1111–6.

  38. 38.

    Petrenaite V, Sabers A, Hansen-Schwartz J. Seizure deterioration in women treated with oxcarbazepine during pregnancy. Epilepsy Res. 2009;84:245–9.

  39. 39.

    Westin AA, Nakken KO, Johannessen SI, et al. Serum concentration/dose ratio of topiramate during pregnancy. Epilepsia. 2009;50:480–5.

  40. 40.

    Ornoy A, Zvi N, Arnon J, et al. The outcome of pregnancy following topiramate treatment: a study on 52 pregnancies. Reprod Toxicol. 2008;25:388–9.

  41. 41.

    Johannessen Landmark C, Huuse Farmen A, Larsen Burns M, et al. Pharmacokinetic variability of valproate during pregnany: implications for the use of therapeutic drug monitoring. Epilepsy Res. 2018;141:31–7.

  42. 42.

    Reimers A, Helde G, Becser Andersen N, et al. Zonisamide serum concentrations during pregnancy. Epilepsy Res. 2018;144:25–9.

  43. 43.

    Oles KS, Bell WL. Zonisamide concentrations during pregnancy. Ann Pharmacother. 2008;42:1139–41.

  44. 44.

    Anderson GD. Pregnancy-induced changes in pharmacokinetics: a mechanistic-based approach. Clin Pharmacokinet. 2005;44:989–1008.

  45. 45.

    Wegner I, Edelbroek P, Bulk S, et al. Lamotrigine kinetics within the menstrual cycle, after menopause, and with oral contraceptives. Neurology. 2009;73:1388–93.

  46. 46.

    Herzog AG, Blum AS, Farina EL, et al. Valproate and lamotrigine level variation with menstrual cycle phase and oral contraceptive use. Neurology. 2009;72:911–4.

  47. 47.

    Thangaratinam S, Marlin N, Newton S, et al. AntiEpileptic drug Monitoring in PREgnancy (EMPiRE): a double-blind randomised trial on effectiveness and acceptability of monitoring strategies. Health Technol Assess. 2018;22:1–152.

  48. 48.

    FDA, CDER, CVM. Bioanalytical method validation guidance for industry. Silver Spring: Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER) and Center for Veterinary Medicine (CVM); 2018.

  49. 49.

    EMA. Guideline on bioanalytical method validation. Eur Med Agency Comm Med Prod Hum Use. 2015;44:1–23.

  50. 50.

    Art. 3 van het Besluit Geneesmiddelenwet. 2018. Available from: http://wetten.overheid.nl/BWBR0021672/2018-01-01#Paragraaf2. Accessed 22 Nov 2019.

  51. 51.

    Sabers A. Algorithm for lamotrigine dose adjustment before, during, and after pregnancy. Acta Neurol Scand. 2012;126:e1–4.

  52. 52.

    European Medicines Agency. New measures to avoid valproate exposure in pregnancy endorsed. London: European Medicines Agency (EMA); 2018. p. 1–4.

  53. 53.

    International League Against Epilepsy (ILAE) and European Academy of Neurology (EAN). Valproate in the treatment of epilepsy in women and girls. Pre-publication summary of recommendations from a joint Task Force of ILAE-Commission on European Affairs and European Academy of Neurology (EAN). 2018. Available from: https://www.ilae.org/files/ilaeGuideline/ValproateCommentILAE-0315.pdf. Accessed 22 Nov 2019.

  54. 54.

    Hernandez-Diaz S, Smith C, Shen A. Comparative safety of antiepileptic drugs during pregnancy. Neurology. 2012;78:1692–9.

  55. 55.

    Patsalos PN, Zugman M, Lake C, et al. Serum protein binding of 25 antiepileptic drugs in a routine clinical setting: a comparison of free non-protein-bound concentrations. Epilepsia. 2017;58:1234–43.

  56. 56.

    Kacirova I, Grundmann M, Brozmanova H. Concentrations of carbamazepine and carbamazepine-10,11-epoxide in maternal and umbilical cord blood at birth: influence of co-administration of valproic acid or enzyme-inducing antiepileptic drugs. Epilepsy Res. 2016;122:84–90.

  57. 57.

    de Leon J, Spina E, Diaz FJ. Clobazam therapeutic drug monitoring: a comprehensive review of the literature with proposals to improve future studies. Ther Drug Monit. 2013;35:30–47.

  58. 58.

    Burns M, Baftiu A, Opdal M, et al. Therapeutic drug monitoring of clobazam and its metabolite: impact of age and comedication on pharmacokinetic variability. Ther Drug Monit. 2016;38:350–7.

  59. 59.

    Shorvon S, Perucca E, Engel J Jr. The treatment of epilepsy. 4th ed. Chichester: Wiley; 2016.

  60. 60.

    Kacirova I, Grundmann M, Brozmanova H. Serum levels of lamotrigine during delivery in mothers and their infants. Epilepsy Res. 2010;91:161–5.

  61. 61.

    Lyseng-Williamson K, Yang L. Spotlight on topiramate in epilepsy. CNS Drugs. 2008;22:171–4.

  62. 62.

    Sills G, Brodie M. Pharmacokinetics and drug interactions with zonisamide. Epilepsia. 2007;48:435–41.

  63. 63.

    Kawada K, Itoh S, Kusaka T, et al. Pharmacokinetics of zonisamide in perinatal period. Brain Dev. 2002;24:95–7.

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[Abstract] Do Women with epilepsy benefit from epilepsy specific pre-conception care?

Abstract

BACKGROUND

To determine how pre-conception care (PCC) influenced the outcome of epilepsy, pregnancy and malformation risk in women with epilepsy (WWE)

METHODS

All primigravida in the Kerala registry of epilepsy and pregnancy (KREP) with the final outcome of pregnancy known who were enrolled prospectively in pre-conception stage (PCC group) or first trimester of pregnancy (PRG group) were included. The two groups were compared for fetal and maternal outcomes including seizure control and complications of pregnancy.

RESULTS

There were 320 (30.4%) in PCC group and 732 in PRG group. Both groups were comparable for epilepsy classification, maternal birth defects and family history of epilepsy but the PCC group had significantly higher education (48.9%, p = .027) and employment (22.1%, p < .001). They had higher usage of folate in pre-pregnancy month (87.5%, p < .001) and first trimester (96.3%, p < .001) than PRG group. Fewer women in the PCC group were off AEDs in first trimester (5% vs 9.3%, p = .018). Within monotherapy group, use of levetiracetam (10.8%, p = .017), valproate ( 34%, p = .002) in PCC group and carbamazepine (39.1%, p = .04), phenobarbitone (13.3%, p = .001) in PRG group was significantly high. More women in this group were seizure free during pregnancy (62.8%, p = .005) than PRG group. Early fetal loss was better captured in PCC (90.6%,p = .025) than in the PRG. There was no difference in malformation rate between PCC (7.2%) and PRG groups (6.1%, p = .3).

CONCLUSION

PCC reduced the risk of seizures during pregnancy and improved the periconceptional use of folate but did not influence the fetal malformation risk.

 

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[Abstract + References] The impact of maternal epilepsy on delivery and neonatal outcomes

Abstract

Purpose

Epilepsy is a common neurological disorder that may complicate reproductive health. Our aim in this study was to provide prospective ascertainment of obstetric and neonatal outcomes in women with epilepsy and investigate whether the risk of pregnancy, delivery, and neonatal complications differed between women with epilepsy and women without epilepsy.

Methods

Pregnant women with epilepsy and women without epilepsy (control group) were prospectively evaluated during the years 2013–2018. They were regularly followed by a neurologist and obstetrician until the end of pregnancy.

Results

Delivery and perinatal outcomes were compared between 112 women diagnosed with epilepsy and 277 women without epilepsy. Epilepsy was a significant risk factor for preterm delivery, cesarean section, fetal hypoxia, and Apgar score ≤ 7 at 5 min in offspring (odds ratio (OR) = 2.83, 95% confidence interval (CI) 1.03–7.76; OR = 5.61, 95% CI 3.44–9.14; OR = 1.81, 95% CI 1.08–3.04; OR = 8.12, 95% CI 4.04–16.35, respectively). Seizures during pregnancy had influence on the preference of cesarean section as a mode of delivery (ОR = 3.39; 95% CI 1.40–8.17). The rate of perinatal hypoxia was significantly higher in children born by cesarean section (ОR = 2.84; 95% CI 1.04–7.76). There was no significant difference between women with epilepsy and controls in malformation rate.

Conclusions

Women with epilepsy had an increased risk of pregnancy and delivery complications. Cesarean section was associated with an increased risk of complications in offspring.

 

References

  1. 1.
    Harden C (2008) Antiepileptic drug teratogenesis: what are the risks for congenital malformations and adverse cognitive outcomes? Int Rev Neurobiol 83:205–213.  https://doi.org/10.1016/S0074-7742(08)00011-1CrossRefPubMedGoogle Scholar
  2. 2.
    Bromley R, Baker G (2017) Fetal antiepileptic drug exposure and cognitive outcomes. Seizure 44:225–231.  https://doi.org/10.1016/j.seizure.2016.10.006CrossRefPubMedGoogle Scholar
  3. 3.
    Leach J, Smith P, Craig J, Bagary M, Cavanagh D, Duncan S et al (2017) Epilepsy and pregnancy: for healthy pregnancies and happy outcomes. Suggestions for service improvements from the Multispecialty UK Epilepsy Mortality Group. Seizure 50:67–72.  https://doi.org/10.1016/j.seizure.2017.05.004CrossRefPubMedGoogle Scholar
  4. 4.
    Borthen I, Eide M, Veiby G, Daltveit A, Gilhus N (2009) Complications during pregnancy in women with epilepsy: population-based cohort study. BJOG 116(13):1736–1742.  https://doi.org/10.1111/j.1471-0528.2009.02354.xCrossRefPubMedGoogle Scholar
  5. 5.
    Artama M, Braumann J, Raitanen J, Uotila J, Gissler M, Isojärvi J et al (2017) Women treated for epilepsy during pregnancy: outcomes from a nationwide population-based cohort study. Acta Obstet Gynaecol Scand 96(7):812–820.  https://doi.org/10.1111/aogs.13109CrossRefGoogle Scholar
  6. 6.
    Borthen I, Eide M, Daltveit A, Gilhus N (2010) Delivery outcome of women with epilepsy: a population-based cohort study. BJOG 117:1537–1543.  https://doi.org/10.1111/j.1471-0528.2010.02694.xCrossRefPubMedGoogle Scholar
  7. 7.
    Borthen I (2015) Obstetrical complications in women with epilepsy. Seizure 28:32–34.  https://doi.org/10.1016/j.seizure.2015.02.018CrossRefPubMedGoogle Scholar
  8. 8.
    Sveberg L, Svalheim S, Taubøll E (2015) The impact of seizures on pregnancy and delivery. Seizure 28:35–38.  https://doi.org/10.1016/j.seizure.2015.02.020CrossRefPubMedGoogle Scholar
  9. 9.
    Razaz N, Tomson T, Wikström A, Cnattingius S (2017) Association between pregnancy and perinatal outcomes among women with epilepsy. JAMA Neurol 74(8):983–991.  https://doi.org/10.1001/jamaneurol.2017.1310CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Hiilesmaa V, Bardy A, Teramo K (1985) Obstetric outcome in women with epilepsy. Am J Obstet Gynecol 152(5):499–504CrossRefGoogle Scholar
  11. 11.
    Viinikainen K, Heinonen S, Eriksson K, Kälviäinen R (2006) Community-based, prospective, controlled study of obstetric and neonatal outcome of 179 pregnancies in women with epilepsy. Epilepsia 47:186–192.  https://doi.org/10.1111/j.1528-1167.2006.00386.xCrossRefPubMedGoogle Scholar
  12. 12.
    Richmond J, Krishnamoorthy P, Andermann E, Benjamin A (2004) Epilepsy and pregnancy: an obstetric perspective. Am J Obstet Gynecol 190(2):371–379CrossRefGoogle Scholar
  13. 13.
    Pilo C, Wide K, Winbladh B (2006) Pregnancy, delivery, and neonatal complications after treatment with antiepileptic drugs. Acta Obstet Gynecol Scand 85:643–646.  https://doi.org/10.1080/00016340600604625CrossRefPubMedGoogle Scholar
  14. 14.
    Thomas S, Sindhu K, Ajaykumar B, Sulekha D, Sujamol J (2009) Maternal and obstetric outcome on in women with epilepsy. Seizure 18(3):163–166.  https://doi.org/10.1016/j.seizure.2008.08.010CrossRefPubMedGoogle Scholar
  15. 15.
    Hvas C, Henriksen T, Оstergaard J, Mogens D (2000) Epilepsy and pregnancy: effect of antiepileptic drugs and lifestyle on birthweight. Br J Obstet Gynaecol 107:896–902CrossRefGoogle Scholar
  16. 16.
    Yerby MS (2000) Quality of life, epilepsy advances, and the evolving role of anticonvulsants in women with epilepsy. Neurology 55(5 Suppl 1):21–31 discussion S 54-8Google Scholar
  17. 17.
    Tomson T, Battino D, Bonizzoni E, Craig J, Lindhout D, Perucca E, Sabers A, Thomas SV, Vajda F, EURAP Study Group (2015) Antiepileptic drugs and intrauterine death: a prospective observational study from EURAP. Neurology 85(7):580–588.  https://doi.org/10.1212/WNL.0000000000001840CrossRefPubMedGoogle Scholar
  18. 18.
    Kasradze S, Gogatishvili N, Lomidze G, Ediberidze T, Lazariashvili M, Khomeriki K, Mamukadze S, Metreveli M, Gagoshidze T, Tatishvili N, Tomson T (2017) Cognitive functions in children exposed to antiepileptic drugs in utero – study in Georgia. Epilepsy Behav 66:105–112.  https://doi.org/10.1016/j.yebeh.2016.10.014CrossRefPubMedGoogle Scholar
  19. 19.
    Katz O, Levy A, Wiznitzer A, Sheiner E (2006) Pregnancy and perinatal outcome in epileptic women: a population-based study. J Matern Fetal Neonatal Med 19(1):21–25.  https://doi.org/10.1080/14767050500434096CrossRefPubMedGoogle Scholar
  20. 20.
    Shahla M, Hijran B, Sharif M (2018) The course of epilepsy and seizure control in pregnant women. Acta Neurol Belg 118:459–464.  https://doi.org/10.1007/s13760-018-0974-0CrossRefPubMedGoogle Scholar
  21. 21.
    Thomas S, Syam U, Devy J (2012) Predictors of seizures during pregnancy in women with epilepsy. Epilepsia 53(5):e85–e88.  https://doi.org/10.1111/j.1528-1167.2012.03439.xCrossRefGoogle Scholar
  22. 22.
    Ozdemir O, Mustafa E, Aslihan K, Selimova V, Atalay C (2015) Pregnancy outcome of 149 pregnancies in women with epilepsy: experience from a tertiary care hospital. Interv Med Appl Sci 7(3):108–113.  https://doi.org/10.1556/1646.7.2015.3.4CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Vajda F, O’Brien T, Graham J, Hitchcock A, Lander C, Eadie M (2018) Predicting epileptic seizure control during pregnancy. Epilepsy Behav 78:91–95.  https://doi.org/10.1016/j.yebeh.2017.10.017CrossRefPubMedGoogle Scholar
  24. 24.
    Soontornpun A, Choovanichvong T, Tongsong T (2018) Pregnancy outcomes among women with epilepsy: a retrospective cohort study. Epilepsy Behav 82:52–56.  https://doi.org/10.1016/j.yebeh.2018.03.001CrossRefPubMedGoogle Scholar
  25. 25.
    Borthen I, Eide M, Daltveit A, Gilhus N (2011) Obstetric outcome in women with epilepsy: a hospital-based, retrospective study. BJOG 118(8):956–965.  https://doi.org/10.1111/j.1471-0528.2011.03004.xCrossRefPubMedGoogle Scholar
  26. 26.
    Viale L, Allotey J, Cheong-See F, Arroyo-Manzano D, Mccorry D, Bagary M, EBM CONNECT Collaboration et al (2015) Epilepsy in pregnancy and reproductive outcomes: a systematic review and meta-analysis. Lancet 386(10006):1845–1852.  https://doi.org/10.1016/S0140-6736(15)00045-8CrossRefPubMedGoogle Scholar
  27. 27.
    Kusznir Vitturi B, Barreto Cabral F, Mella Cukiert C (2019) Outcomes of pregnant women with refractory epilepsy. Seizure 69:251–257CrossRefGoogle Scholar
  28. 28.
    MacDonald S, Bateman B, McElrath T, Hernández-Díaz S (2015) Mortality and morbidity during delivery hospitalization among pregnant women with epilepsy in the United States. JAMA Neurol 72(9):981–988.  https://doi.org/10.1001/jamaneurol.2015.1017CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Vajda F, O’Brien T, Graham J, Hitchcock A, Kuhn Viale L, Allotey JR, Lander C, Eadie M (2018) Cesarean section in Australian women with epilepsy. Epilepsy Behav 89:126–129.  https://doi.org/10.1016/j.yebeh.2018.10.008CrossRefPubMedGoogle Scholar
  30. 30.
    Veiby G, Daltveit A, Engelsen B, Gilhus N (2009) Pregnancy, delivery, and outcome for the child in maternal epilepsy. Epilepsia 50(9):2130–2139.  https://doi.org/10.1111/j.1528-1167.2009.02147.xCrossRefPubMedGoogle Scholar
  31. 31.
    Tollanes M (2009) Increased rate of caesarean sections – causes and consequences. Tidsskr Nor Legeforen 129:1329–1331.  https://doi.org/10.4045/tidsskr.08.0453CrossRefGoogle Scholar
  32. 32.
    Kolas T, Hofoss D, Daltveit A, Nilsen S, Henriksen T, Häger R et al (2003) Indications for cesarean deliveries in Norway. Am J Obstet Gynecol 188:864–870CrossRefGoogle Scholar
  33. 33.
    Othman N, Rahman A (2013) Obstetric and birth outcomes in pregnant women with epilepsy: a hospital-based study. Ann Indian Acad Neurol 16:534–537.  https://doi.org/10.4103/0972-2327.120458CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Chen Y, Chiou H, Lin H, Lin H (2009) Affect of seizures during gestation on pregnancy outcomes in women with epilepsy. Arch Neurol 66(8):979–984.  https://doi.org/10.1001/archneurol.2009.142CrossRefPubMedGoogle Scholar
  35. 35.
    Christensen J, Pedersen H, Kjaersgaard M, Parner E, Vestergaard M, Sørensenet M et al (2015) Apgar-score in children prenatally exposed to antiepileptic drugs: a population-based cohort study. BMJ Open 5:e007425.  https://doi.org/10.1136/bmjopen-2014-007425CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Farmen A, Grundt J, Nakling J, Mowinckel P, Nakken K, Lossius M (2019) Increased rate of acute caesarean sections in women with epilepsy: results from the Oppland Perinatal Database in Norway. Eur J Neurol 26(4):617–623.  https://doi.org/10.1111/ene.13865CrossRefPubMedGoogle Scholar
  37. 37.
    Liporace J, D’Abreu A (2003) Epilepsy and women’s health: family planning, bone health, menopause, and menstrual-related seizures. Mayo Clin Proc78 78:497–506CrossRefGoogle Scholar
  38. 38.
    Rauchenzauner M, Ehrensberger M, Prieschl M, Kapelari K, Bergmann M, Walser G, Neururer S, Unterberger I, Luef G (2013) Generalized tonic-clonic seizures and antiepileptic drugs during pregnancy – a matter of importance for the baby? J Neurol 260:484–488.  https://doi.org/10.1007/s00415-012-6662-8CrossRefPubMedGoogle Scholar
  39. 39.
    Quiroz L, Chang H, Blomquist J, Okoh Y, Handa V (2008) Scheduled cesarean delivery: maternal and neonatal risks in primiparous women in a community hospital setting. Am J Perinatol 26(4):271–277.  https://doi.org/10.1055/s-0028-1103155CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Kamath B, Todd J, Glazner J, Lezotte D, Lynch A (2009) Neonatal outcomes after elective cesarean delivery. Obstet Gynecol 113(6):1231–1238.  https://doi.org/10.1097/AOG.0b013e3181a66d57ıCrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Pennell PB (2008) Antiepileptic drugs during pregnancy: what is known and which AEDs seem to be safest? Epilepsia 49(Suppl 9):43–55.  https://doi.org/10.1111/j.1528-1167.2008.01926.xCrossRefPubMedGoogle Scholar
  42. 42.
    Tomson T, Xue H, Battino D (2015) Major congenital malformations in children of women with epilepsy. Seizure 28:46–50.  https://doi.org/10.1016/j.seizure.2015.02.019CrossRefPubMedGoogle Scholar
  43. 43.
    Galappatthy P, Liyanage CK, Lucas MN et al (2018) Obstetric outcomes and effects on babies born to women treated for epilepsy during pregnancy in a resource limited setting: a comparative cohort study. BMC Pregnancy Childbirth 18(1):230.  https://doi.org/10.1186/s12884-018-1857-3CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Battino D, Tomson T, Bonizzon E, Craig J, Lindhout D, Sabers A et al (2013) Seizure control and treatment changes in pregnancy: observations from the EURAP epilepsy pregnancy registry. Epilepsia 54(9):1621–1627.  https://doi.org/10.1111/epi.12302CrossRefPubMedGoogle Scholar
  45. 45.
    Mawhinney E, Craig J, Morrow J, Russell A, Smithson W, Parsons L, Morrison PJ, Liggan B, Irwin B, Delanty N, Hunt SJ (2013) Levetiracetam in pregnancy: results from the UK and Ireland epilepsy and pregnancy registers. Neurology 80(4):400–405.  https://doi.org/10.1212/WNL.0b013e31827f0874CrossRefPubMedGoogle Scholar
  46. 46.
    Kazemi M, Salehi M, Kheirollahi M (2016) Down syndrome: current status, challenges and future perspectives. Int J Mol Cell Med 5(3):125–133PubMedPubMedCentralGoogle Scholar
  47. 47.
    Veiby G, Bjørk M, Engelsen B, Gilhus N (2015) Epilepsy and recommendations for breastfeeding. Seizure 28:57–65.  https://doi.org/10.1016/j.seizure.2015.02.013CrossRefPubMedGoogle Scholar
  48. 48.
    Stephen L, Harden C, Tomson T, Brodie M (2019) Management of epilepsy in women. Lancet Neurol 18(5):481–491.  https://doi.org/10.1016/S1474-4422(18)30495-2CrossRefPubMedGoogle Scholar
  49. 49.
    He S, Zhu H, Qiu X, Zhu X, Peng A, Duan J, Chen L (2017) Pregnancy outcome in women with epilepsy in Western China: a prospective hospital based study. Epilepsy Behav 74:10–14.  https://doi.org/10.1016/j.yebeh.2017.05.034CrossRefPubMedGoogle Scholar
  50. 50.
    Johnson E, Burke A, Wang A, Pennell P (2018) Unintended pregnancy, prenatal care, newborn outcomes, and breastfeeding in women with epilepsy. Neurology 91(11):e1031–e1039.  https://doi.org/10.1212/WNL.0000000000006173CrossRefPubMedGoogle Scholar

via The impact of maternal epilepsy on delivery and neonatal outcomes | SpringerLink

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[ARTICLE] Maternal complications in pregnancy and childbirth for women with epilepsy: Time trends in a nationwide cohort – Full Text

Abstract

Objective

Obstetric trends show changes in complication rates and maternal characteristics such as caesarean section, induced labour, and maternal age. To what degree such general time trends and changing patterns of antiepileptic drug use influence pregnancies of women with epilepsy (WWE) is unknown. Our aim was to describe changes in maternal characteristics and obstetric complications in WWE over time, and to assess changes in complication risks in WWE relative to women without epilepsy.

Methods

This was a nationwide cohort study of all first births in the Medical Birth Registry of Norway, 1999–2016. We estimated maternal characteristics, complication rates, and risks for WWE compared to women without epilepsy. Main maternal outcome measures were hypertensive disorders, bleeding in pregnancy, induction of labour, caesarean section, postpartum hemorrhage, preterm birth, small for gestational age, and epidural analgesia. Time trends were analyzed by logistic regression and comparisons made with interaction analyses.

Results

426 347 first births were analyzed, and 3077 (0.7%) women had epilepsy. In WWE there was an increase in proportions of induced labour (p<0.005) and use of epidural analgesia (p<0.005), and a reduction in mild preeclampsia (p = 0.006). However, the risk of these outcomes did not change over time. Only the risk of severe preeclampsia increased significantly over time relative to women without epilepsy (p = 0.006). In WWE, folic acid supplementation increased significantly over time (p<0.005), and there was a decrease in smoking during pregnancy (p<0.005), but these changes were less pronounced than for women without epilepsy (p<0.005).

Conclusions

During 1999–2016 there were important changes in maternal characteristics and complication rates among WWE. However, outcome risks for WWE relative to women without epilepsy did not change despite changes in antiepileptic drug use patterns. The relative risk of severe preeclampsia increased in women with epilepsy.

Introduction

Epilepsy is one of the most common chronic diseases during pregnancy.[14] Women with epilepsy (WWE) have been considered as high risk parturients with increased risk for maternal complications.[28] Almost half of women with ongoing or previous epilepsy use antiepileptic drugs (AEDs) in pregnancy to control seizures despite their potential adverse effects on the fetus and maternal complications.[2911] The pattern of antiepileptic drug use in pregnant WWE has changed markedly during the last two decades owing to newer antiepileptic drugs, primarily lamotrigine and levetiracetam, replacing older antiepileptic drugs, such as carbamazepine, phenytoin, and valproate. [1214] The newer antiepileptic drugs are better tolerated and believed to have less fetal and maternal adverse effects, but are associated with increased seizure risk during pregnancy.[10111519] Increasing maternal age, increasing maternal body mass index (BMI), and decrease in smoking during pregnancy over the last two decades should also affect WWE.[2023] These factors could be proportional or have a more complex interaction. Global trends show an increase in caesarean section rates and increased induction of labour.[2426] Such interventions are common in WWE.[24578] During the last decade, there has been an increasing focus on management of WWE during pregnancy and delivery and recent guidelines encourage close monitoring of pregnancies in WWE and strict indications for interventions.[252730] However, there is little data on how focused management and guidelines have affected maternal outcomes of WWE. A recent meta-analysis indicates a trend towards increasing rates of caesarean section and induction of labour in WWE.[31] However, different geographical populations with great variation in obstetric practice were compared to describe differences over time, and no reference populations were included. Therefore, it is not known how changes in population characteristics, obstetric practice and general complication rates have affected WWE. We expect that changes during the recent years in folate use, indications for operative interventions, and AEDs used have all influenced maternal complications in WWE during pregnancy and when giving birth.

By analyzing a stable nationwide cohort over 18 years, our aim was to describe changes in maternal characteristics and maternal complication rates in WWE over time, and to assess changes in complication risks relative to women without epilepsy. For changes in outcome risks in WWE over time, the influence of AED use and other specific factors were assessed.

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[Abstract] The use of antidepressant drugs in pregnant women with epilepsy: A study from the Australian Pregnancy Register

Summary

Objective

To study interactions between first‐trimester exposure to antidepressant drugs (ADDs) and antiepileptic drugs (AEDs), and a history of clinical depression and/or anxiety, on pregnancy outcomes and seizure control in pregnant women with epilepsy (WWE).

Methods

We examined data from the Australian Pregnancy Register of Antiepileptic Drugs in Pregnancy, collected from 1999 to 2016. The register is an observational, prospective database, from which this study retrospectively analyzed a cohort. Among the AED‐exposed outcomes, comparisons were made among 3 exposure groups: (1) pregnancy outcomes with first‐trimester exposure to ADDs; (2) outcomes with mothers diagnosed with depression and/or anxiety but who were not medicated with an ADD; and (3) those with mothers who were not diagnosed with depression and/or anxiety and were not medicating with ADD. Prevalence data was analyzed using Fisher’s exact test.

Results

A total of 2124 pregnancy outcomes were included in the analysis; 1954 outcomes were exposed to AEDs in utero, whereas 170 were unexposed. Within the group of WWE taking AEDs, there was no significant difference in the prevalence of malformations in infants who were additionally exposed to ADDs (10.2%, 95% confidence interval [CI] 3.9‐16.6), compared to individuals in the non–ADD‐medicated depression and/or anxiety group (7.7%, 95% CI 1.2‐14.2), or those without depression or anxiety (6.9%, 95% CI 5.7‐8.1; = 0.45). The malformation rates in pregnancy outcomes unexposed to AEDs were also similar in the above groups (= 0.27). In WWE medicated with AEDs and ADDs, the frequency of convulsive seizures (= 0.78), or nonconvulsive seizures (= 0.45) throughout pregnancy, did not differ across comparative groups.

Significance

Co‐medicating with ADDs in WWE taking AEDs does not appear to confer a significant added teratogenic risk, and it does not affect seizure control.

 

via The use of antidepressant drugs in pregnant women with epilepsy: A study from the Australian Pregnancy Register – Sivathamboo – – Epilepsia – Wiley Online Library

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