暴露于新型抗癫痫发作药物后儿童神经发育结果的系统综述_Journal of Epilepsy

Authors：

 KnightR , WittkowskiA , BromleyRL , 刘晓慧　王婷　译 , 薛国芳　审

Corresponding author：

KnightR, Email: r.knight9591@gmail.com

Keywords：

抗癫痫发作药物; 儿童发育; 癫痫; 宫内; 拉莫三嗪; 妊娠

DOI：

10.7507/2096-0247.202206009

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由于孕期暴露于某些传统的抗癫痫发作药物（Anti-seizure medications，ASMs）与儿童较差的神经发育有关，因此在整个妊娠期间使用新型ASMs的情况有所增加。本研究旨在阐明子宫内暴露于这些新型ASMs对儿童神经发育的影响。对MEDLINE、Embase、Web of Science、Cumulative Index to Nursing and Allied Health Literature Plus和PsycINFO进行了系统检索，结果仅限于2000年后发表的英文文章。调查宫内暴露于新型ASMs后神经发育结果的研究，纳入评价的药物包括：艾司利卡西平、加巴喷丁、拉考沙胺、拉莫三嗪、左乙拉西坦、奥卡西平、吡仑帕奈、托吡酯和唑尼沙胺，最终确定了35份发表的相关研究，并进行了描述性整合。方法学质量不统一，其不同的优势/劣势归因于研究设计。大多数研究观察了暴露于拉莫三嗪后其对儿童神经发育的并没有显著影响。左乙拉西坦的高质量研究相对较少，迄今为止未得到结论。托吡酯、加巴喷丁和奥卡西平的数据非常有限，无法得出确切的结论。令人担忧的是，尚无关于艾司利卡西平、拉考沙胺、吡仑帕奈或唑尼沙胺的研究。到目前为止，暴露于某些新型ASMs（如拉莫三嗪和左乙拉西坦）似乎并未影响神经发育的特定方面，但需要在不同的神经发育方面和剂量水平上进行进一步的研究。由于缺乏数据，无法确定新型ASMs的安全性，这些尚待进一步研究。

Citation： KnightR, WittkowskiA, BromleyRL, 刘晓慧　王婷　译, 薛国芳　审. 暴露于新型抗癫痫发作药物后儿童神经发育结果的系统综述. Journal of Epilepsy, 2022, 8(6): 555-567. doi: 10.7507/2096-0247.202206009 Copy

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26.	Meador KJ, Baker GA, Browning N, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol, 2013, 12(3): 244-252.
27.	Veiby G, Engelsen BA, Gilhus NE. Early child development and exposure to antiepileptic drugs prenatally and through breastfeeding: a prospective cohort study on children of women with epilepsy. JAMA Neurol, 2013, 70(11): 1367-1374.
28.	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(2): 396-404.
29.	McVearry KM, Gaillard WD, VanMeter J, et al. A prospective study of cognitive fluency and originality in children exposed in utero to carbamazepine, lamotrigine, or valproate monotherapy. Epilepsy Behav, 2009, 16(4): 609-616.
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35.	Christensen J, Pedersen L, Sun YL, et al. Association of prenatal exposure to valproate and other antiepileptic drugs with risk for attention-deficit/hyperactivity disorder in offspring. JAMA Netw Open, 2019, 2(1): e186606.
36.	Christensen J, Grønborg TK, Sørensen MJ, et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA, 2013, 309(16): 1696-1703.
37.	Richards N, Reith D, Stitely M, et al. Developmental outcomes at age four following maternal antiepileptic drug use. Epilepsy Behav, 2019, 93: 73-79.
38.	Huber-Mollema Y, Oort FJ, Lindhout D, et al. Behavioral problems in children of mothers with epilepsy prenatally exposed to valproate, carbamazepine, lamotrigine, or levetiracetam monotherapy. Epilepsia, 2019, 60(6): 1069-1082.
39.	Lacey AS, Pickrell WO, Thomas RH, et al. Educational attainment of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry, 2018, 89(7): 736-740.
40.	Elkjær LS, Bech BH, Sun Y, et al. Association between prenatal valproate exposure and performance on standardized language and mathematics tests in school-aged children. JAMA Neurol, 2018, 75(6): 663-671.
41.	Deshmukh U, Adams J, Macklin EA, et al. Behavioral outcomes in children exposed prenatally to lamotrigine, valproate, or carbamazepine. Neurotoxicol Teratol, 2016, 54: 5-14.
42.	Shallcross R, Bromley RL, Irwin B, et al. Child development following in utero exposure: levetiracetam vs sodium valproate. Neurology, 2011, 76(4): 383-389.
43.	Shallcross R, Bromley RL, Cheyne CP, et al. In utero exposure to levetiracetam vs valproate: development and language at 3 years of age. Neurology, 2014, 82(3): 213-221.
44.	Guveli BT, Gurses C, Atakli D, et al. Behavioral characteristics and cognitive development among school age children born to women with epilepsy. Neurol Res, 2015, 37(4): 295-300.
45.	Rihtman T, Parush S, Ornoy A. Preliminary findings of the developmental effects of in utero exposure to topiramate. Reprod Toxicol, 2012, 34(3): 308-311.
46.	Adam MP, Polifka JE, Friedman JM. Evolving knowledge of the teratogenicity of medications in human pregnancy. Am J Med Genet C Semin Med Genet, 2011, 157C(3): 175-182.
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1. Weston J, Bromley R, Jackson CF, et al. Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. Cochrane Database Syst Rev, 2016, 11(11): CD010224.
2. Tomson T, Battino D, Perucca E. Teratogenicity of antiepileptic drugs. Curr Opin Neurol, 2019, 32(2): 246-252.
3. Bromley R, Weston J, Adab N, et al. Treatment for epilepsy in pregnancy: Neurodevelopmental outcomes in the child. Cochrane Database Syst Rev, 2014, 2014(10): CD010236.
4. Medications and Healthcare products Regulatory Agency. Valproate use in women and girls[EB/OL]. [2020-03-01].https:// www.gov.uk/guidance/valproate-use-by-women-and-girls.
5. Hill DS, Wlodarczyk BJ, Palacios AM, et al. Teratogenic effects of antiepileptic drugs. Expert Rev Neurother, 2010, 10(6): 943-959.
6. Meador KJ, Pennell PB, May RC, et al. Changes in antiepileptic drug-prescribing patterns in pregnant women with epilepsy. Epilepsy Behav, 2018, 84: 10-14.
7. Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (prisma-p) 2015 statement. Syst Rev, 2015, 4(1): 1.
8. Snilstveit B, Oliver S, Vojtkova M. Narrative approaches to systematic review and synthesis of evidence for international development policy and practice. J Dev Effect, 2012, 4(3): 409-429.
9. Egger M, Schneider M, Davey Smith G. Spurious precision? Meta-analysis of observational studies. BMJ, 1998, 316(7125): 140-144.
10. Wells GA, Shea B, O’Connell D, et al. Newcastle-Ottawa Scale (NOS) cohort studies[EB/OL]. [2020-03-01]. https://www.ncbi.nlm.nih.gov/books/NBK99082/bin/appb-fm4.pdf.
11. Bech L F, Polcwiartek C, Kragholm K, et al. In utero exposure to antiepileptic drugs is associated with learning disabilities among offspring. J Neurol Neurosurg Psychiatry, 2018, 89(12): 1324-1331.
12. Dean J C, Hailey H, Moore S J, et al. Long term health and neurodevelopment in children exposed to antiepileptic drugs before birth. J Med Genet, 2002, 39(4): 251-259.
13. Blotière PO, Miranda S, Weill A, et al. Risk of early neurodevelopmental outcomes associated with prenatal exposure to the antiepileptic drugs most commonly used during pregnancy: a French nationwide population-based cohort study. BMJ Open, 2020, 10(6): e034829.
14. Husebye ESN, Gilhus NE, Riedel B, et al. Verbal abilities in children of mothers with epilepsy: Association to maternal folate status. Neurology, 2018, 91(9): e811-e821.
15. Bjørk M, Riedel B, Spigset O, et al. Association of folic acid supplementation during pregnancy with the risk of autistic traits in children exposed to antiepileptic drugs in utero. JAMA Neurol, 2018, 75(2): 160-168.
16. Nadebaum C, Anderson V, Vajda F, et al. The Australian brain and cognition and antiepileptic drugs study: IQ in school-aged children exposed to sodium valproate and polytherapy. J Int Neuropsychol Soc, 2011, 17(1): 133-142.
17. Bromley RL, Mawer G, Love J, et al. Early cognitive development in children born to women with epilepsy: a prospective report. Epilepsia, 2010, 51(10): 2058-2065.
18. Baker GA, Bromley RL, Briggs M, et al. IQ at 6 years after in utero exposure to antiepileptic drugs: a controlled cohort study. Neurology, 2015, 84(4): 382-390.
19. Bromley RL, Calderbank R, Cheyne CP, et al. Cognition in school-age children exposed to levetiracetam, topiramate, or sodium valproate. Neurology, 2016, 87(18): 1943-1953.
20. Videman M, Stjerna S, Roivainen R, et al. Evidence for spared attention to faces in 7-month-old infants after prenatal exposure to antiepileptic drugs. Epilepsy Behav, 2016, 64 (Pt A): 62–68.
21. Cummings C, Stewart M, Stevenson M, et al. Neurodevelopment of children exposed in utero to lamotrigine, sodium valproate and carbamazepine. Arch Dis Child, 2011, 96(7): 643-647.
22. Rihtman T, Parush S, Ornoy A. Developmental outcomes at preschool age after fetal exposure to valproic acid and lamotrigine: cognitive, motor, sensory and behavioral function. Reprod Toxicol, 2013, 41: 115-125.
23. Huber-Mollema Y, van Iterson L, Oort FJ, et al. Neurocognition after prenatal levetiracetam, lamotrigine, carbamazepine or valproate exposure. J Neurol, 2020, 267(6): 1724-1736.
24. Kasradze S, Gogatishvili N, Lomidze G, et al. Cognitive functions in children exposed to antiepileptic drugs in utero—study in Georgia. Epilepsy Behav, 2017, 66: 105-112.
25. Meador KJ, Baker GA, Browning N, et al. Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. N Engl J Med, 2009, 360(16): 1597-1605.
26. Meador KJ, Baker GA, Browning N, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol, 2013, 12(3): 244-252.
27. Veiby G, Engelsen BA, Gilhus NE. Early child development and exposure to antiepileptic drugs prenatally and through breastfeeding: a prospective cohort study on children of women with epilepsy. JAMA Neurol, 2013, 70(11): 1367-1374.
28. 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(2): 396-404.
29. McVearry KM, Gaillard WD, VanMeter J, et al. A prospective study of cognitive fluency and originality in children exposed in utero to carbamazepine, lamotrigine, or valproate monotherapy. Epilepsy Behav, 2009, 16(4): 609-616.
30. Meador K, Baker G, Browning N, et al. Effects of fetal antiepileptic drug exposure: outcomes at age 4. 5 years. Neurology, 2012, 78(16): 1207-1214.
31. Veiby G, Daltveit AK, Schjolberg S, et al. Exposure to antiepileptic drugs in utero and child development: a prospective population-based study. Epilepsia, 2013, 54(8): 1462-1472.
32. Cohen MJ, Meador KJ, Browning N, et al. Fetal antiepileptic drug exposure: motor, adaptive, and emotional/behavioral functioning at age 3 years. Epilepsy Behav, 2011, 22(2): 240-246.
33. Cohen MJ, Meador KJ, Browning N, et al. Fetal antiepileptic drug exposure: adaptive and emotional/behavioral functioning at age 6 years. Epilepsy Behav, 2013, 29(2): 308-315.
34. Bromley RL, Mawer GE, Briggs M, et al. The prevalence of neurodevelopmental disorders in children prenatally exposed to antiepileptic drugs. J Neurol Neurosurg Psychiatry, 2013, 84(6): 637-643.
35. Christensen J, Pedersen L, Sun YL, et al. Association of prenatal exposure to valproate and other antiepileptic drugs with risk for attention-deficit/hyperactivity disorder in offspring. JAMA Netw Open, 2019, 2(1): e186606.
36. Christensen J, Grønborg TK, Sørensen MJ, et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA, 2013, 309(16): 1696-1703.
37. Richards N, Reith D, Stitely M, et al. Developmental outcomes at age four following maternal antiepileptic drug use. Epilepsy Behav, 2019, 93: 73-79.
38. Huber-Mollema Y, Oort FJ, Lindhout D, et al. Behavioral problems in children of mothers with epilepsy prenatally exposed to valproate, carbamazepine, lamotrigine, or levetiracetam monotherapy. Epilepsia, 2019, 60(6): 1069-1082.
39. Lacey AS, Pickrell WO, Thomas RH, et al. Educational attainment of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry, 2018, 89(7): 736-740.
40. Elkjær LS, Bech BH, Sun Y, et al. Association between prenatal valproate exposure and performance on standardized language and mathematics tests in school-aged children. JAMA Neurol, 2018, 75(6): 663-671.
41. Deshmukh U, Adams J, Macklin EA, et al. Behavioral outcomes in children exposed prenatally to lamotrigine, valproate, or carbamazepine. Neurotoxicol Teratol, 2016, 54: 5-14.
42. Shallcross R, Bromley RL, Irwin B, et al. Child development following in utero exposure: levetiracetam vs sodium valproate. Neurology, 2011, 76(4): 383-389.
43. Shallcross R, Bromley RL, Cheyne CP, et al. In utero exposure to levetiracetam vs valproate: development and language at 3 years of age. Neurology, 2014, 82(3): 213-221.
44. Guveli BT, Gurses C, Atakli D, et al. Behavioral characteristics and cognitive development among school age children born to women with epilepsy. Neurol Res, 2015, 37(4): 295-300.
45. Rihtman T, Parush S, Ornoy A. Preliminary findings of the developmental effects of in utero exposure to topiramate. Reprod Toxicol, 2012, 34(3): 308-311.
46. Adam MP, Polifka JE, Friedman JM. Evolving knowledge of the teratogenicity of medications in human pregnancy. Am J Med Genet C Semin Med Genet, 2011, 157C(3): 175-182.
47. Friedman JM. ABCDXXX: The obscenity of postmarketing surveillance for teratogenic effects. Birth Defects Res A Clin Mol Teratol, 2012, 94(8): 670-676.
48. Hernández-Díaz S, McElrath TF, Pennell PB, et al. Fetal growth and premature delivery in pregnant women on antiepileptic drugs. Ann Neurol, 2017, 82(3): 457-465.
49. Margulis AV, Mitchell AA, Gilboa SM, et al. Use of topiramate in pregnancy and risk of oral clefts. Am J Obstet Gynecol, 2012, 207(5): 405.e1-7.
50. Hernández-Díaz S, Smith CR, Shen A, et al. Comparative safety of antiepileptic drugs during pregnancy. Neurology, 2012, 78(21): 1692-1699.
51. Adab N, Vinten J, Kini U. Longer term outcome in children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry, 2003, 74(3): 400-401.
52. Medications and Healthcare products Regulatory Agency. Antiepileptic drugs: review of safety of use during pregnancy [R/OL]. [2021-02-01]. https://www.gov.uk/government/publications/public-assesment-report-of-antiepileptic-drugs-review-of-safety-of-use-during-pregnancy/antiepileptic-drugs-review-of-safety-of-use-during pregnancy.
53. Veroniki AA, Rios P, Cogo E, et al. Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis. BMJ Open, 2017, 7(7): e017248.
54. Bath KG, Scharfman HE. Impact of early life exposure to antiepileptic drugs on neurobehavioral outcomes based on laboratory animal and clinical research. Epilepsy Behav, 2013, 26(3): 427-439.
55. Bromley RL, Baker GA, Clayton-Smith J, et al. Intellectual functioning in clinically confirmed fetal valproate syndrome. Neurotoxicol Teratol, 2019, 71: 16-21.
56. Coste J, Blotière P-O, Miranda S, et al. Risk of early neurodevelopmental disorders associated with in utero exposure to valproate and other antiepileptic drugs: a nationwide cohort study in France. Nature, 2020, 10: 17362.
57. Vorhees CV. Behavioral teratology of anticonvulsant and antianxiety medications//Handbook of behavioral teratology. Springer, Boston, MA, 1986: 211-241.
58. Tong S, Baghurst P, Vimpani G, et al. Socioeconomic position, maternal iq, home environment, and cognitive development. J Pediatr, 2007, 151(3): 284-288.e1.
59. McGrath A, Sharpe L, Lah S, et al. Pregnancy-related knowledge and information needs of women with epilepsy: a systematic review. Epilepsy Behav, 2014, 31: 246-255.
60. Gerard EE. Preconception counseling for women with epilepsy//Women with epilepsy: a practical management handbook. Cambridge University Press, 2014: 141-156.
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