dostęp płatny
Leki przeciwpadaczkowe i bezpieczeństwo ich stosowania w okresie ciąży i karmienia piersią — przegląd aktualnych danych


- Zakład farmakologii, Wydział Nauk Medycznych w Katowicach, Śląski Uniwersytet Medyczny, ul. Medyków 18, 40-752 Katowice, Polska
- Student Wydziału Nauk o Zdrowiu w Katowicach, Śląskiego Uniwersytetu Medycznego, ul. Medyków 12, 40-752 Katowice, Polska
dostęp płatny
Streszczenie
Leczenie padaczki (epilepsji) u kobiety w ciąży to zadanie dla neurologa oraz ginekologa-położnika. Stosowanie leków przeciwpadaczkowych jest konieczne, mimo że może prowadzić do aberracji w przebiegu ciąży, ponieważ nieleczona padaczka stanowi zagrożenie dla matki i rozwijającego się płodu. FDA (Food and Drug Administration) oraz ADEC (Australian Drug Evaluation Comittee) wprowadziły klasyfikacje mające na celu określenie ryzyka uszkodzenia zarodka/płodu w wyniku stosowania leków. Najstarsze leki przeciwpadaczkowe (leki I-generacji) są bardzo skuteczne, jednakże wiadomo, ze ich stosowanie niesie ze sobą największe ryzyko indukcji anomalii u płodu. Dodatkowo, podobnie jak w przypadku stosowania benzodiazepin, istnieje ryzyko rozwoju u noworodków syndromu odstawienia. Leki II-generacji nie zostały dotychczas dokładnie przebadane pod kątem działania embriotoksycznego i teratogennego. Jednakże dostępne dane sugerują, że są to leki bezpieczniejsze. Benzodiazepiny stanowią odrębną grupę leków o potencjale przeciwdrgawkowym. Podawanie tych leków w okresie ciąży musi być wysoce uzasadnione, biorąc pod uwagę bilans korzyści i istotnych zagrożeń wynikających z ich stosowania.
Streszczenie
Leczenie padaczki (epilepsji) u kobiety w ciąży to zadanie dla neurologa oraz ginekologa-położnika. Stosowanie leków przeciwpadaczkowych jest konieczne, mimo że może prowadzić do aberracji w przebiegu ciąży, ponieważ nieleczona padaczka stanowi zagrożenie dla matki i rozwijającego się płodu. FDA (Food and Drug Administration) oraz ADEC (Australian Drug Evaluation Comittee) wprowadziły klasyfikacje mające na celu określenie ryzyka uszkodzenia zarodka/płodu w wyniku stosowania leków. Najstarsze leki przeciwpadaczkowe (leki I-generacji) są bardzo skuteczne, jednakże wiadomo, ze ich stosowanie niesie ze sobą największe ryzyko indukcji anomalii u płodu. Dodatkowo, podobnie jak w przypadku stosowania benzodiazepin, istnieje ryzyko rozwoju u noworodków syndromu odstawienia. Leki II-generacji nie zostały dotychczas dokładnie przebadane pod kątem działania embriotoksycznego i teratogennego. Jednakże dostępne dane sugerują, że są to leki bezpieczniejsze. Benzodiazepiny stanowią odrębną grupę leków o potencjale przeciwdrgawkowym. Podawanie tych leków w okresie ciąży musi być wysoce uzasadnione, biorąc pod uwagę bilans korzyści i istotnych zagrożeń wynikających z ich stosowania.
Pełny tekst:
Dodaj do koszyka: 15,00 PLN
Słowa kluczowe
leki przeciwpadaczkowe, ciąża, okres laktacji


Tytuł
Leki przeciwpadaczkowe i bezpieczeństwo ich stosowania w okresie ciąży i karmienia piersią — przegląd aktualnych danych
Czasopismo
Numer
Typ artykułu
Artykuł przeglądowy
Strony
88-104
Opublikowany online
2020-06-30
Wyświetlenia strony
1213
Wyświetlenia/pobrania artykułu
357
DOI
10.5603/PPN.2020.0015
Rekord bibliograficzny
Pol. Przegl. Neurol 2020;16(2):88-104.
Słowa kluczowe
leki przeciwpadaczkowe
ciąża
okres laktacji
Autorzy
Miłosz Jan Gołyszny
Oliwia Korzonek
Magdalena Durańska


- Walker SP, Permezel M, Berkovic SF. The management of epilepsy in pregnancy. BJOG. 2009; 116(6): 758–767.
- Alsmadi MM, Idkaidek N. Optimization of drugs pharmacotherapy during pregnancy using physiologically based pharmacokinetic models — an update. Curr Drug Metab. 2018; 19(12): 972–978.
- Battino D, Tomson T. Management of epilepsy during pregnancy. Drugs. 2007; 67(18): 2727–2746.
- Tomson T, Battino D, Bromley R, et al. Management of epilepsy in pregnancy: a report from the International League Against Epilepsy Task Force on Women and Pregnancy. Epileptic Disord. 2019; 21(6): 497–517.
- Trinka E, Cock H, Hesdorffer D, et al. A definition and classification of status epilepticus. Report of the ILAE Task Force on classification of status epilepticus. Epilepsia. 2015; 56(10): 1515–1523.
- EURAP Study Group. Seizure control and treatment in pregnancy: observations from the EURAP Epilepsy Pregnancy Registry. Neurology. 2005; 66(3): 354–360.
- Shorvon S, Tomson T. Sudden unexpected death in epilepsy. Lancet. 2011; 378(9808): 2028–2038.
- Edey S, Moran N, Nashef L. SUDEP and epilepsy-related mortality in pregnancy. Epilepsia. 2014; 55(7): e72–e74.
- Bargieł A, Bokiniec R, Kornacka MK. Risk factors for preterm encephalopathy. Ginekol Pol. 2009; 80(8): 620–623.
- Wijdicks EFM. Determining brain death in adults. Neurology. 1995; 45(5): 1003–1011.
- Tomson T, Battino D. Teratogenic effects of antiepileptic drugs. Lancet Neurol. 2012; 11(9): 803–813.
- Meador K, Reynolds M, Crean S, et al. Pregnancy outcomes in women with epilepsy: a systematic review and meta-analysis of published pregnancy registries and cohorts. Epilepsy Res. 2008; 81(1): 1–13.
- 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(7): 609–617.
- Pandey MK, Mittra P, Maheshwari P. Oxidative stress in epilepsy with comorbid psychiatric illness. Natl J Physiol Pharm Pharmacol. 2013; 3(1): 92.
- Holmes GL, Ben-Ari Y. The neurobiology and consequences of epilepsy in the developing brain. Pediatr Res. 2001; 49(3): 320–325.
- Werler MM, Ahrens KA, Bosco JLF, et al. Use of antiepileptic medications in pregnancy in relation to risks of birth defects. Ann Epidemiol. 2011; 21(11): 842–850.
- Tomson T, Battino D, Bonizzoni E, et al. EURAP: an International Registry of Antiepileptic Drugs and Pregnancy. Epilepsia. 2004; 45(11): 1463–1464.
- Bromley RL, Baker GA. Fetal antiepileptic drug exposure and cognitive outcomes. Seizure. 2017; 44: 225–231.
- Shorvon SD. The first 100 years of the ILAE (1909–2009): its landmarks, achievements, and challenges. Epilepsia Open. 2019; 4(2): 237–246.
- Brodie MJ, Kwan P. Current position of phenobarbital in epilepsy and its future. Epilepsia. 2012; 53: 40–46.
- Yasiry Z, Shorvon S. How phenobarbital revolutionized epilepsy therapy: the story of phenobarbital therapy in epilepsy in the last 100 years. Epilepsia. 2012; 53: 26–39.
- 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(6): 530–538.
- Zhang LL, Zeng LN, Li YP. Side effects of phenobarbital in epilepsy: a systematic review. Epileptic Disord. 2011; 13(4): 349–365.
- Arpino C, Brescianini S, Robert E, et al. Teratogenic effects of antiepileptic drugs: use of an International Database on Malformations and Drug Exposure (MADRE). Epilepsia. 2000; 41(11): 1436–1443.
- Adams J, Holmes LB, Janulewicz P. The adverse effect profile of neurobehavioral teratogens: phenobarbital. Neurotoxicol Teratol. 2004; 26(3): 507.
- El-Dib M, Soul J. The use of phenobarbital and other anti-seizure drugs in newborns. Semin Fetal Neonatal Med. 2017; 22(5): 321–327.
- Pizzo F, Dilaghi A, Romoli A, et al. Pregnancy in epileptic patients: comparison between well-established therapeutic strategies and opportunities coming from new drugs. Clinical Management Issues. 2013; 7(3): 91–98.
- Kazmin A, Wong RC, Sermer M, et al. Antiepileptic drugs in pregnancy and hemorrhagic disease of the newborn: an update. Can Fam Physician. 2010; 56(12): 1291–1292.
- Sarmento A, Soares P. Convulsões neonatais-qual a etiologia? Nascer e Crescer. 2004; 13(2): 106–112.
- Lander CM. Antiepileptic drugs in pregnancy and lactation. Aust Prescriber. 2008; 31(3): 70–72.
- Davanzo R, Bo SD, Bua J, et al. Antiepileptic drugs and breastfeeding. Ital J Pediatr. 2013; 39(1): 50.
- Veiby G, Bjørk M, Engelsen B, et al. Epilepsy and recommendations for breastfeeding. Seizure. 2015; 28: 57–65.
- Jackson L. A randomised controlled trial of morphine versus phenobarbitone for neonatal abstinence syndrome. Arch Dis Child Fetal Neonatal Ed. 2004; 89(4): F300–F304.
- Mutschler E. Dynamics of pharmacology and toxicology drugs. ITB, Bandung 1999: 56–62.
- Loughnan PM, Vance JC, Gold H. Phenytoin teratogenicity in man. Lancet. 1973; 301(7794): 70–72.
- Hanson JW, Smith DW. The fetal hydantoin syndrome. J Pediatr. 1975; 87(2): 285–290.
- Hanson JW, Smith DW. Fetal hydantoin syndrome. Lancet. 1976; 1(7961): 692.
- Hanson JW. Fetal hydantoin effects. Teratology. 1986; 33(3): 349–353.
- Hegde A, Kaur A, Sood A, et al. Fetal hydantoin syndrome. J Pediatr. 2017; 188: 304.
- Czeizel AE, Bod M, Halász P. Evaluation of anticonvulsant drugs during pregnancy in a population-based Hungarian study. Eur J Epidemiol. 1992; 8(1): 122–127.
- Oguni M, Dansky L, Andermann E, et al. Improved pregnancy outcome in epileptic women in the last decade: Relationship to maternal anticonvulsant therapy. Brain Dev. 1992; 14(6): 371–380.
- Borgelt L, Hart F, Bainbridge J. Epilepsy during pregnancy: focus on management strategies. Int J Womens Health. 2016; 8: 505–517.
- Allen RW. Fetal hydantoin syndrome, neuroblastoma, and hemorrhagic disease in a neonate. JAMA. 1980; 244(13): 1464–1465.
- Eadie MJ, Vajda F. (eds.). Antiepileptic drugs. Pharmacology and therapeutics. Springer Science & Business Media, Basel 2012.
- Harden CL, Meador KJ, Pennell PB, et al. Practice parameter update: management issues for women with epilepsy — focus on pregnancy (an evidence-based review): Teratogenesis and perinatal outcomes: 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(2): 133–141.
- 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(2): 142–149.
- Hernández-Díaz S, Werler MM, Walker AM, et al. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med. 2000; 343(22): 1608–1614.
- Bell RD, Pak CYC, Zerwekh J, et al. Effect of phenytoin on bone and vitamin D metabolism. Ann Neurol. 1979; 5(4): 374–378.
- Espinosa PS, Perez DL, Abner E, et al. Association of antiepileptic drugs, vitamin D, and calcium supplementation with bone fracture occurrence in epilepsy patients. Clin Neurol Neurosurg. 2011; 113(7): 548–551.
- 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(7): 609–617.
- Jentink J, Loane M, Dolk H, et al. Valproic acid monotherapy in pregnancy and major congenital malformations. N Engld J Med. 2010; 362(23): 2185–2193.
- Morrow J. Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register. J Neurol Neurosurg Psychiatry. 2006; 77(2): 193–198.
- Meador KJ, Baker GA, Finnell RH, et al. In utero antiepileptic drug exposure: fetal death and malformations. Neurology. 2006; 67(3): 407–412.
- Özkan H, Çetinkaya M, Köksal N, et al. Severe fetal valproate syndrome: combination of complex cardiac defect, multicystic dysplastic kidney, and trigonocephaly. J Matern Fetal Neonatal Med. 2011; 24(3): 521–524.
- Pennell PB, Klein AM, Browning N, et al. Differential effects of antiepileptic drugs on neonatal outcomes. Epilepsy Behav. 2012; 24(4): 449–456.
- Almgren M, Källén B, Lavebratt C. Population-based study of antiepileptic drug exposure in utero — influence on head circumference in newborns. Seizure. 2009; 18(10): 672–675.
- Shallcross R, Bromley RL, Irwin B, et al. Child development following in utero exposure: levetiracetam vs sodium valproate. Neurology. 2011; 76(4): 383–389.
- Christensen J, Grønborg T, Sørensen M, et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA. 2013; 309(16): 1696.
- Uguz F, Sharma V. Mood stabilizers during breastfeeding: a systematic review of the recent literature. Bipolar Disord. 2016; 18(4): 325–333.
- Vajda FJE, Graham J, Roten A, et al. Teratogenicity of the newer antiepileptic drugs — the Australian experience. J Clin Neurosci. 2012; 19(1): 57–59.
- Vajda FJE, O’Brien TJ, Graham J, et al. Is carbamazepine a human teratogen? J Clin Neurosci. 2016; 23: 34–37.
- Akar M, Dilli D, Yilmaz Y. A case of fetal carbamazepine syndrome with right hemihypoplasia of the entire body. Genetic Couns. 2012; 23(1): 19.
- Cummings C, Stewart M, Stevenson M, et al. Neurodevelopment of children exposed in utero to lamotrigine, sodium valproate and carbamazepine. Archiv Dis Child. 2011; 96(7): 643–647.
- Nadebaum C, Anderson VA, Vajda F, et al. Language skills of school-aged children prenatally exposed to antiepileptic drugs. Neurology. 2011; 76(8): 719–726.
- Pennell PB. Use of antiepileptic drugs during pregnancy: evolving concepts. Neurotherapeutics. 2016; 13(4): 811–820.
- Sabers A, Tomson T. Managing antiepileptic drugs during pregnancy and lactation. Curr Opin Neurol. 2009; 22(2): 157–161.
- Dodd S, Berk M. The safety of medications for the treatment of bipolar disorder during pregnancy and the puerperium. Curr Drug Saf. 2006; 1(1): 25–33.
- Holmes LB. Fetal effects of anticonvulsant polytherapies. Archiv Neurol. 2011; 68(10): 1275.
- Hernandez-Diaz S, Smith CR, Shen A, et al. Comparative safety of antiepileptic drugs during pregnancy. Neurology. 2012; 78(21): 1692–1699.
- Cunnington M, Tennis P. Lamotrigine and the risk of malformations in pregnancy. Neurology. 2005; 64(6): 955–960.
- Vajda FJE, Graham JE, Hitchcock AA, et al. Is lamotrigine a significant human teratogen? Observations from the Australian Pregnancy Register. Seizure. 2010; 19(9): 558–561.
- Campbell E, Kennedy F, Irwin B, et al. Malformation risks of antiepileptic drug monotherapies in pregnancy. J Neurol Neurosurg Psychiatry. 2013; 84(11): e2.148–e2.
- Dolk H, Wang H, Loane M, et al. Lamotrigine use in pregnancy and risk of orofacial cleft and other congenital anomalies. Neurology. 2016; 86(18): 1716–1725.
- Wlodarczyk BJ, Palacios AM, George TM, et al. Antiepileptic drugs and pregnancy outcomes. Am J Med Genet A. 2012; 158A(8): 2071–2090.
- Hunt SJ, Craig JJ, Morrow JI, et al. Increased frequency of isolated cleft palate in infants exposed to lamotrigine during pregnancy. Neurology. 2009; 72(12): 1108–1109.
- Newport DJ, Pennell PB, Calamaras MR, et al. Lamotrigine in breast milk and nursing infants: determination of exposure. Pediatrics. 2008; 122(1): e223–e231.
- Meischenguiser R, D'Giano C, Ferraro S. Oxcarbazepine in pregnancy: clinical experience in Argentina. Epilepsy Behav. 2004; 5(2): 163–167.
- Artama M, Auvinen A, Raudaskoski T, et al. Antiepileptic drug use of women with epilepsy and congenital malformations in offspring. Neurology. 2005; 64(11): 1874–1878.
- Mølgaard-Nielsen D, Hviid A. Newer-generation entiepileptic drugs and the risk of major birth defects. JAMA. 2011; 305(19).
- Reimers A, Brodtkorb E. Second-generation antiepileptic drugs and pregnancy: a guide for clinicians. Expert Rev Neurother. 2014; 12(6): 707–717.
- Montouris G. Safety of the newer antiepileptic drug oxcarbazepine during pregnancy. Curr Med Res Opin. 2005; 21(5): 693–701.
- Uludag S. Oxcarbazepine/topiramate multiple fetal anomalies following in utero. Reactions. 2012; 1407: 23.
- 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.
- Kaaja E, Kaaja R, Hiilesmaa V. Major malformations in offspring of women with epilepsy. Neurology. 2003; 60(4): 575–579.
- Hvas CL, Henriksen T, ostergaard J, et al. Epilepsy and pregnancy: effect of antiepileptic drugs and lifestyle on birthweight. BJOG. 2000; 107(7): 896–902.
- Oyebode F, Rastogi A, Berrisford G, et al. Psychotropics in pregnancy: safety and other considerations. Pharmacol Ther. 2012; 135(1): 71–77.
- Hunt S, Russell A, Smithson WH, et al. Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology. 2008; 71(4): 272–276.
- 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.
- Koo J, Zavras A. Antiepileptic drugs (AEDs) during pregnancy and risk of congenital jaw and oral malformation. Oral Dis. 2013; 19(7): 712–720.
- Bromley RL, Weston J, Marson AG. Maternal use of antiepileptic agents during pregnancy and major congenital malformations in children. JAMA. 2017; 318(17): 1700.
- Green MW, Seeger J, Peterson C, et al. Utilization of topiramate during pregnancy and risk of birth defects. Headache. 2012; 52(7): 1070–1084.
- 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.
- López-Fraile IP, Cid A, Juste A, et al. Levetiracetam plasma level monitoring during pregnancy, delivery, and postpartum: Clinical and outcome implications. Epilepsy Behav. 2009; 15(3): 372–375.
- Scheuerle AE, Holmes L, Albano J, et al. Levetiracetam Pregnancy Registry: final results and a review of the impact of registry methodology and definitions on the prevalence of major congenital malformations. Birth Defects Res. 2019; 111(13): 872–887.
- Montouris G, Harden, C, Alekar S, et al. UCB Antiepileptic Drug Pregnancy Registry-Keppra® data. American Epilepsy Society. 2010; abstracts: 1–257.
- Longo B, Forinash A, Murphy J. Drug information rounds levetiracetam use in pregnancy. Ann Pharmacother. 2009; 43(10): 1692–1695.
- Long L. Levetiracetam monotherapy during pregnancy: a case series. Epilepsy Behav. 2003; 4(4): 447–448.
- Bromley RL, Calderbank R, Cheyne C, et al. Cognition in school-age children exposed to levetiracetam, topiramate, or sodium valproate. Neurology. 2016; 87(18): 1943–1953.
- Chaudhry SA, Jong G, Koren G. The fetal safety of levetiracetam: a systematic review. Reprod Toxicol. 2014; 46: 40–45.
- Holmes LB, Hernandez-Diaz S. Newer anticonvulsants: lamotrigine, topiramate and gabapentin. Birth Defects Res A Clin Mol Teratol. 2012; 94(8): 599–606.
- Guttuso T, Shaman M, Thornburg. LL. Potential maternal symptomatic benefit of gabapentin and review of its safety in pregnancy. Eur J Obstet Gynecol Reprod Biol. 2014; 181: 280–283.
- Montouris G. Gabapentin exposure in human pregnancy: results from the Gabapentin Pregnancy Registry. Epilepsy Behav. 2003; 4(3): 310–317.
- Fujii H, Goel A, Bernard N, et al. Pregnancy outcomes following gabapentin use: results of a prospective comparative cohort study. Neurology. 2013; 80(17): 1565–1570.
- Rolnitsky A, Merlob P, Klinger G. In utero oxcarbazepine and a withdrawal syndrome, anomalies, and hyponatremia. Pediatr Neurol. 2013; 48(6): 466–468.
- Rejdak R, Rola R, Mazurkiewicz-Bełdzińska M. Diagnosis and treatment of epilepsy in adults — recommendations of the Polish Neurological Society. Pol Przegl Neurol. 2016; 12(1): 15–27.
- Trinka E, Shorvon S. A decade of progress in status epilepticus 2007–2017: proceedings of the 6th London–Innsbruck Colloquium on Status Epilepticus and Acute Seizures. Epilepsia. 2018; 59: 67–69.
- Bresnahan R, Martin-McGill K, Williamson J, et al. Clobazam add-on therapy for drug-resistant epilepsy. Cochrane Database Syst Rev. 2019(10): CD004154.
- Perault MC, Favrelière S, Minet P, et al. [Benzodiazepines and pregnancy] [Article in French]. Therapie. 2000; 55(5): 587–595.
- Dolovich LR. Teratogenicity of benzodiazepines assessed. Reactions. 1998; 721: 3.
- Iqbal MM, Sobhan T, Aftab SR, et al. Diazepam use during pregnancy: a review of the literature. Del Med J. 2002; 74(3): 127–135.
- Enato E, Moretti M, Koren G. Motherisk rounds: the fetal safety of benzodiazepines: an updated meta-analysis. J Obstet Gynaecol Can. 2011; 33(1): 46–48.
- Lin AE, Peller AJ, Westgate MN, et al. Clonazepam use in pregnancy and the risk of malformations. Birth Defects Res A Clin Mol Teratol. 2004; 70(8): 534–536.
- Azparren A, Garcia I. Strategies for discontinuing benzodiazepines. Drug Ther Bull Navarre. 2014; 22: 1–12.
- Kelly LE, Poon S, Madadi P, et al. Neonatal benzodiazepines exposure during breastfeeding. J Pediatr. 2012; 161(3): 448–451.
- Soussan C, Gouraud A, Portolan G, et al. Drug-induced adverse reactions via breastfeeding: a descriptive study in the French Pharmacovigilance Database. Eur J Clin Pharmacol. 2014; 70(11): 1361–1366.
- https://www medicines org uk/emc/product/4524/smpc (April 17, 2020).
- Czeizel AE, Erös E, Rockenbauer M, et al. Short-term oral diazepam treatment during pregnancy. Clin Drug Invest. 2003; 23(7): 451–462.
- Kjær D, Horvath-Puhó E, Christensen J, et al. Use of phenytoin, phenobarbital, or diazepam during pregnancy and risk of congenital abnormalities: a case-time-control study. Pharmacoepidemiol Drug Saf. 2007; 16(2): 181–188.
- Gidai J, Ács N, Bánhidy F, et al. No association found between use of very large doses of diazepam by 112 pregnant women for a suicide attempt and congenital abnormalities in their offspring. Toxicol Ind Health. 2008; 24(1-2): 29–39.
- https://www medicines org uk/emc/product/6022/smpc (April 17, 2020).
- Jarita D, Errol F, Thomas M, et al. Risk of malformation with combination of lamotrigine and low dose clonazepam for juvenile myoclonic epilepsy in pregnancy: a case report. Neurology Asia. 2010; 15(1): 79–81.
- Bansal R, Suri V, Chopra S, et al. Change in antiepileptic drug prescription patterns for pregnant women with epilepsy over the years: Impact on pregnancy and fetal outcomes. Ind J Pharmacol. 2019; 51(2): 93.
- Andrade C. Gestational exposure to benzodiazepines, 3: clobazam and major congenital malformations. J Clin Psychiatry. 2019; 80(6): 19f13151.
- Iqbal M, Sobhan T, Ryals T. Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant. Psychiatric Serv. 2002; 53(1): 39–49.
- Bais B, Molenaar NM, Bijma HH, et al. Prevalence of benzodiazepines and benzodiazepine-related drugs exposure before, during and after pregnancy: A systematic review and meta-analysis. J Affect Disord. 2020; 269: 18–27.
- Wikner BN, Stiller CO, Bergman U, et al. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: neonatal outcome and congenital malformations. Pharmacoepidemiol Drug Saf. 2007; 16(11): 1203–1210.