drjanak
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Teratogenecity of anticonvulsants
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07.14.08 (2 months ago)
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Williams Obstetrics 22nd edition Section VIII. Medical and Surgical Complications > Chapter 55. Neurological and Psychiatric Disorders > Epilepsy During Pregnancy>Management>Preconceptional Counseling
Although some clinicians recommend that medications be limited if possible to the older, more traditional anticonvulsants, namely, phenytoin, carbamazepine, and phenobarbital, some newer drugs may actually have less teratogenic potential……. Folic acid supplementation should also be given
Williams Obstetrics 22nd Section III. Antepartum > Chapter 14. Teratology, Drugs, and Other Medications
Disruption of Folic Acid Metabolism
Several congenital anomalies, including neural-tube defects, cardiac defects, cleft lip and palate, and even Down syndrome, are thought to arise, at least in part, from disturbance of folic acid metabolic pathways. Folic acid is essential for the production of methionine, which is required for methylation reactions and thus production of proteins, lipids, and myelin (Scott and associates, 1994). It is essential for normal meiosis and mitosis. Hydantoin, carbamazepine, valproic acid, and phenobarbital all impair folate absorption or act as antagonists. They can lead to decreased periconceptional folate levels in women with epilepsy and to fetal malformations (Dansky and colleagues, 1987; Hiilesmaa and co-workers, 1983). A recent study by Hernandez-Diaz and colleagues (2000), including 5832 infants with birth defects and 8387 control infants, showed that fetuses who were exposed during embryogenesis to antiseizure medications known to act as folic acid antagonists had a two- to threefold increased risk for oral clefts, cardiac defects, and urinary tract defects. Although periconceptional folate supplementation lowers the malformation rate, women with epilepsy should be given the fewest number of drugs possible during pregnancy as well as folic acid supplementation (Lewis and co-workers, 1998; Zhu and Zhou, 1989)
Antiepileptic Drugs
Many commonly used anticonvulsants are teratogenic, as discussed in Anticonvulsant Medications. Ethosuxamide and methsuximide are succinimide derivatives used for petit mal seizures. There are no human reproductive studies available and there are no case reports of malformations attributed solely to either of these agents. Information about the safety of newer anticonvulsants, including felbamate, gabapentin, oxcarbazepine, tiagabin, and vigabatrin, is limited (Briggs and associates, 2002). Based on what is known about the likely mechanisms of teratogenesis of traditional anticonvulsants, some of these newer drugs may prove to be safer for the fetus. For example, none of these new agents has antifolate effects, nor do they result in arene oxide metabolites, and most have minimal or no effect on the cytochrome P450 system (Morrell, 1996).
The answer seems to be Gabapentin though I personally think it would be a brave obstetrician who did not prescribe folic acid supplements with any of the anticonvulsants during pregnancy.
The text books do not clearly mention that “do not give folic acid with any of the anticonvulsants” – in fact quite to the contrary. Hence though I would mark the answer as Gabapentin, I not happy about it.
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drjanak
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Teratogenicityof anticonvulsants
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07.14.08 (2 months ago)
#3
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A few more references:
Danforth's Obstetrics and Gynecology
, 10th Edition 17 - Medical and Surgical Complications of PregnancyEpilepsy
Most epileptic women require seizure medication to remain seizurefree. For many anticonvulsant drugs, the benefit of preventing seizures outweighs any potential risks to the fetus. Some medications are clearly teratogenic and should be avoided, if possible; these include valproic acid before 8 weeks gestation. However, women with epilepsy are at increased risk for fetal malformations, whether or not they ingest anticonvulsant medication. Although women taking multiple medications are at highest risk, it is not clear whether the increased risk is due to fetal drug exposure or whether it correlates with severity of maternal disease.
The lowest medication dosage associated with seizure prevention should be prescribed. Stressors should be minimized, and the patient should ingest a multivitamin with folate.
GOODMAN & GILMAN'S THE PHARMACOLOGICAL BASIS OF THERAPEUTICS - 11th Ed. (2006)
CHAPTER 19. PHARMACOTHERAPY OF THE EPILEPSIES
Antiseizure Therapy and Pregnancy
Folate supplementation (0.4 mg/day) has been recommended by the U.S. Public Health Service for all women of childbearing age to reduce the likelihood of neural tube defects, and this is appropriate for epileptic women as well.
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