Treatment goals attempt to achieve seizure control with monotherapy and with medications considered less teratogenic (Aguglia, 2009; Tomson, 2009). As discussed in detail in Chapter 60 (p. 1159) and shown in Table 8-2, some one-drug regimens are more teratogenic than others. Valproic acid, in particular, is avoided if possible, as this medication has consistently been associated with a greater risk for major congenital malformations than other antiepileptic drugs Qentink, 2010; Vajda, 2015). Trimethadione is contraindicated (Aghajanian, 2015). he American Academy of Neurology recommends consideration of antiseizure medication discontinuation before pregnancy in suitable candidates Qeha, 2005). hese include women who satisy the following criteria: (1) have been seizure-free for 2 to 5 years, (2) display a single seizure type, (3) have a normal neurological examination and normal intelligence, and (4) showeelectroencephalogram results that have normalized with treatment.
Epileptic women should be advised to daily take a 4-mg folic acid supplement. Even so, it is not entirely clear that folate supplementation reduces the fetal malformation risk in pregnant women taking anticonvulsant therapy. In one case-control study, Kjer and associates (2008) reported that the congenital abnormality risk was reduced by maternal folate supplementation in fetuses exposed to carbamazepine, phenobarbitl, phenytoin, and primidone. Conversely, from the United Kingdom Epilepsy and
TABLE 8-2. First-Trimester .ntiepileptic Monotherapy and the Associated Major Malformation Risk
Unexposed controls (442) 1.1 Reference
Lamotrigine (1 562) 2.0 1.8 (0.7-4.6)
Carbamazepine (1 033) 3.0 2.7 (1 .0-7.0)
Phenytoin (4 16) 2.9 2.6 (0.9-7.4)
Levetiracetam (450) 2.4 2.2 (0.8-6.4)
Topiramate (359) 4.2 3.8 (1 .4-10.6)
Valproate (323) 9.3 9.0 (3.4-23.3)
Phenobarbital (1 99) 5.5 5.1 (1 .8-1 4.9) Oxcarbazepine (1 82) 2.2 2.0 (0.5-7.4)
Gabapentin (1 45) 0.6 (0.07-5.2)
Clonazepam (64) 3.1 2.8 (0.5-14.8) aRisk compared with that of the unexposed reference population of nonepileptic women.
n =number of exposed infants.
Data from Hernandez-Oraz 5, Smith CR, Shen A., et al: Comparative safety of antiepileptic drugs during pregnancy. Neurology 78:1692, 2012.
Pregnancy Register, Morrow and coworkers (2009) compared fetal outcomes of women who received preconceptional folic acid with those who did not receive it until later in pregnancy or not at all. In this study, a paradoxical increse in the number of major congenital malformations was observed in the group who received preconceptional folate. hese investigators concluded that folate metabolism may be only a part of the mechanism by which malformations are induced in women taking these medications.