Fetal Effects of Anticonvulsant Polytherapies

Abstract

To determine the frequency of malformations among infants born to women who had taken lamotrigine or carbamazepine as part of polytherapy during the first trimester of pregnancy.

Antiepileptic drug polytherapy in pregnant women with epilepsy

“…The findings of the present study, like those of several reasonably recent investigations, 16,[24][25][26][27] do not support the earlier published belief that AED polytherapy in its own right increases the hazard of foetal malformation. The newer evidence has indicated that the heightened malformation risk with AED polytherapy depends on the presence of valproate in AED combinations, while the present data suggest that topiramate, in polytherapy, may have a similar effect.…”

“…The rationale underlying the anticipation of benefit from this approach depends on the initial AED used having been taken to its maximum tolerated effect before another drug is added, and the Register did not trace information back far enough to ensure that this requirement had been met.The findings of the present study, like those of several reasonably recent investigations,16,[24][25][26][27] do not support the earlier published belief that AED polytherapy in its own right increases the hazard of foetal malformation. The explicit reason for employing polytherapy was not recorded in the Register, but the fact that the polytherapy population had a longer mean duration of seizure disorder than the monotherapy population, despite similar mean ages at onset of pregnancy, had a shorter mean duration of seizure freedom prior to pregnancy and had a lower rate of freedom from seizures during pregnancy, are consistent with this interpretation.The study provided no evidence that pharmacologically rational antiepileptic drug combinations involving agents with different molecular mechanisms of action yielded a better chance of seizure freedom during pregnancy than combinations of drugs with similar molecular mechanisms of action.…”

Antiepileptic drug polytherapy in pregnant women with epilepsy

“…The findings of the present study, like those of several reasonably recent investigations, 16,[24][25][26][27] do not support the earlier published belief that AED polytherapy in its own right increases the hazard of foetal malformation. The newer evidence has indicated that the heightened malformation risk with AED polytherapy depends on the presence of valproate in AED combinations, while the present data suggest that topiramate, in polytherapy, may have a similar effect.…”

“…The rationale underlying the anticipation of benefit from this approach depends on the initial AED used having been taken to its maximum tolerated effect before another drug is added, and the Register did not trace information back far enough to ensure that this requirement had been met.The findings of the present study, like those of several reasonably recent investigations,16,[24][25][26][27] do not support the earlier published belief that AED polytherapy in its own right increases the hazard of foetal malformation. The explicit reason for employing polytherapy was not recorded in the Register, but the fact that the polytherapy population had a longer mean duration of seizure disorder than the monotherapy population, despite similar mean ages at onset of pregnancy, had a shorter mean duration of seizure freedom prior to pregnancy and had a lower rate of freedom from seizures during pregnancy, are consistent with this interpretation.The study provided no evidence that pharmacologically rational antiepileptic drug combinations involving agents with different molecular mechanisms of action yielded a better chance of seizure freedom during pregnancy than combinations of drugs with similar molecular mechanisms of action.…”

Antiepileptic drug combinations not involving valproate and the risk of fetal malformations

“…The presence of either valproate or topiramate in an AED combination appears to suggest that use of AEDs in combination tends to be associated with a greater risk of teratogenicity than the overall use of AEDs in monotherapy. Consistent with the conclusions of recent reports, [6][7][8] it is not the combining of AEDs per se, but the properties of the specific drugs that are combined, that appears to determine the malformation risk. This study provides evidence that topiramate should join valproate as drugs associated with increased fetal malformation risk.…”

Antiepileptic drugs and foetal malformation: analysis of 20 years of data in a pregnancy register

“…The association found in the present analysis between previous pregnancies where there has been a foetal malformation and current malformation-carrying pregnancy, was noted earlier [23]. It raises the possibility that genetic factors may play a role of AED -related foetal malformation.…”

Antiepileptic drug polytherapy in pregnant women with epilepsy

“…The findings of the present study, like those of several reasonably recent investigations, 16,[24][25][26][27] do not support the earlier published belief that AED polytherapy in its own right increases the hazard of foetal malformation. The newer evidence has indicated that the heightened malformation risk with AED polytherapy depends on the presence of valproate in AED combinations, while the present data suggest that topiramate, in polytherapy, may have a similar effect.…”

“…The rationale underlying the anticipation of benefit from this approach depends on the initial AED used having been taken to its maximum tolerated effect before another drug is added, and the Register did not trace information back far enough to ensure that this requirement had been met.The findings of the present study, like those of several reasonably recent investigations,16,[24][25][26][27] do not support the earlier published belief that AED polytherapy in its own right increases the hazard of foetal malformation. The explicit reason for employing polytherapy was not recorded in the Register, but the fact that the polytherapy population had a longer mean duration of seizure disorder than the monotherapy population, despite similar mean ages at onset of pregnancy, had a shorter mean duration of seizure freedom prior to pregnancy and had a lower rate of freedom from seizures during pregnancy, are consistent with this interpretation.The study provided no evidence that pharmacologically rational antiepileptic drug combinations involving agents with different molecular mechanisms of action yielded a better chance of seizure freedom during pregnancy than combinations of drugs with similar molecular mechanisms of action.…”

Antiepileptic drug combinations not involving valproate and the risk of fetal malformations

“…The presence of either valproate or topiramate in an AED combination appears to suggest that use of AEDs in combination tends to be associated with a greater risk of teratogenicity than the overall use of AEDs in monotherapy. Consistent with the conclusions of recent reports, [6][7][8] it is not the combining of AEDs per se, but the properties of the specific drugs that are combined, that appears to determine the malformation risk. This study provides evidence that topiramate should join valproate as drugs associated with increased fetal malformation risk.…”

Antiepileptic drugs and foetal malformation: analysis of 20 years of data in a pregnancy register

“…The association found in the present analysis between previous pregnancies where there has been a foetal malformation and current malformation-carrying pregnancy, was noted earlier [23]. It raises the possibility that genetic factors may play a role of AED -related foetal malformation.…”

Antiepileptic drug polytherapy in pregnant women with epilepsy

“…The findings of the present study, like those of several reasonably recent investigations, 16,[24][25][26][27] do not support the earlier published belief that AED polytherapy in its own right increases the hazard of foetal malformation. The newer evidence has indicated that the heightened malformation risk with AED polytherapy depends on the presence of valproate in AED combinations, while the present data suggest that topiramate, in polytherapy, may have a similar effect.…”

“…The rationale underlying the anticipation of benefit from this approach depends on the initial AED used having been taken to its maximum tolerated effect before another drug is added, and the Register did not trace information back far enough to ensure that this requirement had been met.The findings of the present study, like those of several reasonably recent investigations,16,[24][25][26][27] do not support the earlier published belief that AED polytherapy in its own right increases the hazard of foetal malformation. The explicit reason for employing polytherapy was not recorded in the Register, but the fact that the polytherapy population had a longer mean duration of seizure disorder than the monotherapy population, despite similar mean ages at onset of pregnancy, had a shorter mean duration of seizure freedom prior to pregnancy and had a lower rate of freedom from seizures during pregnancy, are consistent with this interpretation.The study provided no evidence that pharmacologically rational antiepileptic drug combinations involving agents with different molecular mechanisms of action yielded a better chance of seizure freedom during pregnancy than combinations of drugs with similar molecular mechanisms of action.…”

Antiepileptic drug combinations not involving valproate and the risk of fetal malformations

“…The presence of either valproate or topiramate in an AED combination appears to suggest that use of AEDs in combination tends to be associated with a greater risk of teratogenicity than the overall use of AEDs in monotherapy. Consistent with the conclusions of recent reports, [6][7][8] it is not the combining of AEDs per se, but the properties of the specific drugs that are combined, that appears to determine the malformation risk. This study provides evidence that topiramate should join valproate as drugs associated with increased fetal malformation risk.…”

Antiepileptic drugs and foetal malformation: analysis of 20 years of data in a pregnancy register

“…The association found in the present analysis between previous pregnancies where there has been a foetal malformation and current malformation-carrying pregnancy, was noted earlier [23]. It raises the possibility that genetic factors may play a role of AED -related foetal malformation.…”