|
Management issues for Women with Epilepsy (WWE) |
| Ovarian
hormone |
 | Estrogen: may lower seizure threshold,
decreases GABA. It has never been shown that estrogen-containing oral contraceptives worsen seizures. |
| Progesterone: may protect against seizure, increases GABA |
|
| Fertility
 | Fertility 2/3 of that expected in the general
population. |
| Lower marriage rate. |
| Perinatal and neonatal mortality
higher. |
| Women with temporal lobe epilepsy, with or without AED have
more menstrual dysfunction and reproductive endocrine disorders. |
|
|
| Contraception
| Probably no change on efficacy of
oral contraceptives
 | Felbatol, Gabapentin, Lamotrigine,
Valproate, Vigabatrin |
|
| Decrease efficacy of oral
contraceptives
| Barbiturates, Carbamazepine,
Phenytoin, Primidone, Primidone, Tiagabine, Topiramate |
|
|
| Induce hepatic cytochrome P450 system.
| Phenobarbital, Primidone, Phenytoin, Carbamazepine, and
Topiramate |
| Increase steroid hormone
binding globulins, decrease free hormone. |
|
| Valproic acid and Felbamate inhibit hepatic microsomal
enzyme system. |
| Gabapentin, Lamotrigine,
and Vigabatrin, appear to have no significant effect. |
|
| Pregnancy-related
management issues |
| Folic acid supplement in woman with
epilepsy |
| Low serum and erythrocyte folate levels have been
associated with spontaneous abortion and fetal malformations. |
| Phenytoin, Carbamazepine, and barbiturates, can impair
folate absorption. |
| Maternal Valproic acid and Carbamazepine use increase risk
of neural tube defects in infants at 1 to 2% and 0.5 to 1%, respectively. |
| Maternal folic acid supplement reduces the risk of neural
tube defects for infants in the general population. |
| CDC recommends 0.4 mg/day in all women of childbearing
age. |
| The Canadian College of Medical Geneticists recommends
folic acid up to 5 mg/day for women who had a child with a neural tube defect. |
|
| Obstetric outcomes in woman with
epilepsy |
| Increased risk for pregnancy complications. |
| Socioeconomic factors may play a significant role. |
| Obstetric complications reported to occur with increased
frequency: vaginal bleeding, hyperemesis gravidarum, ectopic pregnancy, spontaneous
abortion, premature labor and preterm delivery, forceps or vacuum assisted delivery,
cesarean section, stillbirth, and neonatal death. |
|
| Seizure
control during pregnancy |
| According to recent studies, approximately 20-33% of patients will have an increase in their seizures, 7-25% a decrease in seizures, and 50-83% will experience no significant change. |
| Effect of partial complex and absence seizures on fetus is
unknown. |
| Studies have shown that sleep-deprivation or noncompliance played a clear role in up to 70% of women with an increase in seizures during pregnancy. |
| Regular monitoring of AED levels during pregnancy is
recommended. |
| As pregnancy progresses
| Total AED level may decrease |
| Free AED may increase, especially the highly protein-bound Phenytoin and
Valproate. |
|
| The physiologic changes of pregnancy are reversed quickly
in postpartum: If AED dose was increased during pregnancy, toxic levels may develop
after delivery. |
|
| AED teratogenesis |
| No known teratogenicity |
Known to have teratogenicity |
| Felbatol, Gabapentin, Lamotrigine,
Tiagabine |
Barbiturates,
Carbamazepine,
Primidone, Phenytoin, Topiramate, Valproate |
|
| Major malformations (structural abnormalities that require
surgical intervention to prevent death or significant dysfunction)
| General population: 2 to 3% |
| WWE taking AEDs: 4 to 6%. |
|
| This increase in risk may be multifactorial, although all
AEDs commonly used are associated with the occurrence of birth defects. |
| Seizures during pregnancy are not linked to increased risk
for malformations. An exception is Lindhout et al.'s report of a 12.3% malformation
rate in WWE experiencing first trimester seizures compared with 4% in women without first
trimester seizures. |
| Case reports initially suggested drug-specific syndromes,
there is a great overlap in the described dysmorphisms. Specific syndromes are no longer
accepted, and the broader term, Fetal AED syndrome, is more
appropriate, maternal epilepsy and hereditary factors have a contributing role. |
| Recommend: counsel the WWE and her partner in terms of
minimizing risk birth defects.
| increased risk with multiple AEDs & high AED levels |
| contributions of heredity and seizure occurrence during
pregnancy |
|
|
| Major Malformations in
Infants of epileptic mothers compared to the General Population |
| |
General Population |
Infants of epileptic mothers |
| Congenital
heart |
0.5% |
1.5-2% |
| Cleft
lip/palate |
0.15% |
1.4% |
| Neural tube
defect |
0.1% |
1-2%
(VPA), 0.5-1% (CBZ) |
|
| Vitamin K to prevent Hemorrhagic disease
of the Newborn (HDN) |
| Vitamin K1 is given as 10 mg/day orally during the last month of pregnancy, followed by 1 mg IM/IV to the newborn |
| HDN typically occurs 2 to 7 days after birth, early (under
24 hours) and delayed (over 1 month) forms are described. |
| Exclusive breast-feeding, concurrent illness, and omission
of neonatal administration of vitamin K have been implicated in the delayed form. |
| The maternal use of hepatic-enzyme-inducing drugs,
including AEDs, plays a role in the early form. |
| Early HDN has been reported in newborns exposed in utero to
Phenobarbital, Primidone, Phenytoin, Carbamazepine, diazepam, and
Ethosuximide. |
|
| Breast feeding in Woman taking Antiepileptic drugs |
| Breast-feeding seems to prevent diarrhea and respiratory
illness, may reduce risk of some chronic diseases later in life. |
| AEDs are known to appear in breast milk in levels inversely
proportional to their degree of maternal serum protein binding. |
| AED concentrations in breast milk may be low, reduced
neonatal serum protein binding and slower rates of hepatic metabolism may result in serum
levels in the therapeutic range. |
| AED use by WWE does not constitute an absolute or automatic
contraindication to breast-feeding for their infants. |
| Women who choose to breast-feed their newborns should be
supported in their decision and counseled regarding the benefits of this form of infant
nutrition. |
| Need to inform them of possible infant sedation or feeding difficulties,
and uncertainty regarding the effect of AEDs on newborn growth and development. |
| The
potential for hematologic or hepatic toxicity appears to be small. |
Concentration of antiepileptic drugs in
breast milk expressed as percentage of maternal plasma concentration
| Antiepileptic drug |
Breast milk |
Reported adverse effect |
| Carbamazepine |
41 ± 16.8 |
|
| Ethosuximide |
94 ± 6 |
|
| Lamotrigine |
65 (48 h postpartum) |
|
| Phenobarbital |
36.1 ± 19.5 |
Sedation |
| Phenytoin |
18.6 ± 15.7 |
Methemoglobinemia |
| Primidone |
70.5 ± 29.2 |
Sedation, feeding difficulties |
| Valproate |
2.7 ± 1.5 |
Thrombocytopenic purpura |
|
| Further Reading |
|
Management issues for Women with Epilepsy (WWE), Zahn, CA. Morrell, MJ.
Collins, SD. Labiner, DM. Yerby, MS. Neurology.Vol 51 (4) 1998. |
| Yerby M, Collins S. Teratogenecity of antiepileptic
drugs. Engel J, Pedley T, editors. Epilepsy, a Comprehensive Textbook.
Philadelphia: Lippincott-Raven; 1997. p. 1195-1203 (84). |
| Guide for woman at childbearing age |
|
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