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Are antiepileptic drugs necessary? What effect do antiepileptic drugs have on the fetus? What effect does maternal epilepsy have on the fetus? What effect does pregnancy have on seizures? How should the patient be managed during pregnancy and delivery? How should the patient be managed during the postpartum period?
OBSTETRICAL COMPLICATIONS A number of obstetrical complications are reported to be more common in women with epilepsy; these range from mild to severe, and include a low birth weight, lower Apgar scores, preeclampsia, bleeding, placental abruption, and prematurity
Perinatal mortality and miscarriage The rates of stillbirth, neonatal death, and perinatal death vary widely and have been reported to be as high as two to three times greater in infants born to women with epilepsy
The mechanism of this risk is not well understood. In one study, the investigators found an increased risk of spontaneous abortion for both fathers and mothers with epilepsy compared with same-sex siblings
There is an increased risk of both major and minor malformations in fetuses exposed to the AEDs. The reported risk of major fetal malformations in women taking AEDs is 4 to 6 percent, compared with a population estimate of 2 to 3 percent
AEDs Teratogenisity Major malformations: Cleft lip & Cleft palate Cardiac defects (VSD) Neural tube defect Urogenital defects Minor malformations: Hypertlorism, Epicantal folds Prominent lips Fingernail hypoplasia Upward nasal tip
The following recommendations are proposed as guidelines: The choice of AED for WWE during their reproductive years should be that deemed most appropriate for seizure type. Monotherapy should be the aim of treatment.
The decrease in effectiveness of hormonal contraception observed in WWE taking enzyme-inducing AEDs must be discussed with all WWE as they enter reproductive years.
In light of known pregnancy patterns (high rate of unplanned pregnancies and late provider contact), folic acid supplementation should be instituted in WWE with no less than 0.4 mg per day and continued through pregnancy.
Folic Acid Patients taking valproate or carbamazepine should receive daily folic acid supplementation (4 mg/day) for one to three months prior to conception. Women who are taking other AEDs should take the more standard lower dose of folic acid (0.4 to 0.8 mg per day)
The following recommendations are proposed as practice options: If hormonal contraception is chosen as the preferred method of birth control in a woman taking enzyme-inducing AEDs, a formulation that includes at least 50 μg of ethinyl estradiol or mestranol should be used. The risk of contraceptive failure in this setting should be discussed with WWE and the discussion documented.
prepregnancy and pregnancy folic acid supplementation; teratogenic potential of AEDs, including risk levels and discussion of major and minor birth defects;
Options for considering AED discontinuation before pregnancy; Possibility for change in seizure frequency during pregnancy;
Importance of medication compliance during pregnancy; Need for regular follow-up during pregnancy with AED level monitoring;
Inheritance risks for seizures; Vitamin K supplementation in the last month of pregnancy; and advantages and disadvantages of breast-feeding.
The following recommendations are proposed as guidelines: AED therapy for WWE should be optimized before conception if possible.
If AED withdrawal is planned, this should be completed at least 6 months before conception. Change to an alternate AED should not be undertaken during pregnancy for the sole purpose of reducing teratogenic risk.
WWE, especially those treated with carbamazepine, divalproex sodium, or valproic acid, should be offered prenatal testing with alpha-fetoprotein levels at 14 to 16 weeks gestation, Level II (structural) ultrasound at 16 to 20 weeks gestation, and, if appropriate, amniocentesis for amniotic fluid alphafetoprotein and acetylcholinesterase levels.
Long-term effects Reports from studies implicate phenytoin, carbamazepine, pri midone, and phenobarbital exposures with impaired cognitive performance later in life. Sodium valproate: verbal IQ, autism
Breast-feeding is not contraindicated in WWE taking AEDs; however, for WWE taking sedating AEDs, the neonate must be monitored for sedation.
. Most experts believe that taking AEDs does not generally contraindicate breast feeding, as probable benefits outweigh risk
Problems tend to occur only with the sedative drugs, such as phenobarbital, primidone, or benzodiazepines. Exposure to these drugs may cause the child to become irritable, fall asleep shortly after beginning to nurse, or fail to thrive. If this occurs, breast feeding may need to be discontinued but can be retried one week later.
One of the newer AEDs, lamotrigine, can be excreted extensively in breast milk. One study in 30 infants found that mild/plasma concentrations were highly variable, but that overall, lamotrigine exposure during lactation is at most marginally higher than that of other AEDs and as with all other AEDS, considerably less than placental transfer. No adverse events in these infants were observed in the first postnatal year.
Small studies of levetiracetam, topiramate, and gabapentin have found that while present in breast milk in concentrations similar to maternal plasma, the concentrations in infant plasma were low, suggesting rapid elimination
Neurodevelopmental outcomes at age three years were examined in 199 children exposed to either carbamazepine, lamotrigine, phenyto in, or valproate in utero; IQs for breastfed children did not differ from nonbreastfed children for all AEDs combined and for each of four individual AED groups.
The following recommendations are proposed as practice options: Non protein-bound AED levels should be monitored during pregnancy. For the stable patient, levels should be ascertained before conception, at the beginning of each trimester, and in the last month of pregnancy. Additional levels should be done when clinically indicated (seizure occurrence, side effects, suspected noncompliance).
AED levels should be monitored through the eighth postpartum week. If AED dosage increases have been necessary during pregnancy, subsequent reductions to the prepregnancy dosage will usually be possible and may be necessary to avoid toxicity.
Vitamin K, 10 mg per day, should be prescribed in the last month of pregnancy to WWE taking enzyme-inducing AEDs. If this has not been done, parenteral vitamin K1 should be administered to WWE as soon as possible after the onset of labor. Note: This recommendation does not supplant the ACOG/AAP recommendation for the administration of 1 mg vitamin K1 to the neonate.