Anti-epileptic medication during pregnancy


 


Several complications of pregnancy have been reported to occur more frequently in women with epilepsy than in the general population: vaginal hemorrhage (Bjerkedal and Bahna, 1973), placental abruption (Egenaes, 1982), pregnancy induced hypertension (Pritchard, Scott and Whalley, 1971), and intrauterine growth retardation [46, 47]. In the majority of reports it concerned trends without statistical significance being reached.


Several authors have referred to a relatively high intervention rate during the delivery of a pregnant woman with epilepsy. It concerns both induction of labor, delivery by forceps or vacuum extraction, and caesarean section (Yerby, Koepsell and Daling, 1985). Concerning the question why the intervention rate should be increased, little is known. Several authors believe that there is no rationale for an increase in interventions during delivery (Hiilesmaa, Bardy and Teramo, 1985). They suggest that mainly uncertainty in guiding the delivery of a woman with epilepsy accounts for the increased intervention rate in this group.


When receiving optimal care over 90% of women with epilepsy will have a successful pregnancy and a healthy child (Cleland, 1991). Optimal care implies pregnancy planning and close co-operation of obstetrician and neurologist (Allbert and Morrison, 1992). Except in the case of very severe epilepsy with poor seizure control there is no ground for advising against pregnancy (Hopskin, 1977).


AED-management throughout pregnancy faces a genuine dilemma (Lannon, 1994) On the one hand maternal epileptic seizures may cause fetal hypoxia and even fetal death, stressing the need for adequate seizure control with AEDs. On the other hand however, AEDs readily pass the placenta, enter the fetal circulation , and may adversely affect the child. Pregnant women with epilepsy should receive AED-therapy in the lowest possible dosage that provides adequate seizure control. In some cases, total discontinuation of AEDs may be an option. A decrease in AED-intake may especially be considered during critical periods in embryonal development. If possible, a single AED should be used instead of drug combinations. With the exception of trimethadion all AEDs may be considered. Remember that there is no AED that has not been implicated in teratology. AED-therapy should be continued during delivery. As oral treatment is likely to be hampered during the process of labor and delivery because of nausea and psychological tension, parenteral therapy is advisable in severe cases.


Primarily the patient’s clinical course should guide pharmacological management. Regular monitoring of AED-blood levels will provide additional information. In this respect, free blood levels are clearly to be preferred to total levels. Alternatively, total blood levels can be interpreted together with plasma albumin concentration. Some authors advise post-delivery determination of neonatal AED-blood levels.


Pregnant women with epilepsy should be offered an extensive ultrasonographic screening of the fetus for structural abnormalities. If valproate or carbamazepine is used, special attention should be paid to the neural tube. After delivery, the infant should be inspected for congenital abnormalities.


Seizures during pregnancy can best be controlled with a parenterally administered benzodiazepine as diazepam. The policy for status epilepticus is an energetic control of seizures with a benzodiazepine while maintaining adequate oxygenation. On the condition of careful antiepileptic surveillance, pregnancy may continue. Only if seizures cannot be controlled, termination of pregnancy may allow recovery.


In general breast feeding is not contraindicated. Mothers on antiepileptic drugs however tend to prefer formula feeding. This may particularly be true for mothers receiving phenobarbital or primidone because of the sedative effects of the medication passing to the infant through breast feeding.


In order to prevent AED-induced neonatal hemorrhage, related to a deficiency of the vitamin K-dependent clotting factors, all newborns of mothers with epilepsy should receive vitamin K :1 mg vitamin K1 orally or, for a more rapid effect, intramuscularly or intravenously. Many authors advise the additional prescription of vitamin K to the mother during the last weeks of pregnancy : 10–20 mg vitamin K1a day during the last 2–4 weeks of pregnancy and/or 10 mg intravenously during delivery. Reports on severe fetal hemorrhage following scalp sampling may be regarded as support for this practice. Umbilical cord blood should be investigated for clotting parameters. Treatment with fresh frozen plasma is indicated if vitamin K-dependent clotting factors are seriously decreased.


Many authors have advocated folic acid supplementation during a period ranging from preconceptional to 12 weeks gestational age. Whether women using AEDs need a higher dose of folic acid to prevent neural tube defects than do non-epileptic women is still unclear. Advice on folic acid supplementation for women using AEDs should not exceed an oral dose of 5 mg a day but probably a lower dose (0.5 – 1.0 mg a day) suffices [150]. Side effects of folic acid therapy are little but doses of over 5 mg a day could impair seizure control. Some authors reported on the phenytoin–folic acid interaction: phenytoin decreases the serum folate, whereas folic acid tends to lower serum phenytoin.


AED-induced enhancement of the microsomal enzyme system may cause a decrease of the vitamin D-blood level. Theoretically, fetal and neonatal bone mineralisation might be involved. Christiansen et al. studied biochemical indices of osteomalacia in pregnant women with epilepsy and in their offspring. The values obtained resembled those obtained for control-pregnant women and control-newborns. Christiansen et al. conclude that vitamin D-supplementation for mothers with epilepsy and their newborns is not indicated.


 


References


 


T. Bjerkedal and S.L. Bahna, The course and outcome of pregnancy in women with epilepsy. Acta Obstet Gynecol Scand 52 (1973), pp. 245–248.


 


Egenaes J. Outcome of pregnancy in women with epilepsy, Norway, 1967 to 1978: Complications during pregnancy and delivery. In: Janz D et al., editors. Epilepsy, Pregnancy and the Child; Raven Press, New York 1982; 81–5.


 


J.A. Pritchard, D.E. Scott and P.J. Whalley, Maternal folate deficiency and pregnancy wastage IV. Effects of folic acid supplements, anticonvulsants, and oral contraceptives. Am J Obstet Gynecol 109 (1971), pp. 341–346.


 


M.S. Yerby, N. Koepsell and J. Daling, Pregnancycomplications and outcomes in a cohort of women with epilepsy. Epilepsia 26 (1985), pp. 631–635.


 


V.K. Hiilesmaa, A. Bardy and K. Teramo, Obstetric outcome in women with epilepsy. Am J Obstet Gynecol 152 (1985), pp. 499–504.


 


P.G. Cleland, Risk-benefit assessment of anticonvulsants in women of child-bearing potential. Drug Safety 6 (1991), pp. 70–81.


 


J.R. Allbert and J.C. Morrison, Neurologic diseases in pregnancy. Obst Gynecol Clin North Am 19 (1992), pp. 765–781.


 


Hopkins A. The drug treatment of epilepsy in pregnancy. In: Lewis PJ [ed]. Therapeutic problems in pregnancy.MTP, Lancaster, 1977, 103.


 


S.L. Lannon, Epilepsy, pregnancy and parenting — an American perspective. Seizure 3 (1994), pp. 85–93.


 



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