Italian Consensus Conference on Epilepsy and Pregnancy, Labor and Puerperium

Abstract

SUMMARYTo facilitate an integrated and rational approach to the care of women with epilepsy of childbearing potential, a group of experts appointed by Italian scientific societies in the fields of epileptology, neonatology, pediatrics, neuropediatrics, child neuropsychiatry, obstetrics, and gynecology held a joint meeting in Santa Trada di Cannitello, Reggio Calabria, Italy, on October [15][16] 2004, with the aim of reaching consensus on the optimal management of these women. An ad hoc system for the classification of available published evidence and the opinions of experts was developed and used to grade recommendations on different aspects related to counseling, diagnostic, and treatment issues. The present document summarizes available evidence on the reciprocal interactions between epilepsy, antiepileptic drugs, fertility, contraception, pregnancy, delivery, breastfeeding, and the offspring. Recommendations are made concerning the information and counseling that should be provided to women with epilepsy with respect to issues related to contraception, conception, pregnancy, labour, and puerperium. More detailed recommendations on the same issues are provided to physicians and other healthcare professionals involved in the care of these women, with special reference to choice of effective contraception, optimization of antiepileptic drug therapy, use of prenatal diagnostic tests and other monitoring procedures, and appropriate management practices in relation to childbirth, puerperium, and the care of the child. KEY WORDS: Epilepsy, Antiepileptic drugs, Fertility, Contraception, Pregnancy, Puerperium, Clinical management, Consensus paper, Italian League against Epilepsy.The management of women with epilepsy is complex and requires a multidisciplinary approach. However, there is currently no real coordination in Italy among the different professionals involved, and the advice given by the epileptologist will often differ from that given by the gynecologist, neonatologist, or pediatrician. As a result,

Antiepileptic Drug Interactions - Principles and Clinical Implications

“…The older enzyme-inducing AEDs and the newer, oxcarbazepine, lamotrigine, felbamate, topiramate (>200 mg), eslicarbazepine acetate, and rufinamide stimulate the metabolism of OCs involving CYP3A4. Women who use AEDs that interact with hormonal contraceptives (estrogen or gestagen) should be advised to use non-hormonal contraceptive methods [76] (Level 1 interactions).…”

“…Eslicarbazepine acetate (1200 mg daily) reduces the effectiveness of OCs, by a decrease of the AUC of levonorgestrel and ethinyloestradiol by 37% and 42%, respectively, due to enzyme induction [80] (Level 1 interaction, according to recent guidelines [76]).…”

“…This interaction is likely to be caused by stimulation of UGT1A4 activity by the steroids and may result in reduced seizure control in some women. The serum concentrations of lamotrigine should therefore be closely monitored, and this interaction is of major importance, as lamotrigine is often a preferred choice of drug in female patients (Level 1 interaction, according to [76]). Rifampicin has been shown to increase lamotrigine clearance of about 50 % [103].…”

Maternal epilepsy and adverse pregnancy outcomes

“…The American Academy of Neurology recommends at least 0.4 mg per day [44], while the UK NICE guidelines recommend all women on AEDs to be offered 5 mg of folic acid daily before any possibility of pregnancy [101]. In Norway [45], Denmark [46] and Italy [47], women with epilepsy and AED use are advised to take at least 0.4 mg of folic acid per day before conception and early in pregnancy, but 4-5 mg per day if they are using older AEDs such as valproic acid and carbamazepine. Wald et al systematically reviewed ingested folate dose, resulting serum concentrations and influence on neural tube defects.…”

“…Uncertainty, together with misperception of an increased complication risk, may account for the high rates. The UK NICE guidelines, the American Academy of Neurology Practice Parameter update and the Italian Consensus Conference recommend vaginal delivery in women with epilepsy, with the exception of women with frequent seizures [47,68,101].…”