Epilepsy and Pregnancy Epilepsy and Pregnancy Interaction between - PowerPoint PPT Presentation

6/11/2010 Epilepsy and Pregnancy Epilepsy and Pregnancy � Interaction between disease and pregnancy � Interaction between disease and pregnancy Yasser Y. El Yasser Y. El-Sayed, M.D. Sayed, M.D. � Teratogenic risks of Antiepileptic Drugs (AED) � Teratogenic risks of Antiepileptic Drugs (AED) Professor and Associate Chief Professor and Associate Chief Division of Maternal Division of Maternal-Fetal Medicine and Obstetrics Fetal Medicine and Obstetrics � � Management guidelines Management guidelines Department of Obstetrics & Gynecology Department of Obstetrics & Gynecology Stanford University School of Medicine Stanford University School of Medicine Seizure Classification Scope of the Problem � Focal Seizures � Focal Seizures � Generalized Seizures � Generalized Seizures � Simple Partial � Simple Partial � Absence � Absence � � Tonic Tonic � � Complex Partial Complex Partial � Clonic � Clonic � In U.S. 1.1 million women with epilepsy are in their � In U.S. 1.1 million women with epilepsy are in their � � Toni Toni- -Clonic Clonic � Secondary Generalized � Secondary Generalized active reproductive years active reproductive years � � Myoclonic Myoclonic � � Atonic Atonic � � Epilepsy affects 0.5 to 1% of pregnant women. Epilepsy affects 0.5 to 1% of pregnant women. Antiepileptic Drugs Antiepileptic Drugs Traditional Traditional Newer Newer � Most frequently encountered neurologic condition Most frequently encountered neurologic condition � � Ethosuximide � Ethosuximide Gabapentin Gabapentin in obstetric practice after migraine in obstetric practice after migraine � Valproate � Valproate Lamotrigine Lamotrigine � � Phenobabrbitol Phenobabrbitol Topiramate Topiramate � � Carbamezapine Carbamezapine Tiagabine Tiagabine � 80% of pregnant women with epilepsy use � 80% of pregnant women with epilepsy use � � Mysoline Mysoline Levetiracetam Levetiracetam antiepileptic drugs antiepileptic drugs � � Phenytoin Phenytoin Oxcarbazepine Oxcarbazepine Zonisamide Zonisamide LaRoche et al JAMA 2004 LaRoche et al JAMA 2004 1

6/11/2010 Contributing Factors � Older reports: up to 75% of women experience Older reports: up to 75% of women experience � increased seizure frequency increased seizure frequency � � High levels of estrogen High levels of estrogen � Increased nausea and vomiting � Increased nausea and vomiting � Recent reports: 15% of experience reduced Recent reports: 15% of experience reduced � � Changes in plasma volume Changes in plasma volume � � � Altered gastric motility Altered gastric motility seizure control seizure control � � Altered protein binding Altered protein binding � Increased metabolic capacity of the maternal liver � Increased metabolic capacity of the maternal liver � Possible risk factor: High seizure frequency Possible risk factor: High seizure frequency � � � Placental/Fetal Metabolism Placental/Fetal Metabolism antedating pregnancy antedating pregnancy � Poor compliance Poor compliance � � � Increased life stressors Increased life stressors Seizures in Pregnancy � � Tonic Tonic-clonic convulsion clonic convulsion � Profound alterations in maternal acid � Profound alterations in maternal acid-base base � Blood pressure elevated � Blood pressure elevated equilibrium with grand mal seizure equilibrium with grand mal seizure � Redistribution of blood flow to brain and � Redistribution of blood flow to brain and � Maternal serum lactate concentration may � Maternal serum lactate concentration may muscles, and away from visceral organs muscles, and away from visceral organs rise 10 fold, pH drop as low as 6.9 rise 10 fold, pH drop as low as 6.9 � Increased intra � Increased intra-abdominal pressure abdominal pressure � Changes in maternal acid � Changes in maternal acid-base equilibrium base equilibrium reduces uterine circulation further reduces uterine circulation further rapidly mediated through placenta to fetus rapidly mediated through placenta to fetus 2

6/11/2010 � � Maternal Mortality Maternal Mortality � � Maternal Trauma from Seizure activity Maternal Trauma from Seizure activity � In U.K. 1985 � In U.K. 1985-1999: 1000 deaths from 11 1999: 1000 deaths from 11 million pregnancies million pregnancies � Term with grand mal seizure Term with grand mal seizure � � 50 of these deaths were to women with epilepsy � 50 of these deaths were to women with epilepsy � Fracture of left acetabulum Fracture of left acetabulum � (WWE) (WWE) � Subsequent seizure resulted in right Subsequent seizure resulted in right � � Most of these deaths seizure related � Most of these deaths seizure related acetabular fracture and fracture of left acetabular fracture and fracture of left proximal humerus proximal humerus Ovesen J et al. Ugeskr Laeger 1998 Ovesen J et al. Ugeskr Laeger 1998 � � Epilepsy third most common cause of indirect Epilepsy third most common cause of indirect death in pregnancy (behind cardiac deaths and death in pregnancy (behind cardiac deaths and stroke). stroke). Barrett and Richens. Epilepsy Research. 2003. Barrett and Richens. Epilepsy Research. 2003. � Fetal Consequences Fetal Consequences � � Single brief tonic Single brief tonic-clonic seizure clonic seizure � � Depression of fetal heart rate for more than 20 � Depression of fetal heart rate for more than 20 � Bradycardia � Bradycardia minutes minutes Teramo et al. J. Perinat Med 1979 Teramo et al. J. Perinat Med 1979 � � Complex partial seizure during labor Complex partial seizure during labor � � Acidosis Acidosis � Prolonged uterine contraction and 3.5 minutes Prolonged uterine contraction and 3.5 minutes � fetal bradycardia fetal bradycardia Nei et al. Neurology 1998 Nei et al. Neurology 1998 � � Abruption Abruption � Recurrent maternal epileptic seizures � Recurrent maternal epileptic seizures � � Stillbirth Stillbirth � � Fetal intracranial hemorrhage and Fetal intracranial hemorrhage and hydrocephalus hydrocephalus Ohba et al. J Mat-Fet Invest 1998 Ohba et al. J Mat Fet Invest 1998 3

6/11/2010 Epilepsy: Perinatal Complications � � Status Epilepticus Status Epilepticus � � One seizure that lasts 30 minutes or more OR a One seizure that lasts 30 minutes or more OR a � � Preeclampsia Preeclampsia series of very closely spaced seizures, without series of very closely spaced seizures, without regaining consciousness regaining consciousness � Maternal hemorrhage � Maternal hemorrhage � Placental abruption � Placental abruption � Cesarean delivery Cesarean delivery � � Up to 1.8% incidence in pregnancy � Up to 1.8% incidence in pregnancy � 30 30-50% risk of fetal death 50% risk of fetal death � � Preterm delivery � Preterm delivery � Risk of maternal trauma, aspiration, brain Risk of maternal trauma, aspiration, brain � � Intrauterine growth restriction � Intrauterine growth restriction damage and death damage and death � Higher incidence during the third trimester Higher incidence during the third trimester � Microcephaly and mental retardation Microcephaly and mental retardation � � � � Congenital malformations Congenital malformations � � Perinatal mortality Perinatal mortality � � Population based cohort study in Norway1995 Population based cohort study in Norway1995-2005 2005 � � Preeclampsia and hemorrhage double unmatched Preeclampsia and hemorrhage double unmatched control group, and increased risk of preterm labor control group, and increased risk of preterm labor � � 2,805 WWE vs. 362,302 without epilepsy 2,805 WWE vs. 362,302 without epilepsy Bjerkedal and Bahna. Acta Obstet Gynecol Scand 1973 Bjerkedal and Bahna. Acta Obstet Gynecol Scand 1973 � � WWE on AED WWE on AED � � Increased risks of stillbirth, microcephaly and Increased risks of stillbirth, microcephaly and � Mild preeclampsia (1.3 Mild preeclampsia (1.3-2.4) 2.4) � mental retardation mental retardation � Gestational Hypertension (1.0 Gestational Hypertension (1.0-2.2) 2.2) � Nelson and Ellenberg. Neurology 1982 Nelson and Ellenberg. Neurology 1982 � Bleeding (1.1 Bleeding (1.1-3.2) 3.2) � � PTD <34 weeks (1.1 PTD <34 weeks (1.1-2.0) 2.0) � 204 births to epileptic mothers to 612 unmatched 204 births to epileptic mothers to 612 unmatched � � controls - 2.8 fold risk low birth weight, 3.7 fold controls 2.8 fold risk low birth weight, 3.7 fold risk low APGAR scores or asphyxia risk low APGAR scores or asphyxia � � No difference for WWE not on AEDs No difference for WWE not on AEDs Yerby et al. Epilepsia. 1985 Yerby et al. Epilepsia. 1985 Borthen et al. BJOG. 2009 Borthen et al. BJOG. 2009 4