TABLE 1 INCREASED RISKS OF PREGNANCY AND EPILEPSY
Effects on Epilepsy		Complications of Pregnancy		Complications in Offspring
Increased seizure frequency		Vaginal hemorrhage		Maldevelopment
		Microcephaly
Anemia		Anomalies
Declining drug levels Hyperemesisgravidarum		Malformations
		Death
Alteration of drug pharmacokinetics		Toxemia Stillbirth
		Neonatal death
Induced labor		Perinatal death
Prematurerupture of membranes		Hemorrhagic disease
		Others
Cesarean section		Low birth weight
		Prematurity
Seizures		Feeding difficulties
		Drug withdrawl Hypoxia

 

TABLE 2 EFFECT OF PREGNANCY ON SEIZURE FREQUENCY
	Percentage of Change in Seizure Frequency
Investigator		Increased	None	Decreased
Nerlinger 1889	--	36	12	36
Rubesca 1911	--	33	33	33
Baptisti 1938	34	24	62	15
Burnett 1946	19	42	53	6
Sabin & Oxorn 1956	55	33	52	15
Suter & Klingman 1957	93	46	46	8
Zlatkis 1966	43	75	16	9
Maroni & Markott 1969	31	24	73	3
Rosciszewska & Grudzinska 1970	29	24	28	48
Knight & Rhind 1975	84	45	50	5
Canger et al. 1982	--	41	50	9
Schmidt et al. 1983	136	37	50	13
Svigos 1984	74	24	--	--
Otani 1985	110	23	50	7
Vidovic & Della Marina, 1994	50	22	54	24
Sabers et al. 1998	151	21	--	--

Modified and updated from: Knight AH, Rhind EG. Epilepsy and pregnancy: A study of 153 pregnancies in 59 patients.
Epilepsia 1975;16:99. (Reprinted with permission from Raven Press.)

TABLE 3 PHARMACOKINETIC DATA
	Percent Decrease	Percent Free Fraction
Anticonvulsant	Total Level by 3rd Trimester	Normal	Maternal	Neonatal
Carbamazepine	40%	22%	25%	35%
Ethosuximide		90%	?	?
Phenobarbital	55%	51%	58%	66%
Phenytoin	56%	9%	11%	13%
Primidone	55%
Derived Phenobarbital	70%	75%	80%	?
Valproic Acid	50%	9%	15%	19%

TABLE 4 STILLBIRTH AND NEONATAL DEATH RATES IN INFANTS OF EPILEPTIC MOTHERS
	Stillbirths %		Neonatal Deaths %
Investigator	Cases	Controls	Cases	Controls
Janz 1964	12.1	7.0	1.3	---
Spiedel & Meadow 1972	1.3	1.2	2.7	1.0
Bjenkdal & Bahna 1973	5.3	7.8	3.2	1.5
Fedrick 1973		2.7	1.1 ---	---
Higgins & Comertond 1974	5.2	---	7.8	3.9
Knight & Rhind 1975	2.0	---	2.9	---
Nakane 1979	13.5	4.3	---	---
Nakane 1980	14.0	6.7	---	---
Nelson & Ellenberg 1982	5.1	1.9	3.5	2.7
Svigos 1984	0	1.3	0	1.3
Kalen 1986	2.2	---	---	2.7
Tanganelli & Regesta 1992	---	---	2.2	1.4

Table 5. Preconceptual Folate, after Lewis et al.
Authors	Study Type	N	Dose of Folate	Results
Smithells et al. 1983	Non-randomized, Controlled	Fully supplemented = 454 Partially supplemented = 519 Unsupplemented = 114	0.36 mg.	86 % risk reduction
Seller & Nevin 1984	Non-randomized	Unsupplemented = 543 Supplemented = 421	0.36 mg.	Risk reduction
Mulinare et al. 1988	Case-control	Case = 181 Control = 1480	Multivitamins with folate	60 % risk reduction
Milinsky et al. 1989	Cohort	23,491	"	71 % risk reduction
MRC 1991	Randomized, double blind, controlled	1195	4.0 mg.	72 % risk reduction
Czeizel & Dudas 1992	Randomized, controlled	Case = 2420 Control = 2333	0.8 mg.	No defects with folate supplementation
Werler et al. 1993	Case-control	Case = 436 Control = 2615	?	60 % risk reduction
Werler et al. 1996	Case-control	Case = 604 Control = 1658	Folate supplements	Folate did not decrease rates in women > 70kg.

Table 6 Breast Milk / Plasma Concentrations of AED
AED	Breast milk/ Plasma Concentration Ratio	Elimination 1/2 Life in Hours Adults	Elimination 1/2 Life in Hours Neonates
Carbamazepine	0.4 - 0.6	8 - 25	8 - 28
Ethosuximide	0.9	40 - 60	40
Phenobarbital	0.4 - 0.6	75 - 126	45 - 500
Phenytoin	0.2 - 0.4	12 - 50	15 - 105
Primidone	0.7 - 0.9	4 - 12	7 - 60
Valproic Acid	0.01	6 - 18	30 - 60
Gabapentine	?	5 - 8	?
Felbamate	?	14 - 22	?
Lamotrigine	> 1.0	24	?
Levetiracetam	?	6 - 8	?
Oxcarbazepine	?	8 - 10	?
Tiagabine	?	4 - 13	?
Topiramate	< 1.0	19 - 23	?
Zonisamide	0.9	50 - 60	?