Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society.
OBJECTIVE
To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid use, prenatal vitamin K use, risk of hemorrhagic disease of the newborn, clinical implications of placental and breast milk transfer of antiepileptic drugs (AEDs), risks of breastfeeding, and change in AED levels during pregnancy.


METHODS
A 20-member committee evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and October 2007.


RESULTS
Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in amounts that may be clinically important. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentration of lamotrigine, phenytoin, and to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative.


CONCLUSIONS
Supplementing women with epilepsy with at least 0.4 mg of folic acid before they become pregnant may be considered (Level C). Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered (Level B) and monitoring of levetiracetam and oxcarbazepine (as monohydroxy derivative) levels may be considered (Level C). A paucity of evidence limited the strength of many recommendations.
Harden
C L
CL
University of Miami, Miami, FL, USA.
Pennell
P B
PB
Koppel
B S
BS
Hovinga
C A
CA
Gidal
B
B
Meador
K J
KJ
Hopp
J
J
Ting
T Y
TY
Hauser
W A
WA
Thurman
D
D
Kaplan
P W
PW
Robinson
J N
JN
French
J A
JA
Wiebe
S
S
Wilner
A N
AN
Vazquez
B
B
Holmes
L
L
Krumholz
A
A
Finnell
R
R
Shafer
P O
PO
Le Guen
C
C
D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001942:Breast Feeding; D000013:Congenital Abnormalities / Q000453:epidemiology / Q000517:prevention & control*; D004827:Epilepsy / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D007231:Infant, Newborn; D008895:Milk, Human / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D012306:Risk; D014812:Vitamin K / Q000008:administration & dosage*; D006475:Vitamin K Deficiency Bleeding / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control
D000927:Anticonvulsants; D014812:Vitamin K; D005492:Folic Acid