Dp. Lewis et al., DRUG AND ENVIRONMENTAL-FACTORS ASSOCIATED WITH ADVERSE PREGNANCY OUTCOMES PART I - ANTIEPILEPTIC DRUGS, CONTRACEPTIVES, SMOKING, AND FOLATE, The Annals of pharmacotherapy, 32(7-8), 1998, pp. 802-817
OBJECTIVE: Part I Of this review examines the relationship between ant
iepileptic drugs (AEDs) and pregnancy outcomes. Drug-induced folate de
ficiency and the role of AED metabolism are emphasized. Part II will d
iscuss periconceptional folate supplementation for prevention of birth
defects. Part III will discuss the mechanism of folate's protective e
ffect, therapeutic recommendations, compliance, and cost. DATA SOURCES
: A MEDLINE search was conducted for journal articles published throug
h December 1997. Additional sources were obtained from Current Content
s and citations from the references obtained. Search terms included ph
enytoin, carbamazepine, phenobarbital, primidone, valproic acid, oral
contraceptives, clomiphene, drug-induced abnormalities, spina bifida,
anencephaly, neural tube defect, folate, folic acid and folic acid def
iciency. STUDY SELECTION: Relevant animal and human studies examining
the effects of AEDs, smoking, and oral contraceptives on folate status
and pregnancy outcome are reviewed. DATA EXTRACTION: Studies and case
reports were interpreted. Data extracted included dosing, serum and r
ed blood cell folate concentrations, teratogenicity of anticonvulsant
medications, metabolism of AEDs and folate, and genetic susceptibility
to AED-induced teratogenicity. DATA SYNTHESIS: Low serum and red bloo
d cell folate concentrations are associated with adverse pregnancy out
comes. Decreases in serum folate are seen with AEDs, oral contraceptiv
es, and smoking. Since similar birth defects are observed with multipl
e AEDs, metabolism of aromatic AEDs to epoxide metabolites and genetic
factors may play a role in teratogenesis. CONCLUSIONS: Adequate prepr
egnancy planning is essential for women who have epilepsy. Women recei
ving folate-lowering drugs may be at increased risk of adverse pregnan
cy outcomes. Therefore, epileptic women contemplating pregnancy should
be treated with the minimum number of folate-lowering drugs possible
and receive folic acid supplementation.