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Drug and environmental factors associated with adverse pregnancy outcomes. Part I: Antiepileptic drugs, contraceptives, smoking, and folate.

Abstract

OBJECTIVE

Part I of this review examines the relationship between antiepileptic drugs (AEDs) and pregnancy outcomes. Drug-induced folate deficiency and the role of AED metabolism are emphasized. Part II will discuss periconceptional folate supplementation for prevention of birth defects. Part III will discuss the mechanism of folate's protective effect, therapeutic recommendations, compliance, and cost.

DATA SOURCES

A MEDLINE search was conducted for journal articles published through December 1997. Additional sources were obtained from Current Contents and citations from the references obtained. Search terms included phenytoin, carbamazepine, phenobarbital, primidone, valproic acid, oral contraceptives, clomiphene, drug-induced abnormalities, spina bifida, anencephaly, neural tube defect, folate, folic acid, and folic acid deficiency.

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 red 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 blood cell folate concentrations are associated with adverse pregnancy outcomes. Decreases in serum folate are seen with AEDs, oral contraceptives, and smoking. Since similar birth defects are observed with multiple AEDs, metabolism of aromatic AEDs to epoxide metabolites and genetic factors may play a role in teratogenesis.

CONCLUSIONS

Adequate prepregnancy planning is essential for women who have epilepsy. Women receiving folate-lowering drugs may be at increased risk of adverse pregnancy outcomes. Therefore, epileptic women contemplating pregnancy should be treated with the minimum number of folate-lowering drugs possible and receive folic acid supplementation.

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  • Authors+Show Affiliations

    ,

    College of Pharmacy, University of Iowa, Iowa City 52242, USA.

    , ,

    Source

    MeSH

    Anticonvulsants
    Contraceptive Agents
    Drug Interactions
    Drug-Related Side Effects and Adverse Reactions
    Environmental Exposure
    Environmental Pollutants
    Female
    Folic Acid
    Humans
    Neural Tube Defects
    Pregnancy
    Pregnancy Complications
    Pregnancy Outcome
    Smoking

    Pub Type(s)

    Journal Article
    Research Support, U.S. Gov't, P.H.S.
    Review

    Language

    eng

    PubMed ID

    9681097

    Citation

    Lewis, D P., et al. "Drug and Environmental Factors Associated With Adverse Pregnancy Outcomes. Part I: Antiepileptic Drugs, Contraceptives, Smoking, and Folate." The Annals of Pharmacotherapy, vol. 32, no. 7-8, 1998, pp. 802-17.
    Lewis DP, Van Dyke DC, Stumbo PJ, et al. Drug and environmental factors associated with adverse pregnancy outcomes. Part I: Antiepileptic drugs, contraceptives, smoking, and folate. Ann Pharmacother. 1998;32(7-8):802-17.
    Lewis, D. P., Van Dyke, D. C., Stumbo, P. J., & Berg, M. J. (1998). Drug and environmental factors associated with adverse pregnancy outcomes. Part I: Antiepileptic drugs, contraceptives, smoking, and folate. The Annals of Pharmacotherapy, 32(7-8), pp. 802-17.
    Lewis DP, et al. Drug and Environmental Factors Associated With Adverse Pregnancy Outcomes. Part I: Antiepileptic Drugs, Contraceptives, Smoking, and Folate. Ann Pharmacother. 1998;32(7-8):802-17. PubMed PMID: 9681097.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Drug and environmental factors associated with adverse pregnancy outcomes. Part I: Antiepileptic drugs, contraceptives, smoking, and folate. AU - Lewis,D P, AU - Van Dyke,D C, AU - Stumbo,P J, AU - Berg,M J, PY - 1998/7/29/pubmed PY - 1998/7/29/medline PY - 1998/7/29/entrez SP - 802 EP - 17 JF - The Annals of pharmacotherapy JO - Ann Pharmacother VL - 32 IS - 7-8 N2 - OBJECTIVE: Part I of this review examines the relationship between antiepileptic drugs (AEDs) and pregnancy outcomes. Drug-induced folate deficiency and the role of AED metabolism are emphasized. Part II will discuss periconceptional folate supplementation for prevention of birth defects. Part III will discuss the mechanism of folate's protective effect, therapeutic recommendations, compliance, and cost. DATA SOURCES: A MEDLINE search was conducted for journal articles published through December 1997. Additional sources were obtained from Current Contents and citations from the references obtained. Search terms included phenytoin, carbamazepine, phenobarbital, primidone, valproic acid, oral contraceptives, clomiphene, drug-induced abnormalities, spina bifida, anencephaly, neural tube defect, folate, folic acid, and folic acid deficiency. 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 red 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 blood cell folate concentrations are associated with adverse pregnancy outcomes. Decreases in serum folate are seen with AEDs, oral contraceptives, and smoking. Since similar birth defects are observed with multiple AEDs, metabolism of aromatic AEDs to epoxide metabolites and genetic factors may play a role in teratogenesis. CONCLUSIONS: Adequate prepregnancy planning is essential for women who have epilepsy. Women receiving folate-lowering drugs may be at increased risk of adverse pregnancy outcomes. Therefore, epileptic women contemplating pregnancy should be treated with the minimum number of folate-lowering drugs possible and receive folic acid supplementation. SN - 1060-0280 UR - https://www.unboundmedicine.com/medline/citation/9681097/full_citation L2 - http://journals.sagepub.com/doi/full/10.1345/aph.17297?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -