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- Title
Risks of congenital malformations in offspring exposed to valproic acid in utero: A systematic review and cumulative meta-analysis.
- Authors
Tanoshima, M; Kobayashi, T; Tanoshima, R; Beyene, J; Koren, G; Ito, S
- Abstract
Despite extensive research efforts over decades, the teratogenic profile of valproic acid (VPA) remains obscure. We performed cumulative and conventional meta-analyses of cohort studies to determine the time profiles of signal emergence of VPA-associated congenital malformations (CMs) and to define risk estimates of each of the CMs. Fifty-nine studies were identified and analyzed. We found that the significant risk signals began to emerge over the last 10-20 years even before large-scale studies were performed: neural tube defect (the significant risk signal emerged in 1992); genitourinary and musculoskeletal anomalies (2004); cleft lip and/or palate (2005); and congenital heart defects (2006). At present, the risks of VPA-associated CMs are 2-7-fold higher than other common antiepileptic drugs. VPA should not be used as a first-line therapy in women of childbearing age unless it is the only option for the patient.
- Subjects
HUMAN abnormalities; VALPROIC acid; TREATMENT of musculoskeletal system abnormalities; ANTICONVULSANTS; META-analysis; DISEASE risk factors
- Publication
Clinical Pharmacology & Therapeutics, 2015, Vol 98, Issue 4, p417
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1002/cpt.158