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Risks of congenital malformations in offspring exposed to valproic acid in utero : A systematic review and cumulative meta‐analysis
Author(s) -
Tanoshima M,
Kobayashi T,
Tanoshima R,
Beyene J,
Koren G,
Ito S
Publication year - 2015
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.158
Subject(s) - in utero , offspring , valproic acid , meta analysis , medicine , congenital malformations , pregnancy , obstetrics , physiology , epilepsy , biology , fetus , genetics , psychiatry
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.