BENZODIAZEPINE USE IN PREGNANCY AND MAJOR MALFORMATIONS OR ORAL CLEFT- METAANALYSIS OF COHORT AND CASE-CONTROL STUDIES

Objective: To determine if exposure to benzodiazepines during the firs t trimester of pregnancy increases risk of major malformations or clef t lip or palate.Design: Meta-analysis. Setting: Studies from 1966 to p resent Subjects: Studies were located with Medline, Embase, Reprotox, and from references of textbooks, reviews, and included articles. Incl uded studies were original, concurrently controlled studies in any lan guage. Interventions: Data extraction and quality assessment were done independently and in duplicate. Main outcome measures: Maternal expos ure to benzodiazepines in at least the first trimester; incidence of m ajor malformations or oral cleft alone, measured as odds ratios and 95 % confidence intervals with a random effects model. Results: Of over 1 400 studies reviewed, 74 were retrieved and 23 included. In the analys is of cohort studies fetal exposure to benzodiazepine was not associat ed with major malformations (odds ratio 0.90; 95% confidence interval 0.61 to 1.35) or oral cleft (1.19; 0.34 to 4.15). Analysis of case-con trol studies showed an association between exposure to benzodiazepines and development of major malformations (3.01; 1.32 to 6.84) or oral c left alone (1.79; 1.13 to 2.82). Conclusions: Pooled data fk om cohort studies showed no association between fetal exposure to benzodiazepin es and the risk of major malformations or oral cleft On the basis of p ooled data from case-control studies, however, there was a significant increased risk for major malformations or oral cleft alone. Until mor e research is reported, level 2 ultrasonography should be used to rule out risible forms of cleft lip.