Benzodiazepine use in pregnancy and major malformations or oral cleft: meta-analysis of cohort and case-control studies. Issue 7162 (26th September 1998)

• Record Type: Journal Article
• Authors: Dolovich, Lisa R; Addis, Antonio; Vaillancourt, J M Régis; Power, J D Barry; Koren, Gideon; Einarson, Thomas R
• Is Part Of: BMJ. Volume 317:Issue 7162(1998)
• Page Start: 839
• Page End: 843
• Publication Date: 1998-09-26
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Medicine; Periodicals; 610
• DOI: 10.1136/bmj.317.7162.839
• Languages: English
• ISSNs: 0007-1447

Abstract

Abstract: Objective: To determine if exposure to benzodiazepines during the first trimester of pregnancy increases risk of major malformations or cleft lip or palate. Design Meta-analysis. Setting: Studies from 1966 to present. Subjects: Studies were located with Medline, Embase, Reprotox, and from references of textbooks, reviews, and included articles. Included studies were original, concurrently controlled studies in any language. Interventions: Data extraction and quality assessment were done independently and in duplicate. Main outcome measures: Maternal exposure to benzodiazepines in at least the first trimester; incidence of major malformations or oral cleft alone, measured as odds ratios and 95% confidence intervals with a random effects model. Results: Of over 1400 studies reviewed, 74 were retrieved and 23 included. In the analysis of cohort studies fetal exposure to benzodiazepine was not associated 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-control studies showed an association between exposure to benzodiazepines and development of major malformations (3.01; 1.32 to 6.84) or oral cleft alone (1.79; 1.13 to 2.82). Conclusions: Pooled data from cohort studies showed no association between fetal exposure to benzodiazepines and the risk of major malformations or oral cleft. On the basis of pooled data from case-control studies, however, there was a significant increased risk for major malformations or oral cleft alone. Until more research is reported, level 2 ultrasonography should be used to rule out visible forms of cleft lip.