Background: The association between maternal tobacco smoke exposure and the occurrence of orofacial clefts (OFCs) is evident from several meta-analyses; however, a review of these findings is lacking.
Objective: To review the evidence in the literature systematically for the main findings of these meta-analyses.
Material and Method: A systematic literature search between 1966 and 2016 was conducted through PubMed, using the search terms ‘cleft lip palate’ or ‘orofacial clefts’, and ‘tobacco smoke’.
Results: Based on a meta-analysis of 14 studies, passive tobacco smoke exposure increased the risk of non-syndromic
orofacial clefts (NSOFC) 2.11 times (odds ratio [OR] (95% confidence interval [CI]: 1.54-2.89). A pooled analysis of 2
studies, however, revealed no association between passive tobacco smoke exposure and the risk of OFCs (OR: 1.09 [95% CI: 0.93–1.27]). Two meta-analyses comprising a respective 38 and 5 studies found significant positive associations between
active tobacco smoke exposure and the occurrence of OFCs (OR: 1.28 [95% CI: 1.20-1.36]) and NSOFC (OR: 1.64 [95%
CI: 1.33-2.02]), respectively.
Conclusion: The current systematic review of reported meta-analyses revealed a positive association between maternal
smoke exposure and an increased risk of occurrence of OFCs and NSOFC. These findings confirm that pregnant women
should avoid tobacco smoke.

Keywords: Tobacco smoke exposure, Non-syndromic orofacial clefts, Orofacial clefts, Meta-analysis, Systematic review,
Pregnant woman