Maternal Cigarette Smoking and Cleft Lip and Palate: A Systematic Review and Meta-Analysis

Objectives A systematic review and meta-analysis to determine the association between active maternal smoking and cleft lip and palate etiology. Data sources Medline, Embase, Web of Science and the Cochrane Library from inception to November, 2020. Study selection Observational studies of cigarette smoking habits in pregnant women. Outcomes included cleft lip and/or palate, cleft lip +/- palate and cleft palate only. Data analysis Publication bias analyses were performed and the Newcastle Ottawa scales were used to assess study quality. Fixed or random effect models were used in the meta-analysis, dependent on risk of statistical heterogeneity. Results Forty-five studies were eligible for inclusion of which 11 were cohort and 34 were case-control studies. Sixteen studies were of sufficient standard for inclusion in the meta-analysis. The summary odds ratio for the association between smoking and cleft lip and/or palate was 1.42 (95%CI 1.27-1.59) with a population attributable fraction of 4% (95%CI 3%-5%). There was limited evidence to show a dose-response effect of smoking. Conclusions This review reports a moderate association between maternal smoking and orofacial cleft but the overall quality of the conventional observational studies included was poor. There is a need for high quality and novel research strategies to further define the role of smoking in the etiology of cleft lip and palate.