Oral Clefts and maternal smoking associated suggests review

shutterstock_91019771 Clefts

Oral Clefts are common birth defects with incidence ranging from 1-2.2 per 1000 births in different parts of the world. Oral clefts can be divided into cleft lip with or without cleft palate (CL± P) and cleft palate only (CP), according to differences in anatomy, genetics, and embryology. They can be further classified as; isolated-clefts that occur alone or with secondary or minor defects; multiple, clefts with other major defects not recognized as syndromes; syndromes-clefts with other major defects that are recognized as syndromes.

The aim of this review was to assess the association between maternal active smoking during pregnancy, especially in the first trimester, and the incidence of cleft lip and palate in their offspring.


Searches were conducted in the Cochrane, PubMed, and Ovid Medline databases. Case-control and cohort studies with records of maternal active smoking (includinglevels of exposure) before and after conception, especially the peri-conception period were considered. Reviewers defined the peri-conception period as the period from 3 months before conception to the first trimester of pregnancy. Odds ratio (OR) and associated 95% confidence interval (CI) were calculated from raw data from each study.Random effects meta-analysis were conducted for total clefts, CL  ± P, and CP, as well as isolated CL±  P and CP, if available. Total cleft cases were only analyzed when CL ± P and CP were not distinguished.


  • 23 case-control studies and 6 cohort studies were
  • Meta-analysis suggests that maternal smoking around conception and during pregnancy has a moderately positive association with CLP and CP.
  Odds ratio (95% CI)
Total clefts 1.399  (1.258-1.556)
Cleft lip with or without cleft palate 1.368  (1.259-1.486)
Isolated CL P 1.315  ( 1.200-1.442)
Cleft palate only 1.241   (1.117-1.378)
Isolated Cleft palate 1.326  (1.202-1.462)


The authors concluded

There is a moderate risk for having a child with a CL ± P or CP in women who smoke during pregnancy. We could not confirm whether there was a positive dose-response effect between maternal smoking and clefts.


Three major databases were searched but it was not clear if the search was limited in respect of publication date or language.  No details were provided regarding how study selection and data abstraction was carried out. There was also no formal assessment of study quality.  Smoking ‘dose ‘ classification varied in the study so it would have been helpful to understand how this was assessed in the original studies and whether there were specific inclusion criteria in relation to this as there is likely to be an impact of reporting bias as noted in the authors discussion.  A earlier review by Sabbagh et al (Dental Elf – 24th Mar 2015) also suggested a link between maternal passive smoking and non-syndromic orofacial clefts.


Primary paper

Xuan Z, Zhongpeng Y, Yanjun G, Jiaqi D, Yuchi Z, Bing S, Chenghao L. Maternal active smoking and risk of oral clefts: a meta-analysis. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016 Aug 18. pii: S2212-4403(16)30292-9.doi: 10.1016/j.oooo.2016.08.007. [Epub ahead of print] Review. PubMed PMID: 27727103.

Other references

Dental Elf – 24th Mar 2015

Passive smoking: linked with non-syndromic orofacial clefts




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Derek Richards

Derek Richards is a specialist in dental public health, Director of the Centre for Evidence-Based Dentistry and Specialist Advisor to the Scottish Dental Clinical Effectiveness Programme (SDCEP) Development Team. A former editor of the Evidence-Based Dentistry Journal and chief blogger for the Dental Elf website until December 2023. Derek has been involved with a wide range of evidence-based initiatives both nationally and internationally since 1994. Derek retired from the NHS in 2019 remaining as a part-time senior lecturer at Dundee Dental School until the end of 2023.

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