Maternal smoking during pregnancy is associated with a higher risk of non-syndromic orofacial clefts in infants: Is there an association between maternal tobacco smoking during pregnancy and nonsyndromic orofacial clefts in infants?

Data sourcesMedline and Embase were searched to 2002 using the search terms “cleft lip”, “cleft palate”, “smoking”, “tobacco”, “cigarette”, “mother” and “maternal”. Reference lists from retrieved articles and a monograph on neural tube defects were also examined for more studies.Study selectionCase–control and cohort studies that reported data on smoking by women during pregnancy were included. The outcomes were orofacial clefts (OFC) in infants, specifically cleft lip with or without cleft palate (CL±P) and cleft palate only (CP). Isolated or multiple defects were included, but syndromic cases were excluded wherever possible.Data extraction and synthesisMeta-analyses were carried out for CL±P, CP and total clefts. The analyses of CL±P and CP were repeated following stratification by the presence or absence of malformations in addition to the cleft, after the exclusion of studies that used malformed controls. Heterogeneity was assessed using the Q test and a random effect model was used if the P value was less than 0.1. Tests for publication bias and presence of a linear dose–response effect were also carried out when suitable data were available.ResultsThe search identified 32 articles, of which 24 met the inclusion criteria (15 case–control and nine cohort studies). Statistically significant associations were found between maternal smoking and CL±P (relative risk, 1.34; 95% confidence interval, 1.25–1.44), and between maternal smoking and CP (relative risk, 1.22; 95% confidence interval, 1.10–1.35). There was evidence of a modest dose–response effect for CL±P, but the evidence was not clear for CP. No strong evidence of publication bias could be found.ConclusionsThis study showed a consistent, moderate association between maternal tobacco smoking during pregnancy and nonsyndromic OFC in infants. The effect was observed for both isolated and multiple clefts, and was stronger and more consistent for CL±P than for CP.