Maternal cigarette smoking during pregnancy and risk of oral clefts in newborns

The results of previous epidemiologic research on the possible association between maternal smoking during pregnancy and risk of oral clefts in offspr ing have been inconsistent. This may be due in part to methodological limit ations, including imprecise measurement of tobacco use, failure to consider etiologic heterogeneity among types of oral clefts, and confounding. This analysis, based on a large case-control study, further evaluated the effect of first trimester maternal smoking on oral facial cleft risk by examining the dose-response relationship according to specific cleft type and accord ing to whether or not additional malformations were present. A number of fa ctors, including dietary and supplemental folate intake and family history of clefts, were evaluated as potential confounders and effect modifiers. Da ta on 3,774 mothers interviewed between 1976 and 1992 by the Slone Epidemio logy Unit Birth Defects Study were used. Study subjects were actively ascer tained from sites in areas around Boston, Massachusetts and Philadelphia, P ennsylvania; the state of Iowa; and southeastern Ontario, Canada. Cases wer e infants with isolated defects-cleft lip alone (n = 334), cleft lip and pa late (n = 494), or cleft palate alone (n = 244)-and infants with clefts plu s (+) additional malformations: cleft lip+ (n = 58), cleft lip and palate(n = 140), or cleft palate+ (n = 209). Controls were infants with defects o ther than clefts, excluding defects possibly associated with maternal cigar ette use. There were no associations with maternal smoking for any oral cle ft group, except for a positive dose response among infants with cleft lip and palate+ (for light smokers, odds ratio (OR) = 1.09 (95% confidence inte rval (CI): 0.6, 1.9); for moderate smokers, OR = 1.84 (95% CI: 1.2, 2.9); a nd for heavy smokers, OR = 1.85 (95% CI: 1.0, 3.5), relative to nonsmokers) . This finding may be related to the additional malformations rather than t o the cleft itself.