Interaction between smoking and body mass index and risk of oral clefts

Abstract

PurposeTo examine maternal smoking and body mass index (BMI) interactions in contributing to risk of oral clefts. MethodsWe studied 4935 cases and 10,557 controls from six population-based studies and estimated a pooled logistic regression of individual-level data, controlling for study fixed effects and individual-level risk factors. ResultsWe found a significant negative smoking–BMI interaction, with cleft risk with smoking generally declining with higher BMI. For all clefts combined, the odds ratio for smoking was 1.61 (95% confidence interval [CI]: 1.39–1.86) at BMI 17 (underweight), 1.47 (95% CI: 1.34–1.62) at BMI 22 (normal weight), 1.35 (95% CI: 1.22–1.48) at BMI 27 (overweight), 1.21 (95% CI: 1.04–1.41) at BMI 33 (obese), and 1.13 (95% CI: 0.92–1.38) at BMI 37 (very obese). A negative interaction was also observed for isolated clefts and across cleft types but was more pronounced for cleft lip only and cleft palate only. ConclusionsOur findings suggest that the risk of oral clefts associated with maternal smoking is largest among underweight mothers, although the smoking–BMI interaction is strongest for cleft lip only and cleft palate only. BMI was not protective for the effects of smoking; a clinically relevant increase in smoking-related cleft risk was still present among heavier women.