Family history, maternal smoking, and clubfoot: An indication of a gene-environment interaction

Although epidemiologic studies of some birth defects have suggested a gene- smoking interaction, the possibility of this interaction in clubfoot has no t been examined. The authors analyzed risk factors among 346 infants with i solated clubfoot and 3,029 infants without defects from the Atlanta Birth D efects Case-Control Study. All infants were born during 1968-1980, and moth ers were interviewed in 1982-1983. The authors examined the family history- smoking interaction as an indication of a gene-environment interaction. The y defined "smoking" as smoking any time during the first 3 months of pregna ncy and "family history" as having a first-degree relative with clubfoot. C onditional logistic regression (matching variables: race, birth hospital, a nd birth period) was used to obtain effect estimates. The adjusted odds rat ios were 1.34 (95% confidence interval (CI): 1.04, 1.72) for smoking only, 6.52 (95% CI: 2.95, 14.41) for family history only, and 20.30 (95% CI: 7.90 , 52.17) for a joint exposure of smoking and family history. The effect est imate for the joint exposure was higher than would be expected under either an additive or a multiplicative model of interaction and showed a statisti cally significant departure from additivity. This study confirms the import ance of familiar factors and smoking in the etiology of clubfoot and identi fies a potentially important interaction.