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BACKGROUND: Clubfoot is a common birth defect that affects one or both feet. Evidence suggests increased risks of clubfoot in offspring associated with maternal medication and cigarette smoking exposure in early pregnancy. We explored whether such associations differed by clubfoot laterality. METHODS: This case-control study was conducted in Massachusetts, North Carolina, and New York (2007-2011). State birth defects registries reported clubfoot diagnoses among infants aged 10 cigarettes per day for bilateral clubfoot (OR 2.42, 95% CI 1.37, 4.28). Acetaminophen, antihistamines, and pseudoephedrine were not associated with increased risk across laterality groups (ORs ranged 0.42 to 1.05). Elevated ORs (1.22 to 1.44) were observed for ibuprofen use for each laterality group. Associations for salicylates and ondansetron use, however, were observed for bilateral cases only (OR 1.82, 95% CI 1.07, 3.09; OR 1.64, 95% CI 0.99, 2.73, respectively). CONCLUSIONS: The pattern of associations across laterality varied by risk factor, suggesting a complex pathogenesis of clubfoot laterality. Investigations that can incorporate both genetic and environmental risk factors are needed to understand clubfoot etiologies.
Casey et al. (Mon,) studied this question.