Birth defects research · 2026
Differential Effects of Maternal Exposures on Clubfoot Laterality: A Case-Control Study.
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Casey Sharon M, Hoffman Molly N, Werler Martha M, Parker Samantha E
Аннотация
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 < 11 months. Controls without birth defects were random samples of infants from the same catchment areas and born in the same year as cases. Mothers were interviewed within 12 months following delivery. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI).
RESULTS: Our analysis included 643 isolated cases (bilateral N = 321, left N = 180, right N = 142) and 2037 controls. Estimates for cigarette smoking in early pregnancy were elevated for bilateral, left-sided, and right-sided cases, with the greatest effect for > 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.
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 < 11 months. Controls without birth defects were random samples of infants from the same catchment areas and born in the same year as cases. Mothers were interviewed within 12 months following delivery. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI).
RESULTS: Our analysis included 643 isolated cases (bilateral N = 321, left N = 180, right N = 142) and 2037 controls. Estimates for cigarette smoking in early pregnancy were elevated for bilateral, left-sided, and right-sided cases, with the greatest effect for > 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.