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Differential Effects of Maternal Exposures on Clubfoot Laterality: A Case-Control Study
Sharon M Casey1, Molly N Hoffman1, Martha M Werler1
1Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA.
Insights
Maternal smoking during pregnancy increases clubfoot risk, particularly for bilateral cases. Risk factors for clubfoot vary by laterality, indicating complex causes.
Area of Science:
- Pediatric Orthopedics
- Birth Defect Research
- Environmental Epidemiology
Background:
- Clubfoot is a common congenital birth defect affecting foot development.
- Maternal exposure to cigarette smoking and certain medications in early pregnancy is linked to increased clubfoot risk.
- Understanding how these exposures influence clubfoot laterality is crucial for prevention.
Purpose of the Study:
- To investigate the association between maternal exposures and clubfoot risk, considering laterality (bilateral, left, or right).
- To determine if specific risk factors have different impacts based on whether clubfoot affects one or both feet.
Main Methods:
- A case-control study was conducted across three US states from 2007-2011.
- Infants with clubfoot (cases) and infants without birth defects (controls) were identified through state registries.
- Mothers were interviewed about exposures, and logistic regression analyzed odds ratios (OR) and confidence intervals (CI).
Main Results:
- Maternal smoking, especially over 10 cigarettes daily, showed the highest association with bilateral clubfoot (OR 2.42).
- Ibuprofen use was linked to increased risk across all laterality groups (ORs 1.22-1.44).
- Salicylates and ondansetron were associated with bilateral clubfoot risk, but not unilateral cases.
Conclusions:
- The relationship between maternal exposures and clubfoot risk differs based on laterality.
- Clubfoot's complex etiology likely involves both genetic and environmental factors, varying by foot presentation.
- Further research incorporating genetic and environmental interactions is needed to fully understand clubfoot development.
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.