Differential Effects of Maternal Exposures on Clubfoot Laterality: A Case-Control Study

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.