Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls

results: Significant positive associations with maternal smoking were found for: cardiovascular/heart defects (OR 1.09, 95% confi- dence interval (CI) 1.02 -1.17); musculoskeletal defects (OR 1.16, 95% CI 1.05- 1.27); limb reduction defects (OR 1.26, 95% CI 1.15 -1.39); missing/extra digits (OR 1.18, 95% CI 0.99 -1.41); clubfoot (OR 1.28, 95% CI 1.10 -1.47); craniosynostosis (OR 1.33, 95% CI 1.03 -1.73); facial defects (OR 1.19, 95% CI 1.06 -1.35); eye defects (OR 1.25, 95% CI 1.11 -1.40); orofacial clefts (OR 1.28, 95% CI 1.20 -1.36); gastrointestinal defects (OR 1.27, 95% CI 1.18 -1.36); gastroschisis (OR 1.50, 95% CI 1.28 -1.76); anal atresia (OR 1.20, 95% CI 1.06 -1.36); hernia (OR 1.40, 95% CI 1.23 -1.59); and undescended testes (OR 1.13, 95% CI 1.02 -1.25). There was a reduced risk for hypospadias (OR 0.90, 95% CI 0.85- 0.95) and skin defects (OR 0.82, 0.75- 0.89). For all defects combined