Maternal Periconceptional Exposure to Cigarette Smoking and Congenital Limb Deficiencies

Background Congenital limb deficiencies ( LD )s are characterised by the failure or disruption in formation of limbs or digits. Epidemiological research on maternal exposure to cigarette smoke and LDs is inconclusive. Methods Data from the N ational B irth D efects P revention S tudy were used to examine LDs and maternal exposure to active or passive cigarette smoke. Mothers of LD case ( n  = 906) and unaffected control ( n  = 8352) pregnancies from O ctober 1997 through D ecember 2007 reported on exposure type and quantity. Logistic regression was used to estimate adjusted odds ratio ( OR ) and 95% confidence interval [95% CI ]; interactions with folic acid ( FA ) intake were tested. Results For any LD , OR s were elevated for active (1.24 [95% CI 1.01, 1.53]), passive (home) (1.28 [95% CI 1.03, 1.59]), and ‘active and passive’ (1.34 [95% CI 1.05, 1.70]) exposures. The OR s for longitudinal LDs were elevated for passive (home) (1.62 [95% CI 1.14, 2.31]) and ‘active and passive’ (1.62 [95% CI 1.09, 2.41]) exposures. The OR for pre‐axial LDs were elevated for any (1.39 [95% CI 1.01, 1.90]), active (1.53 [95% CI 1.03, 2.29]), passive (home) (1.82 [95% CI 1.23, 2.69]), and ‘active and passive’ (1.87 [95% CI 1.20, 2.92]) exposures. For lower limbs, ORs were elevated for passive (home) (1.44 [95% CI 1.01, 2.04]) and smoking 15 or more cigarettes/day (2.25 [95% CI 1.27, 3.97]). Interactions showed that ORs for any passive smoke exposure were 0.43 and 0.59 higher in the absence of FA intake for any and terminal transverse LDs . Conclusions Maternal active smoking and exposure to passive cigarette smoke emerged as a potential teratogen that affects limb and digit formation. FA was not found to mitigate the impact.