Background: Smoking during pregnancy has been associated with orofacial clefts in numerous studies. However, most previous studies have not been able to assess the relation between maternal smoking and specific phenotypes (eg, bilateral clefts).
Methods: We examined the association between periconceptional maternal smoking, environmental tobacco smoke (ETS) exposure, and cleft lip with or without cleft palate (CLP) (n = 933) and cleft palate only (CPO) (n = 528) compared with infants with no major birth defects (n = 3390). Infants were born between 1 October 1997 and 31 December 2001, and exposures were ascertained from maternal telephone interviews for the National Birth Defects Prevention Study. We excluded infants who had a first-degree relative with an orofacial cleft. Effect estimates were adjusted for folic acid use, study site, prepregnancy obesity, alcohol use, gravidity, and maternal age, education, and race/ethnicity.
Results: Periconceptional smoking was associated with CLP (odds ratio = 1.3; 95% confidence interval = 1.0–1.6), and more strongly associated with bilateral CLP (1.7; 1.2–2.6), with a weaker association observed for CPO. Heavy maternal smoking (25+ cigarettes/day) was associated with CLP (1.8; 1.0–3.2), bilateral CLP (4.2; 1.7–10.3), and CPO with Pierre Robin sequence (2.5; 0.9–7.0). ETS exposure was not associated with CLP or CPO.
Conclusions: This study confirmed the modest association between smoking and orofacial clefts that has been consistently reported, and identified specific phenotypes most strongly affected.