Mid-Pregnancy Cotinine and Risks of Orofacial Clefts and Neural Tube Defects

Objective Past studies of cigarette smoking as a contributor to orofacial clefts and neural tube defects (NTDs) used self-reports of smoke exposures. We have correlated measurements of cotinine (a nicotine metabolite) in mid-pregnancy sera with clefts and NTDs. Study design From a repository of > 180 000 mid-pregnancy serum specimens collected in California from 2003 to 2005 and linked to delivery, outcome information, we identified 89 orofacial cleft-associated pregnancies, 80 NTD-affected pregnancies. and randomly selected 469 pregnancy specimens that corresponded to infants without malformations as control subjects. Cotinine was measured by liquid chromatography-mass spectrometry. No smoke exposure was defined as cotinine values <2 ng/mL. and any exposure was defined as >= 2 ng/mL. Results We observed odds ratios of 2.1 (95% Cl, 1.0-4.4) for clefts and 0.4 (95% Cl, 0.1-1.7) for NTDs associated with exposure. After adjusting for race/ethnicity, age, and serum folate levels, odds ratios were 2.4 (95% Cl. 1.1-5.3) and 0.6 (95% Cl, 0.1-2.5). We explored 2 cotinine levels, 2 to 10 ng/mL and >10 ng/mL for clefts (data were too sparse for NTDs). Odds ratios for these levels were 3.3 (95% Cl. 0.9-11.9) and 1.7 (95% Cl, 0.7-4.2). respectively. Conclusion Smoking exposures, as measured with cotinine levels during mid-pregnancy. were associated with increased risks of clefts and possibly. reduced risks of NTDs., (J Pediatr 2009:154:17-9)