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.


METHODS
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 409 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 >or=2 ng/mL.


RESULTS
We observed odds ratios of 2.1 (95% CI, 1.0-4.4) for clefts and 0.4 (95% CI, 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% CI, 1.1-5.3) and 0.6 (95% CI, 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% CI, 0.9-11.9) and 1.7 (95% CI, 0.7-4.2), respectively.


CONCLUSIONS
Smoking exposures, as measured with cotinine levels during mid-pregnancy, were associated with increased risks of clefts and possibly reduced risks of NTDs.
Shaw
Gary M
GM
March of Dimes California Research Division, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA. gshaw@marchofdimes.com
Carmichael
Suzan L
SL
Vollset
Stein Emil
SE
Yang
Wei
W
Finnell
Richard H
RH
Blom
Henk
H
Midttun
Øivind
Ø
Ueland
Per M
PM
D000328:Adult; D002971:Cleft Lip / Q000453:epidemiology*; D002972:Cleft Palate / Q000453:epidemiology*; D003367:Cotinine / Q000097:blood*; D005260:Female; D006801:Humans; D009436:Neural Tube Defects / Q000453:epidemiology*; D016017:Odds Ratio; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D011446:Prospective Studies; D012907:Smoking / Q000453:epidemiology*
D003367:Cotinine