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Oral clefts, smoking & variation of toxin biotransformation

Institution: Children's Hospital Oakland Research Institute
Investigator(s): Edward Lammer, M.D.
Award Cycle: 2004 (Cycle 13) Grant #: 13RT-0109 Award: $623,472
Subject Area: General Biomedical Science
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Smoking during pregnancy increases the risks for a number of health problems for developing babies. Many people are unaware that smoking during pregnancy is a risk factor for two common birth defects of the face, cleft lip and cleft palate - commonly referred to as orofacial clefts. Smoking nearly doubles the risk that a mother will deliver a baby with a cleft. The purposes of this research are to investigate genes that may affect a baby’s susceptibility to orofacial clefts caused by smoking during pregnancy, to investigate how a mother’s genes may influence her smoking behavior, and to investigate whether secondhand smoke breathed by pregnant woman might also increased her risk to have a baby with an orofacial cleft.

The association between maternal smoking and orofacial clefts has been assessed in many studies, and reviews of all of these studies suggests a modest positive association for both cleft lip ±cleft palate and cleft palate alone. An objective of our research was to assess the association between maternal smoking and environmental tobacco smoking and the occurrence of orofacial clefts in an unusually large population-based case-control study of major birth defects in the United States. The consistent case definition and classification and the level of detail available on maternal smoking and environmental tobacco smoke exposure make this study unique in its ability to contribute to our understanding of the association between orofacial clefts and maternal tobacco exposure. The National Birth Defects Prevention Study (NBDPS) is an ongoing, nine-state, case-control study of environmental and genetic risk factors for major birth defects coordinated by the Centers for Disease Control and Prevention (CDC). Eight Centers for Birth Defects Research and Prevention contributed data for this analysis: Arkansas, California, Iowa, Massachusetts, New Jersey, New York, Texas, and CDC (Atlanta, GA).

Among the 3,390 control mothers, 20% smoked during the month before conception and two months following conception, compared to 24% for mothers of infants with cleft lip ±cleft palate and 23% for mothers of infants with cleft palate alone. Periconceptional maternal smoking was associated with an approximate 30% increase in the occurrence of orofacial clefts, and in particular of cleft lip ±cleft palate. The effect was strongest for bilateral cleft lip and for isolated cleft lip ±cleft palate. Among the heaviest smokers, bilateral cleft lip ±cleft palate was nearly 5 times more likely to occur than among nonsmoking mothers. Overall, the heaviest smokers were about twice as likely to have an infant with an orofacial cleft than nonsmokers. Environmental tobacco exposure was associated with cleft palate alone-infants who had associated major malformations and with females who had isolated cleft palate alone; but overall, the contributions of environmental tobacco smoke exposure to cleft risks appeared to be to quantitatively add to the “dose” among mothers who smoked, rather than creating a significant increased risk for clefts among mothers who were not smokers. This was one of the largest population-based, case-control studies to investigate the association between smoking during pregnancy and risk for orofacial clefts. The detailed case review for this project allowed us to analyze a number of specific case subgroups with clefts, while our detailed information on the number of cigarettes smoked and environmental tobacco exposure for each of the pregnancy months allowed us to look at dose-response effect of total smoke exposure, and to define our unexposed group very carefully as women who were not exposed to tobacco during pregnancy. These important results add to the studies showing that smoking during pregnancy nearly doubles the risk to have an infant with an orofacial cleft, and that environmental tobacco exposures contribute, in a small additive manner, to the risks among mothers who already smoke while pregnant
Publications

Effect of maternal smoking and enviromental tobacco smoke exposure on the occurrence of orofacial clefts
Periodical: Epidemiology Index Medicus:
Authors: Edward J Lammer, MD ABS
Yr: 2007 Vol: 18 Nbr: 2 Abs: Pg: 226-233

Maternal smoking during early pregnancy
Periodical: Cleft Palate-Craniofacial Journal Index Medicus:
Authors: Edward J. Lammer, MD ART
Yr: 2007 Vol: 44 Nbr: 4 Abs: Pg: 366-73

Maternal stress life events and risks of birth defects
Periodical: Epidemiology Index Medicus:
Authors: Edward J. Lammer , MD ART
Yr: 2007 Vol: 18 Nbr: 3 Abs: Pg: 356-361

Maternal Smoking and Enironmental Tobacco Smoke Exposure and the Risk of Orofacial Clefts
Periodical: Epidemiology Index Medicus:
Authors: Margaret A. ART
Yr: 2007 Vol: Nbr: Abs: Pg:

Endolthelial Nitric Oxide Synthase( NOS3) Genetic Variants, Maternal Smoking, Vitamin Use and Risk of Human Orofacial Clefts.
Periodical: American Journal of Epidemiology Index Medicus:
Authors: Gary M. Shaw, David M Iovannisci, Wei Yang, Richard H. Finnell, Suzan L. Carmichael ART
Yr: 2005 Vol: 132 Nbr: 12 Abs: Pg:

Maternal Stressful Life Events and Risk of Birth Defects.
Periodical: Epidemiology Index Medicus:
Authors: Suzan L. Carmichael, Gary M. Shaw, Wei Yang, Barbara Abrams ART
Yr: 2007 Vol: 18 Nbr: 3 Abs: Pg: 365-361