Discoveries and Data: Exposures and Risk Factors


In the US, about 1 in 8 women smokes during pregnancy. Both carbon monoxide and nicotine—agents released through smoking—may lower the oxygen available to the fetus. Other components of cigarettes have been linked to birth defects in laboratory animals as well. Although the health effects of smoking during pregnancy are well documented, until recently, evidence about smoking’s impact on birth defects was not clearcut.


Past studies hinted that smokers’ babies may be more likely to have cleft lip and/or cleft palate, but results were mixed. Are some infants genetically more susceptible to mothers’ smoking? The Program looked at a gene normally involved in development of the palate and mouth—the transforming growth factor-alpha gene (TGFalpha-9211452).

bullet-1824005 Women who smoke during pregnancy were 1.5 to 2 times as likely to have babies with oral clefts. The more cigarettes the mother smoked, the higher the risk.
bullet-1824005 The hazards of smoking are even greater for the 1 in 7 babies who carry a cleft-susceptibility gene (the A2 form of TGFalpha-9211452). They were 8 times as likely to have oral clefts if their mothers smoked. Those born to nonsmoking mothers were at no greater risk.
bullet-1824005 Nonsmoking mothers exposed to secondhand smoke had only a small, if any, increased risk. Father’s smoking increased the risk for oral clefts only if the mother smoked too.
bullet-1824005 Cutting out smoking could prevent more than 200 oral clefts in California each year.



bullet-1824005 Heart and limb defects. In other birth defects studied, the connection with smoking is not straightforward. For example, we saw a modest risk increase for conotruncal heart defects and limb defects, but only if both parents smoked. Perhaps smoking patterns are different (for instance, more cigarettes/day) when both parents smoked, or the risk increase could be due to other behaviors more common among smokers. ref_book-9017305
bullet-1824005 Neural tube defects. Parents’ smoking did not increase risk. ref_book-9017305
bullet-1824005 Down syndrome. Environmental factors—interacting with the developmental instability caused by an extra chromosome—may influence which babies have associated abnormalities. Babies with Down syndrome whose mothers smoked during the first trimester had double the risk for heart defects. ref_book-9017305