SMOKING RAISES RISK FOR ORAL CLEFTS

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? We looked at a gene normally involved in development of the palate and mouth—the transforming growth factor—alpha gene (TGFa).

	Women who smoke during pregnancy are 1.5 to 2 times as likely to have babies with oral clefts. The more cigarettes the mother smokes, the higher the risk.
	The hazards of smoking are even greater for the 1 in 7 babies who carry a cleft-susceptiblity gene (the A2 form of TGFa). They were 8 times as likely to have oral clefts if their mothers smoked. Those born to nonsmoking mothers were at no greater risk.

DELVING DEEPER INTO FOLIC ACID METABOLISM

Taking vitamins does not eliminate the risk for neural tube defects—why do some pregnancies benefit while others do not? The search to understand how supplements alter risk has focused on a number of genes that influence the developing baby's folic acid metabolism. Variant forms of these genes can lower folic acid levels, particularly if the mother does not take multivitamins containing folic acid. Among babies who inherited variant genes and whose mothers did not use multivitamins, we found:

	MTHFR: About 1 in 6 babies has the genetic type "TT" of methylenetetrahydrofolate reductase (MTHFR); this variant is more common in Latino infants. Babies with type "TT" had a modest increase in spina bifida risk.
	Methionine synthase: The 15% of babies who carry an altered form of this gene did not have a higher risk for spina bifida.
	FR-: We found no variation in the folate receptor alpha (FR-a) gene, responsible for folic acid transport into cells.
	BHMT: Babies who have variants of the BHMT/BHMT2 gene do not have a higher risk for oral clefts.