Exposure to cigarette smoke in the womb may dampen a baby’s fight-or-flight responses, leaving the newborn vulnerable to sudden infant death syndrome, a study in rats suggests. It has been known that babies exposed to the smoke have a higher risk of the syndrome, in which seemingly healthy infants inexplicably die. The new study, appearing June 3 in The Journal of Neuroscience, may explain why, the researchers report.

“SIDS is a complicated disease, and this is why you need these kinds of studies,” comments Ernest Cutz, a pediatric pathologist at The Hospital for Sick Children in Toronto.

Researchers led by Colin Nurse, a neurobiologist at McMaster University in Hamilton, Canada, studied chromaffin cells, which are located in the adrenal gland of both rats and humans. In alarming situations — like when a baby is, for any number of reasons, not getting enough oxygen — these cells flood the body with chemical signals called catecholamines. These signals, which include adrenaline, stimulate the fight-or-flight response. “Catecholamines are very important alarm mechanisms that wake a baby up,” Nurse says.

The chromaffin cells of newborn rats that were exposed to nicotine while in their mothers’ womb produced more of a protein that dampens the cells’ responses. This protein, called a potassium ATP channel, normally acts as a brake by preventing the cells from releasing the fight-or-flight signals in nonthreatening situations, Nurse says. For the rats that have been exposed to nicotine, he says, “the brake has become too strong.” Fetal nicotine exposure prevented the cells from later sounding the alarm and releasing catecholamines when the researchers deprived the rats of oxygen, Nurse and his colleagues found.

Not only did rats exposed to nicotine in the womb have abnormally high levels of potassium ATP channels, these rats were more likely to die in low-oxygen conditions than were young rats not exposed to nicotine in the womb.

Nurse says the process probably explains why fetuses exposed to cigarette smoke during development end up having a higher risk of SIDS. “With smoking mothers, the nicotine is getting to the fetus at a time the nervous system is developing,” Nurse says. “If systems are perturbed, you can’t respond appropriately.”

The higher death rate among the rats was reversed when the fetuses were treated with a drug called glibenclamide before nicotine exposure. Glibenclamide, commonly used to treat diabetes in adults, acts on the same potassium ATP channels that nicotine affects. “We were able to reverse the adverse effects of nicotine,” Nurse says.

“The paper adds to the knowledge in the field,” says Rosemary Horne of the Monash Institute of Medical Research in Clayton, Australia. But she cautions that it’s too early to say whether glibenclamide could reduce the risk of SIDS in people.

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