Whether sleep environment is safe or not, SIDS is linked to brainstem abnormality

Inborn vulnerabilities can tip infants toward SIDS.

Epidemiologic studies have shown that infants who die suddenly, unexpectedly and without explanation—what’s referred to as sudden infant death syndrome, or SIDS—are often found sleeping face down with their face in the pillow, or sleeping next to an adult. These are environments that have the potential to cause smothering and asphyxiation. By advising parents to have infants sleep on their backs, in a separate crib or bed, the government’s Safe to Sleep campaign (formerly known as Back to Sleep) has greatly reduced deaths from SIDS.

Hannah Kinney, MD, a neuropathologist at Boston Children’s Hospital, is clear that this campaign must go forward—it’s saved thousands of lives. But still, she receives calls from parents and grandparents haunted by their infants’ death, feeling at fault and wanting a second opinion.

And in many cases, she has been able to document abnormalities in brainstem circuits that help control breathing, heart rate, blood pressure and temperature control during sleep.

What’s lacking is early detection and treatment.

For more than 20 years, Kinney’s lab has been one of the few in the world studying the biological underpinnings of SIDS. She believes that in many infants dying suddenly, brainstem circuits that help control breathing, heart rate, blood pressure and temperature control during sleep are abnormal. As a result, when faced with smothering or overheating, these infants fail to rouse, turn their heads or throw off covers as a normal infant would.

The lab’s latest study, reported online this week in the journal Pediatrics, reexamined its data, taking a closer look at the infants’ sleeping environment. Kinney and colleagues reviewed the cases of 71 infants who died suddenly and unexpectedly, were autopsied at the San Diego County Medical Examiner’s office from 1997 to 2008, and had brainstem samples available for analysis. Using death-scene investigation reports, they grouped the infants according to sleep circumstances—those environments considered likely to generate asphyxia and those that weren’t.

In the end, they compared 15 infants with SIDS whose deaths were deemed not to involve asphyxia (group A), 35 SIDS infants whose deaths were possibly asphyxia-related (group B) and nine infants who clearly died from other causes (controls). They excluded the other infants, who either had insufficient data or had evidence of other clear risk factors for death, like exposure to drugs.

And here’s what they found. Infants in both group A and B had abnormalities involving serotonin levels, serotonin receptors, GABA receptors and 14-3-3 (a protein that regulates serotonin). These abnormalities were the same in both groups, even though group A had no environmental risk factors for asphyxia. Both groups had significant biochemical differences from the controls.

“Even the infants dying in a potentially asphyxia-generating situation had an underlying brainstem abnormality that likely made them vulnerable to sudden death if there was any degree of asphyxia,” Kinney explains. “The abnormality prevents the brainstem from responding to the asphyxial challenge and waking.”

What this study adds, therefore, is the realization that not all infants who die in compromised sleep environments are normal: many have underlying vulnerabilities that may tip them toward SIDS.

“Certainly, there are compromised sleeping environments that can cause any baby to die, such as entrapment in the crib,” Kinney says, “but if it’s just sleeping face down, the baby who dies may have an underlying brainstem vulnerability.”

Currently, serotonin deficiency isn’t a recognized disease, and there are no commercial tests or standards. In part this is because of the difficulty of conducting SIDS research, which requires getting tissue from the infants. Kinney has relied upon the San Diego County Medical Examiner’s Office, because it preserves the tissue and because California has a state law that facilitates using it for research purposes.

“Safe sleep practices absolutely remain important, so these infants are not put in a potentially asphyxiating situation that they cannot respond to,” Kinney says. “But we also have to find ways to test for this underlying vulnerability in living babies and then to treat it. Our team is focused now upon developing such a test and treatment.”