|SIDS Infants Show Abnormalities In Brain Area
Controlling Breathing, Heart Rate
Serotonin-Using Brain Cells Implicated In Abnormalities
Infants who die of sudden infant death syndrome have abnormalities
in the brainstem, a part of the brain that helps control heart
rate, breathing, blood pressure, temperature and arousal, report
researchers funded by the National Institutes of Health. The finding
is the strongest evidence to date suggesting that innate differences
in a specific part of the brain may place some infants at increased
risk for SIDS.
The abnormalities appeared to affect the brainstem’s ability to
use and recycle serotonin, a brain chemical which also is used
in a number of other brain areas and plays a role in communications
between brain cells. Serotonin is most well known for its role
in regulating mood, but it also plays a role in regulating vital
functions like breathing and blood pressure.
The study appears in the November 1 Journal of the American
Medical Association and was conducted by researchers in
the laboratory of Hannah Kinney, M.D., at Children’s Hospital
Boston and Harvard Medical School as well as other institutions.
“This finding lends credence to the view that SIDS risk may greatly
increase when an underlying predisposition combines with an environmental
risk — such as sleeping face down — at a developmentally
sensitive time in early life,” said Duane Alexander, M.D., Director
of the NIH’s National Institute of Child Health and Human Development.
SIDS is the sudden and unexpected death of an infant under 1 year
of age, which cannot be explained after a complete autopsy, an
investigation of the scene and circumstances of the death, and
a review of the medical history of the infant and his or her family.
Typically, the infant is found dead after having been put to sleep
and shows no signs of having suffered.
In previous studies, researchers have hypothesized that abnormalities
in the brainstem may make an infant susceptible to situations in
which they re-breathe their own exhaled breath, depriving them
of oxygen. This hypothesis holds that certain infants may not be
able to detect high carbon dioxide or low oxygen levels during
sleep, and do not wake up.
To conduct the current study, researchers examined tissue from
the brainstems of 31 infants who died of SIDS and 10 infants who
died of other causes. The tissue was provided by the office of
the chief medical examiner in San Diego, California, and was collected
from infants who died between 1997 and 2005.
The lower brainstem helps control such basic functions as breathing,
heart rate, blood pressure, body temperature, and arousal. The
researchers found that brainstems from SIDS infants contained more
neurons (brain or nerve cells) that manufacture and use serotonin
than did the brainstems of the control infants, explained the study’s
first author, David Paterson, PhD, a researcher at Children’s Hospital
Serotonin belongs to a class of molecules known as neurotransmitters,
which serve to relay messages between neurons. Neurons release
neurotransmitters, which fit into special sites, or receptors,
on surrounding neurons, somewhat like a key fits into a lock. Once
in place, the neurotransmitter either promotes or hinders electrical
activity in the receiving neuron — next in line in a particular
brain circuit — causing it to release its neurotransmitters,
which either excite or inhibit still more neurons, and so on.
Although the brainstem tissue from the SIDS infants contained
more serotonin-using neurons, these serotonin-using neurons appeared
to contain fewer receptors for serotonin than did the brainstems
of control infants. Dr. Paterson noted that there are at least
14 different subtypes of serotonin receptor. In their study, the
researchers tested the infants’ brainstem tissue for a serotonin
receptor known as “subtype 1A.”
Tissue from both the SIDS infants and the control infants contained
roughly equal amounts of a key brain protein, serotonin transporter
protein. This protein recycles serotonin, collecting the neurotransmitter
from the surrounding spaces outside the neuron and transporting
it back into the neuron so it can be used again. Dr. Paterson explained,
however, that because the SIDS infants had proportionately more
serotonin-using neurons than did the control infants, they would
also be expected to have more serotonin transporter protein. So
even though they had equal amounts of serotonin transporter protein,
the levels were nevertheless reduced — relative to the increased
number of serotonin-using neurons — and, for this reason,
unlikely to meet the needs of these cells.
Dr. Paterson added that from the observations in this study it
was not possible to determine how much serotonin the infants’ brainstems
contained when the infants were alive. He noted, however, that
the pattern of abnormalities — more serotonin neurons, an
apparent reduction of serotonin 1A receptors, and insufficient
serotonin transporter — suggested that the level of serotonin
in the brainstems of SIDS infants was abnormal.
“Our hypothesis right now is that we’re seeing a compensation
mechanism,” Dr. Paterson said. “If you have more serotonin neurons,
it may be because you have less serotonin and more neurons are
recruited to produce and use serotonin to correct this deficiency.”
The researchers also found that male SIDS infants had fewer serotonin
receptors than did either female SIDS infants or control infants.
The finding may provide insight into why SIDS affects roughly twice
as many males as females.
“These findings provide evidence that SIDS is not a mystery but
a disorder that we can investigate with scientific methods, and
some day, may be able to identify and treat,” said Dr. Hannah Kinney,
the senior author of the paper.
A large body of research has shown that placing an infant to sleep
on his or her stomach greatly increases the risk of SIDS. The NICHD-sponsored
Back to Sleep campaign urges parents and caregivers to place infants
to sleep on their backs, to reduce SIDS risk. The campaign has
reduced the number of SIDS deaths by about half since it began
in 1994. The campaign also cautions against other practices that
increase the risk of SIDS, such as soft bedding, smoking during
pregnancy, and smoking around a baby after birth.
Despite the fact that the Back to Sleep Campaign recommendations
had been widely distributed by the time the study began, a large
proportion of the SIDS cases in the study by Drs. Paterson, Kinney
and their coworkers were correlated with known SIDS risk factors:
15 (48 percent) were found sleeping on their stomachs, 9 (29 percent)
were found face down, and 7 (23 percent) were sharing a bed, at
the time of death.
“The majority (65 percent) of the SIDS cases in this data set,
however, were sleeping prone or on their side at the time of death,
indicating the need for continued public health messages on safe
sleeping practices, the study authors wrote.”
Information and free materials on ways parents and caregivers
can reduce the risk of sudden infant death syndrome are available
on the Back to Sleep Campaign Web site at http://www.nichd.nih.gov.
Additional information about the search for ways to identify infants
most at risk for SIDS in the accompanying backgrounder, “Searching
For Those At Greatest Risk For SIDS,” at http://www.nichd.nih.gov/news/releases/sids_serotonin_backgrounder.cfm.
The NICHD sponsors research on development, before and after
birth; maternal, child, and family health; reproductive biology
and population issues; and medical rehabilitation. For more information,
visit the Institute’s Web site at http://www.nichd.nih.gov/.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.