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Abnormal Respiratory Control Found in Infants Who Later Died of SIDS

Date: Mon, 20 May 1996 13:04:25 -0700

The following may be of interest. It was taken from the NICHD website.
These and similar findings suggest the presence of an underlying
abnormality in cardiorespiratory control. The nature of the probable
abnormality (abnormalities) remains to be determined. It is worth noting
that not all SIDS-related research is funded by NICHD. NHLBI (National
Heart, Lung, and Blood Institute) and other NIH branches also fund
research investigating these important questions.

John L. Carroll, M.D.
The Johns Hopkins Children's Center
Baltimore, MD

Abnormal Respiratory Control Found in Infants Who Later Died of SIDS
November 20, 1995

Some infants who later succumb to sudden infant death syndrome, or SIDS,
exhibit impairment in their ability to control breathing during sleep as
early as the first week of life, according to a new study funded by the
National Institute of Child Health and Human Development (NICHD). These
findings differ from earlier reports of normal overall breathing patterns
in SIDS victims, and indicate that the defect underlying SIDS may occur
before birth, during fetal development.

In this new study, scientists at the University of California at Los
Angeles (UCLA), in collaboration with scientists at the Brompton Hospital
and the University of Sheffield in Great Britain, recorded heart and
breathing patterns in 6,914 apparently normal, healthy infants that ranged
in age from two to 65 days. Sixteen of the infants in this group later
died of SIDS.

Investigators then compared 16 physiologic recordings of SIDS victims to
35 recordings of age-matched control infants. Unlike previous studies that
used gross measures of respiratory rate--and found no differences in
overall respiratory rate or variation--this study used a unique measure,
originally designed to detect changes in heart rate, to plot the amount of
time from one breath to the next, or the breath-to-breath interval.

Using this approach, the investigators were able to compare each
breath-to-breath interval to the previous one while controlling for
breathing rate. They found that infants who later died of SIDS exhibited
less variation in breath-to-breath intervals at slow breathing rates
during sleep than did infants who survived. Specifically, breaths
following long breaths showed less change in infants who later died. This
finding indicates a more "rigid" control of respiration, and,
theoretically, less responsiveness to physiologic input than that found in
control infants.

"If you look at the moment-to-moment changes, what you find is that at
very slow breathing rates, such as those found during sleep, infants that
later die don't change their breathing intervals as much as normal
infants," explained NICHD grantee and project investigator Dr. Ronald
Harper, of UCLA. "The altered breathing patterns suggest a subtle
difference in the control of breathing in infants who die of SIDS. Such a
difference points to the brain areas which fail when vulnerable infants
encounter a potentially lethal respiratory challenge during sleep."
Harper's research team included Drs. V.L. Schechtman and M.Y. Lee of UCLA,
Dr. A. J. Wilson of the University of Sheffield, and Dr. D. Southall,
formerly of the Brompton Hospital and now at Staffordshire Hospital, who
provided the data for the study.

SIDS is defined as the sudden, unexplained death of an infant under one
year of age. Death is associated with a sleep period. Approximately
5,000-6,000 U.S. infants die of SIDS each year, making it the leading
cause of death among infants one month to one year of age. Usually,
infants are apparently healthy before succumbing to SIDS, and show no
signs of danger.

Previous studies by Dr. Harper and colleagues have identified abnormal
heart-rate variability in infants who later died of SIDS. These studies
found an apparent restriction in the extent of change from one heartbeat
to the next in these infants. Because heart and breathing rates are so
deeply intertwined--simply changing from a seated to an upright position
causes a change in breathing rate and a compensatory change in blood
pressure--Dr. Harper and his team of researchers were inspired to
investigate moment-to-moment breathing patterns. "The cardiac patterning
differences indicated that there must be some change in breathing, because
heart rate and breathing are so closely interrelated; you can't really get
a change in one without getting a change in the other, in normal
circumstances," Dr. Harper said.

Another factor implicating respiratory-control problems was that SIDS
infants have fewer breathing pauses, or apnea, than other infants.
Although breathing pauses normally occur in infants, earlier studies done
by these researchers found that infants who later died of SIDS exhibited
fewer short pauses in breathing, even though their respiratory rates and
variability were normal.

The findings from this new study offer the hope of eventually developing
screening tests to identify infants who are at risk. The next step is to
try to identify the brain structures involved and the developmental stage
at which the defect may occur. Dr. Harper and his team are already trying
to do this in animal studies using tiny cameras that record the firing of
nerve cells in response to various physiological changes, such as an
elevation in blood pressure or a change in inspired carbon dioxide.
Another promising, but more expensive, approach involves using the
technique of functional magnetic resonance imaging to visualize the brain
areas that respond to respiratory challenges.

The disturbed breathing signs appear as early as the first week of life,
suggesting that factors responsible for the defect operate before birth.
"If we know where those brain structures are and if we know when in fetal
life those neurons are developing, then we can perhaps target a time
during fetal development that an aberration has occurred," explained Dr.
Harper, who presented the new study last week in San Diego, Ca., at a
press conference held by the Society for Neuroscience.

Other studies, both in this country and abroad, have linked infant prone
(stomach) sleeping with an increased risk of SIDS, and back or side
sleeping with a reduction in risk. Since 1992, when the American Academy
of Pediatrics recommended that infants be placed on their backs or sides
to sleep to reduce the incidence of SIDS, the United States has seen a
steady decrease in the prevalence of infant prone sleeping. This--
more--decrease has been bolstered by the national "Back to Sleep"
campaign, launched last year by a coalition of Federal agencies, including
the NICHD, and by the American Academy of Pediatrics, the SIDS Alliance,
and the Association of SIDS Program Professionals, to disseminate the
message to parents and caretakers that back or side sleeping reduces the
risk of SIDS.

Already, there are signs that the campaign may be working. A national
telephone survey, made last spring, of 1,000 night-time caretakers of
infants seven months and younger indicated that infant sleeping practice
has changed from 70 percent of infants being placed on their stomach
(prone) to sleep, to 70 percent being placed on their back or side, NICHD
Director Dr. Duane Alexander announced on October 17 at a Congressional
briefing on SIDS. "Although it is too soon to tell for sure, there are
encouraging signs that SIDS deaths are declining, especially in states
that have active 'Back to Sleep' promotional campaigns," he said.
"Preliminary SIDS rates this past winter were substantially and
significantly below those of the previous three years." While these are
encouraging signs, Dr. Alexander emphasized that much remains to be done.
The goal is to get more than 90 percent of infants to be placed to sleep
on their back or side.

The NICHD is distributing free "Back to Sleep" publications and other
materials on reducing the risk of SIDS, including a brochure for parents;
a simplified-language brochure in both English and Spanish; a brochure for
health-care professionals; crib stickers; take-home cards to distribute in
hospitals and maternity clinics; posters; videotapes; and public service
announcements (for the media only). To order, write to NICHD/Back to
Sleep, 31 Center Drive, MSC 2425, Room 2A32, Bethesda, MD 20892-2425, or
call toll-free 1-800-505-CRIB.

The NICHD is part of the National Institutes of Health, the biomedical
research arm of the Federal government. Since its inception in 1962, the
NICHD has become a world leader in promoting research on development
before and after birth; maternal, child, and family health; medical
rehabilitation; and reproductive biology, including fertility regulation,
and population issues.

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