|Cold Treatment Protects Against Infant Disability and Death
From Oxygen Loss
Lowering infants’ body temperature to about 92 degrees Fahrenheit within the
first 6 hours of life reduces the chances of disability and death among full
term infants who failed to receive enough oxygen or blood to the brain during
birth. This finding was reported by researchers in the Neonatal Research Network
of the National Institute of Child Health and Human Development, one of the National
Institutes of Health.
The study appears in the October 13, 2005 New England Journal of Medicine.
“The experimental cooling of newborns to prevent death and injury from oxygen
deprivation during birth is extremely promising,” said NICHD Director Duane Alexander,
M.D. “Yet it would be premature to implement the study results under any but
the most carefully controlled and monitored circumstances. The potential for
serious harm exists if the conditions followed in this protocol are not carried
out precisely as they were during the study, by personnel skilled in their use.”
The study was led by Seetha Shankaran, M.D., of the Division of Neonatal-Perinatal
Medicine, at Wayne State University School of Medicine in Detroit, one of the
participating NICHD Neonatal Research Network study sites.
Hypoxic ischemic encephalopathy (HIE) occurs when an infant’s brain fails to
receive sufficient oxygen or sufficient blood before birth. HIE may occur hours
before birth, or, in some cases, during labor and delivery. The condition may
result from a variety of causes. These include compression of the placenta, tearing
of the placenta from the uterine wall before birth, compression of the umbilical
cord, and rupture of the uterus. Dr. Shankaran explained that HIE is estimated
to occur from 0.5 to 1 times per every thousand births.
The study authors wrote that 10 percent of infants with moderate HIE die, as
do 60 percent of infants with severe HIE. “Many, if not all,” survivors of severe
HIE experience major disability, they added.
Previous studies, conducted in laboratory animals, suggested that cooling the
brain from 2 to 5 degrees Celsius after HIE could reduce the chances for the
death and disability that often result from HIE, the authors wrote.
To conduct the study, researchers enrolled infants from the 15 centers making
up the NICHD neonatal network. All the infants had experienced oxygen deprivation
during the birth process. A total of 208 infants took part in the study. They
were assigned at random to 1 of 2 groups, with 102 infants undergoing the experimental
cooling (hypothermia) treatment and 106 receiving standard care. Standard care
for HIE may involve placing the infant on a ventilator to assist breathing monitoring
blood pressure, and providing fluids intravenously, and other newborn intensive
care supportive therapies.
The infants were cooled by placing them on a soft plastic blanket through which
water circulates. The blanket’s temperature is regulated by computer. For the
study, the blankets were set at 5 degrees Celsius (41 degrees Fahrenheit). The
infant’s temperatures were lowered to 33.5 degrees Celsius (92.3 degrees Fahrenheit),
as measured by a temperature probe placed in an infant’s esophagus. The infants
in the hypothermia group were enrolled within the first 6 hours of birth, and
remained on the cooled blanket for 72 hours. After 72 hours had passed, they
were gradually warmed to a normal body temperature.
Infants in both the hypothermia group and the control group received standard
newborn intensive care including monitoring of vital signs and were watched carefully
for signs of organ dysfunction.
When the infants were examined at 18 to 22 months of age, 44 percent of those
in the hypothermia group developed a moderate to severe disability or had died,
as compared to 62 percent in the control group.
Dr. Shankaran explained that when the study’s three principal outcomes — death,
moderate disability, and severe disability — were considered as one unit, the
difference between the two groups of infants was statistically significant. However,
when these three adverse outcomes were analyzed as separate categories, the difference
between the two groups of infants for any individual outcome was not statistically
Dr. Shankaran explained that it was not possible to recruit enough infants to
arrive at statistically significant measures for the differences in the various
outcomes between the two groups. Because HIE occurs infrequently, it took 3 years
to enroll enough infants to conduct the current study from the 15 participating
NICHD Neonatal Research Network sites.
In terms of the actual number of infants affected, fewer infants in the hypothermia
group died or experienced moderate or severe disability than was experienced
by infants in the control group. For example, 24 infants in the hypothermia group
died, as compared to 38 in the control group. Similarly, 15 infants in the hypothermia
group experienced disabling cerebral palsy, compared to 19 infants in the control
group. Blindness occurred in 5 infants in the hypothermia group and in 9 infants
in the control group. Infants in the hypothermia group also averaged higher on
measures of infant mental and physical development than did infants in the control
“A concern with any therapy that reduces mortality among infants at high risk
of death and disability is the possibility of an increase in the number of infants
who survive with disabilities,” the study authors wrote. “In our study there
was no evidence of increased rates of moderate or severe disability at 18 to
22 months of age among infants treated with hypothermia.”
Side effects of the treatment consisted of a temporary hardening and drying
of the skin where the skin came in contact with the cooling blanket, Dr. Shankaran
“Physicians need to exercise extreme caution in putting the study’s results
into practice,” said Rose Higgins, M.D., program scientist for the NICHD Neonatal
Research Network and an author of the study. “Most newborn intensive care units
don’t have the resources or experienced personnel to duplicate the carefully
controlled conditions of the study.”
Dr. Higgins added that comparatively minor fluctuations in an infant’s body
temperature-perhaps by as little as a few degrees-could result in serious harm
if not closely monitored by trained personnel.
During the 72 hours of the hypothermia treatment, personnel trained in life
support and use of the cooling blanket monitored all infants continuously. Fluctuations
in the infant’s temperature were compensated for immediately by adjustments to
the cooling blanket.
Moreover, only full-term infants took part in the study, Dr. Higgins said. It
is not known whether preterm infants with HIE would benefit or be harmed from
Dr. Higgins said that the NICHD is currently advising the American Academy of
Pediatrics to develop practice recommendations for treating infants with HIE.
Moreover, three ongoing studies of hypothermia treatment are expected to provide
additional information on the most effective ways to carry out the treatment.
Dr. Higgins added that the NICHD Neonatal Research Network will also follow
both groups of children until they reach the ages of 6 or 7, to compare the incidence
of health problems or learning difficulties.
The NICHD is part of the National Institutes of Health (NIH), the biomedical
research arm of the federal government. NIH is an agency of the U.S. Department
of Health and Human Services. The NICHD sponsors research on development, before
and after birth; maternal, child, and family health; reproductive biology and
population issues; and medical rehabilitation.
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 http://www.nih.gov.