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Anne Hansen, MD, MPH, and Janet Soul, MD, CM |
For years, Children's Hospital Boston has provided life-saving intensive care to infants with hypoxic-ischemic encephalopathy (HIE), or loss of oxygen at birth. But since July of last year, Anne Hansen, MD, MPH, medical director of the NICU, and Janet Soul, MD, CM, associate director of the Neonatal Neurology Program, have been offering newborn patients a new hypothermia treatment that may
prevent or minimize the long-term consequences of brain injury due to HIE: cerebral palsy, cognitive
and visual impairments. Children's is the first and only hospital in Massachusetts to offer this protocol
as therapy.
Perinatal hypoxic-ischemic brain injury is now understood to occur in two phases. The first occurs during the peripartum period when the fetus's brain is exposed to asphyxiation because of inadequate blood flow supplying oxygen to the brain. The
second occurs in the hours after birth and is due to secondary energy failure.
Induced hypothermia aims to minimize the damage or prevent infants from experiencing this second phase of brain injury. It involves placing an infant onto a cooling blanket, which quickly reduces body temperature to approximately 92.3 degrees Fahrenheit. The cooling must be initiated within six hours of birth-preferably as soon as possible. The infant is cooled for 72 hours and then gradually warmed. The babies are monitored with amplitude-integrated electroencephalogram (aEEG), serial
neurological examinations, and laboratory and imaging studies before, during and after the procedure.
There are probably multiple mechanisms by which
hypothermia minimizes brain injury. The lack of oxygen and
glucose to the brain during asphyxia means that energy in the brain cells is depleted, but when the brain and body are cooled, less energy is needed for brain function, which minimizes brain injury. In addition, researchers have shown in animal models that hypothermia works to slow down or halt multiple enzyme
pathways in the brain that lead to death of the brain cells.
Children's has treated three newborns under the new
protocol, with positive outcomes. Prior to therapy, all three infants were found to have abnormal neurological examinations and aEEG readings, indicating that their brains were affected by asphyxia. After completing the treatment, two babies had normal brain MRIs and the third showed only a tiny area of likely inconsequential brain injury. Dr. Soul has seen all three infants during follow-up visits; she says all three are doing "beautifully" and have normal neurological exams. Because this treatment is not being offered as a randomized, controlled trial, the team
cannot definitively conclude that the therapy improved
neurologic outcomes; however, the results are encouraging.
"To have the first patient come in with every risk factor
pointing toward a poor neurologic outcome, and have him whistle out of here with a normal MRI and neurological exam, no seizures and eating well, made us all feel great," says Dr. Hansen. Each infant tolerated the treatment well, without experiencing serious side effects. The infants showed some expected hypothermia-related symptoms, such as slowed heart rate and cold skin.
While the AAP has approved the use of induced hypothermia as treatment for HIE, some in the medical field have argued that clinical trial results have been equivocal and that more research should be completed before implementation. "We feel that if we choose patients carefully and are conservative with who we treat, not deluding ourselves that we can help every baby, we may at least be able to help some babies with perinatal asphyxia," says Dr. Soul.
"The problem is that, other than therapeutic hypothermia, there are currently no other treatment options," says Dr. Hansen. "Until now, we have only had supportive care to offer
ventilators, pressors or anti-epileptics-but nothing to stop or slow down the brain injury. That's the reason why we feel
compelled to offer hypothermia. Studies show it is not harmful and might be helpful."
Infants who receive therapy will be followed by Dr. Soul's team, which will track their cognitive and motor development for at least two years. In the future, the doctors would like to see the service offered at other hospitals, with the full three days of
treatment being offered eventually at other level III NICUs. They hope that the initial aEEG and cooling could be started at level II special care nurseries in the community, prior to transfer to Children's or another NICU offering hypothermia.
"If each of our referral hospitals had a blanket and monitor, they could call us, get an aEEG running while we're preparing to transport and get the baby cooled before the six-hour window closes," says Dr. Hansen. "People need to realize that this is an emergency we're treating. If you have a baby that's asphyxiated, don't wait. The sooner we cool the baby the greater the chance of preventing brain injury."
To consider transfer of a term or late pre-term newborn with
perinatal depression and no other major medical conditions, contact Children's NICU at 617-355-8076. They can review criteria and fax you a parent information form.
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