The hypothesis is that premature infants' can have enough cooling applied to cool their
brain to decrease CNS injury without cooling their body.
Hypoxic ischemic encephalopathy (HIE) is a potentially devastating disease of the newborn
central nervous system (CNS) . Portions of the CNS are deprived of oxygen and blood flow for
a period of time which may lead to permanent brain injury manifested as cerebral palsy as
well as cognitive defects. Until recently no treatment has been shown to be effective for
preventing brain damage, even though it has been demonstrated that the damage is progressive
and that there is a window of opportunity to arrest some of the evolving brain injury.
However, in May of 2007 the FDA approved the first device specifically designed to
ameliorate brain damage in term babies with HIE. This head cooling device which was studied
here at Vanderbilt under IRB protocol 990129 Brain Cooling for the treatment of perinatal
hypoxic ischemic encephalopathy. We thus have eight years of experience of using this device
in term infants. The results of the initial trial demonstrated a successful reduction of HIE
induced brain injury from 66% in control infants to 55% in treated babies. There were no
significant risks to the application of this device in term babies who are kept cool for 72
hours after experiencing an acute HIE event. The initial trials were limited to term babies
because of concern that premature infants would be more at risk for hypothermia induced
problems such as hypoglycemia,and coagulopathy. The concern about hypothermia in preterm
infants remains a limiting consideration for doing whole body cooling in this population. We
propose to apply the cooling cap to the heads of preterm infants who have experienced a
significant HIE injury but maintain their body temperature in the normal range (36.1-37° C
rectally). Infants will be cooled for up to 72 hours and will be tracked till discharge.
Although this is a feasibility study, the participants will also be followed-up at 6, 12 and
24 months of age.
- Babies < 36 weeks gestation but > 32 0/7 weeks. These babies should be small enough
to allow brain cooling with water circulating in a cooling cap applied to the surface
of their head
- At least one of the following four criteria which are standard definitions for HIE:
- Apgar 0-3 at 1,5,10 minutes due to hypoxia
- pH less than 7.0
- Base deficit greater than 15
- Need for continued resuscitation due to hypoxia at 10 minutes
- AND a physical exam with evidence of hypotonia or lethargy or seizures indicative of
- Age less than 6 hours
- Signed informed consent by parent / legal guardian
- Previous participant has been followed through 7 day head ultrasound.
- Mild HIE will not be cooled, therefore babies without hypotonia or lethargy and
babies who are not intubated will be excluded.
- Gestational age ≥ 36 weeks or < 32 weeks or less than 1200 grams.
- Older than 6 hours of age
- Infant deemed in extremis on clinical exam.
- Survival not expected, i.e. received 3 intravenous doses of epinephrine or more
during resuscitation; on infusion of dopamine, dobutamine and/or epinephrine at time
of evaluation; and/or has fixed/dilated pupils.
- Evidence of head trauma or skull fracture causing major intracranial hemorrhage
- Intraventricular hemorrhage
- Weight less than the 5th percentile for gestational age
- Refusal of consent
- Imperforate anus