Posthypoxic
therapeutic hypothermia has been tested in newborn infants, with seven randomized trials showing consistent evidence of reduction in death,
cerebral palsy, and
cognitive impairment at school age. In contrast, randomized trials of
hypothermia after
cardiac arrest in adults have not shown consistent evidence of lasting neurological protection. The apparently greater effectiveness of
therapeutic hypothermia in newborns may be due to important
biological and clinical differences. One such difference is that adults are heavily colonized with microbes, and many have active inflammatory processes at the time of arrest, but few newborns are heavily colonized or infected at the time of birth.
Inflammation can interfere with
hypothermia's neuroprotection. A second difference is that apoptosis is more commonly the pathway of neuronal death in newborns than in adults.
Hypothermia inhibits apoptosis but not
necrosis. Newborns have a larger endogenous supply of stem cells (which reduce apoptosis) than adults and this may favor regeneration and protection from
hypothermia and regeneration. A third difference is that immature oligodendroglia are more sensitive to
free radical attack then mature oligodendroglia.
Hypothermia reduces
free radical release. In addition, immature brain has increased
N-methyl-D-aspartate receptor subunits compared with adults and
hypothermia reduces excitotoxic
amino acids. Adults suffering
cardiac arrest often have comorbidities such as diabetes,
hypertension, and
atherosclerosis, which complicate recovery, but newborn infants rarely have comorbidities before
asphyxia. Adult
hypothermia treatment may have been too short as no trial has cooled for longer than 48 hours, some only 24 or 12 hours, but neonatal
therapeutic hypothermia has routinely lasted 72 hours. We hypothesize that this combination of differences favors the effectiveness of
therapeutic hypothermia in newborn infants compared with adults.