Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy.
BACKGROUND
Hypothermia is protective against brain injury after asphyxiation in animal models. However, the safety and effectiveness of hypothermia in term infants with encephalopathy is uncertain.


METHODS
We conducted a randomized trial of hypothermia in infants with a gestational age of at least 36 weeks who were admitted to the hospital at or before six hours of age with either severe acidosis or perinatal complications and resuscitation at birth and who had moderate or severe encephalopathy. Infants were randomly assigned to usual care (control group) or whole-body cooling to an esophageal temperature of 33.5 degrees C for 72 hours, followed by slow rewarming (hypothermia group). Neurodevelopmental outcome was assessed at 18 to 22 months of age. The primary outcome was a combined end point of death or moderate or severe disability.


RESULTS
Of 239 eligible infants, 102 were assigned to the hypothermia group and 106 to the control group. Adverse events were similar in the two groups during the 72 hours of cooling. Primary outcome data were available for 205 infants. Death or moderate or severe disability occurred in 45 of 102 infants (44 percent) in the hypothermia group and 64 of 103 infants (62 percent) in the control group (risk ratio, 0.72; 95 percent confidence interval, 0.54 to 0.95; P=0.01). Twenty-four infants (24 percent) in the hypothermia group and 38 (37 percent) in the control group died (risk ratio, 0.68; 95 percent confidence interval, 0.44 to 1.05; P=0.08). There was no increase in major disability among survivors; the rate of cerebral palsy was 15 of 77 (19 percent) in the hypothermia group as compared with 19 of 64 (30 percent) in the control group (risk ratio, 0.68; 95 percent confidence interval, 0.38 to 1.22; P=0.20).


CONCLUSIONS
Whole-body hypothermia reduces the risk of death or disability in infants with moderate or severe hypoxic-ischemic encephalopathy.
Shankaran
Seetha
S
Division of Neonatal-Perinatal Medicine, Wayne State University, Children's Hospital of Michigan, Detroit, MI 48201, USA. sshankar@med.wayne.edu
Laptook
Abbot R
AR
Ehrenkranz
Richard A
RA
Tyson
Jon E
JE
McDonald
Scott A
SA
Donovan
Edward F
EF
Fanaroff
Avroy A
AA
Poole
W Kenneth
WK
Wright
Linda L
LL
Higgins
Rosemary D
RD
Finer
Neil N
NN
Carlo
Waldemar A
WA
Duara
Shahnaz
S
Oh
William
W
Cotten
C Michael
CM
Stevenson
David K
DK
Stoll
Barbara J
BJ
Lemons
James A
JA
Guillet
Ronnie
R
Jobe
Alan H
AH
D000138:Acidosis / Q000209:etiology; D001238:Asphyxia Neonatorum / Q000150:complications; D001766:Blindness / Q000517:prevention & control; D002547:Cerebral Palsy / Q000517:prevention & control*; D002658:Developmental Disabilities / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D034381:Hearing Loss / Q000517:prevention & control; D006801:Humans; D007036:Hypothermia, Induced / Q000009:adverse effects; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000401:mortality / Q000628:therapy*; D007231:Infant, Newborn; D008297:Male; D007744:Obstetric Labor Complications; D011247:Pregnancy; D011248:Pregnancy Complications