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N Engl J Med. 2012 May 31;366(22):2085-92. doi: 10.1056/NEJMoa1112066.

Childhood outcomes after hypothermia for neonatal encephalopathy.

Collaborators (135)

Jobe AH, Caplan MS, Laptook AR, Oh W, Hensman AM, Noel L, Watson VE, Walsh MC, Fanaroff AA, Bass N, Friedman HG, Newman NS, Siner BS, Schibler K, Donovan EF, Bridges K, Steichen JJ, Alexander B, Grisby C, Mincey HL, Hessling J, Gratton TL, Goldberg RN, Cotten C, Gustafson KE, Auten KJ, Foy KA, Fisher KA, Grimes S, Lohmeyer MB, Stoll BJ, Carlton DP, Jain L, Blackwelder AM, Hale EC, Fritz S, Wright LL, McClure EM, Archer SW, Poindexter BB, Lemons JA, Appel DD, Bissey J, Herron DE, Miller LC, Richard L, Wilson LD, Poole W, Auman JO, Cunningham M, Hastings BK, Newman JE, Schaefer SE, Zaterka-Baxter KM, Van Meurs KP, Stevenson DK, Ball M, DeAnda ME, Carlo WA, Ambalavanan N, Nelson KG, Collins MV, Cosby SS, Phillips VA, Smith LL, Fuller MG, West R, Finer NN, Kaegi D, Rasmussen MR, Arnell K, Henderson C, Rich W, Duara S, Hiriart-Fajardo S, Allison M, Calejo M, Everett-Thomas R, Eguaras SM, Gauthier S, Phelps DL, Myers GJ, Hust D, Reubens LJ, Sánchez PJ, Broyles R, Laptook AR, Rosenfeld CR, Salhab WA, Heyne RJ, Boatman C, Dooley C, Hensley G, Hickman JF, Leps MH, Madison S, Miller NA, Morgan JS, Torres LE, Guzman A, Tyson JE, Kennedy KA, Akpa EG, Cluff PA, Franco CI, Lis AE, McDavid GE, Tate PL, Alaniz NI, Bradt PJ, Cedillo M, Dieterich S, Evans PW, Green C, Jiminez M, Major-Kincade T, Morris BH, Poundstone M, Reddoch S, Siddiki S, Simmons MC, Whitely LL, Wright SL, Valdés LM, Johnson YR, Goldston LA, Muran G, Kennedy D, Pruitt PJ, Gettner P, Konstantino M, Poulsen J, Romano E, Williams J, DeLancy S.

Author information

Department of Pediatrics, Wayne State University, Detroit, MI, USA.

Erratum in

  • N Engl J Med. 2012 Sep 13;367(11):1073.



We previously reported early results of a randomized trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy showing a significant reduction in the rate of death or moderate or severe disability at 18 to 22 months of age. Long-term outcomes are now available.


In the original trial, we assigned infants with moderate or severe encephalopathy to usual care (the control group) or whole-body cooling to an esophageal temperature of 33.5°C for 72 hours, followed by slow rewarming (the hypothermia group). We evaluated cognitive, attention and executive, and visuospatial function; neurologic outcomes; and physical and psychosocial health among participants at 6 to 7 years of age. The primary outcome of the present analyses was death or an IQ score below 70.


Of the 208 trial participants, primary outcome data were available for 190. Of the 97 children in the hypothermia group and the 93 children in the control group, death or an IQ score below 70 occurred in 46 (47%) and 58 (62%), respectively (P=0.06); death occurred in 27 (28%) and 41 (44%) (P=0.04); and death or severe disability occurred in 38 (41%) and 53 (60%) (P=0.03). Other outcome data were available for the 122 surviving children, 70 in the hypothermia group and 52 in the control group. Moderate or severe disability occurred in 24 of 69 children (35%) and 19 of 50 children (38%), respectively (P=0.87). Attention-executive dysfunction occurred in 4% and 13%, respectively, of children receiving hypothermia and those receiving usual care (P=0.19), and visuospatial dysfunction occurred in 4% and 3% (P=0.80).


The rate of the combined end point of death or an IQ score of less than 70 at 6 to 7 years of age was lower among children undergoing whole-body hypothermia than among those undergoing usual care, but the differences were not significant. However, hypothermia resulted in lower death rates and did not increase rates of severe disability among survivors. (Funded by the National Institutes of Health and the Eunice Kennedy Shriver NICHD Neonatal Research Network; number, NCT00005772.).

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