Published online September 1, 2008
PEDIATRICS Vol. 122 No. 3 September 2008, pp. 491-499 (doi:10.1542/peds.2007-1673)

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ARTICLE

Elevated Temperature After Hypoxic-Ischemic Encephalopathy: Risk Factor for Adverse Outcomes

Abbot Laptook, MD^a, Jon Tyson, MD, MPH^b, Seetha Shankaran, MD^c, Scott McDonald, BS^d, Richard Ehrenkranz, MD^e, Avroy Fanaroff, MD^f, Edward Donovan, MD^g, Ronald Goldberg, MD^h, T. Michael O'Shea, MDⁱ, Rosemary D. Higgins, MD^j, W. Kenneth Poole, PhD^d and the National Institute of Child Health and Human Development Neonatal Research Network

^a Department of Pediatrics, Women and Infants' Hospital of Rhode Island, Providence, Rhode Island
^b Department of Pediatrics, University of Texas Medical School at Houston, Houston, Texas
^c Department of Pediatrics, Wayne State University, Detroit, Michigan
^d Department of Statistics and Epidemiology, RTI International, Research Triangle Park, North Carolina
^e Department of Pediatrics, Yale University, New Haven, Connecticut
^f Department of Pediatrics, Case Western University, Cleveland, Ohio
^g Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio
^h Department of Pediatrics, Duke University, Durham, North Carolina
ⁱ Department of Pediatrics, Wake Forest University, Winston-Salem, North Carolina
^j National Institute of Child Health and Human Development, Bethesda, Maryland

OBJECTIVE. The goal was to determine whether the risk of death or moderate/severe disability in term infants with hypoxic-ischemic encephalopathy increases with relatively high esophageal or skin temperature occurring between 6 and 78 hours after birth.

METHODS. This was an observational secondary study within the National Institute of Child Health and Human Development Neonatal Research Network randomized trial comparing whole-body cooling and usual care (control) for term infants with hypoxic-ischemic encephalopathy. Esophageal and skin temperatures were recorded serially for 72 hours. Each infant's temperatures for each site were rank ordered. The high temperature was defined for each infant as the mean of all temperature measurements in the upper quartile. The low temperature was similarly defined as the mean of the lower quartile. Outcomes were related to temperatures in 3 logistic regression analyses for the high, median, and low temperatures at each temperature site for each group, with adjustment for the level of encephalopathy, gender, gestational age, and race.

RESULTS. In control infants, the mean esophageal temperature was 37.2 ± 0.7°C over the 72-hour period, and 63%, 22%, and 8% of all temperatures were >37°C, >37.5°C, and >38°C, respectively. The mean skin temperature was 36.5 ± 0.8°C, and 12%, 5%, and 2% of all temperatures were >37°C, >37.5°C, and >38°C, respectively. The odds of death or disability were increased 3.6–4 fold for each 1°C increase in the highest quartile of skin or esophageal temperatures. There were no associations between temperatures and outcomes in the cooling-treated group.

CONCLUSIONS. Relatively high temperatures during usual care after hypoxia-ischemia were associated with increased risk of adverse outcomes. The results may reflect underlying brain injury and/or adverse effects of temperature on outcomes.

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Key Words: hypoxic-ischemic encephalopathy • neurologic outcome • temperature

Abbreviations: OR—odds ratio • CI—confidence interval • IL—interleukin

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Accepted Dec 13, 2007.

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