Elevated temperature and 6- to 7-year outcome of neonatal encephalopathy

Abstract

Objective: A study was undertaken to determine whether higher temperature after hypoxia-ischemia is associated with death or intelligence quotient (IQ)<70 at 6 to 7 years among infants treated with intensive care without hypothermia.

Methods: Control infants (noncooled, n=106) of the National Institute of Child Health and Human Development Neonatal Research Network hypothermia trial had serial esophageal and skin temperatures over 72 hours. Each infant's temperature was ranked to derive an average of the upper and lower quartile, and median of each site. Temperatures were used in logistic regressions to determine adjusted associations with death or IQ<70 at 6 to 7 years. Secondary outcomes were death, IQ<70, and moderate/severe cerebral palsy (CP). IQ and motor function were assessed with Wechsler Scales for Children and Gross Motor Function Classification System. Results are odds ratio (OR; per degree Celsius increment within the quartile or median) and 95% confidence interval (CI).

Results: Primary outcome was available for 89 infants. At 6 to 7 years, death or IQ<70 occurred in 54 infants (37 deaths, 17 survivors with IQ<70) and moderate/severe CP in 15 infants. Death or IQ<70 was associated with the upper quartile average of esophageal (OR=7.3, 95% CI=2.0-26.3) and skin temperature (OR=3.5, 95% CI=1.2-10.4). CP was associated with the upper quartile average of esophageal (OR=12.5, 95% CI=1.02-155) and skin temperature (OR=10.3, 95% CI=1.3-80.2).

Interpretation: Among noncooled infants of a randomized trial, elevated temperatures during the first postnatal days are associated with increased odds of a worse outcome at 6 to 7 years.

Figure 1

Cohort diagram indicating the number of infants randomized to the non-cooled control group and those that were part of this investigation. Temp = temperature, FU = follow up, IQ = intelligence quotient

Figure 2

This plot displays the distribution of the non-cooled control infants among 0·5°C strata of esophageal temperature along the horizontal axis and the number of infants along the vertical axis. Interval notation is used along the horizontal axis where brackets are used to show inclusion and parentheses are used to indicate exclusion. The top, middle and lower panels display the results for the average of the highest quartile, the median and the average of the lowest quartile of esophageal temperature, respectively.