Elsevier

The Journal of Pediatrics

Volume 157, Issue 3, September 2010, Pages 367-372.e3
The Journal of Pediatrics

Original Article
Selective Head Cooling with Mild Systemic Hypothermia after Neonatal Hypoxic-Ischemic Encephalopathy: A Multicenter Randomized Controlled Trial in China

https://doi.org/10.1016/j.jpeds.2010.03.030Get rights and content

Objective

To investigate the efficacy and safety of selective head cooling with mild systemic hypothermia in hypoxic-ischemic encephalopathy (HIE) in newborn infants.

Study design

Infants with HIE were randomly assigned to the selective head cooling or control group. Selective head cooling was initiated within 6 hours after birth to a nasopharyngeal temperature of 34° ± 0.2°C and rectal temperature of 34.5° to 35.0°C for 72 hours. Rectal temperature was maintained at 36.0° to 37.5°C in the control group. Neurodevelopmental outcome was assessed at 18 months of age. The primary outcome was a combined end point of death and severe disability.

Results

One hundred ninety-four infants were available for analysis (100 and 94 infants in the selective head cooling and control group, respectively). For the selective head cooling and control groups, respectively, the combined outcome of death and severe disability was 31% and 49% (OR: 0.47; 95% CI: 0.26-0.84; P = .01), the mortality rate was 20% and 29% (OR:0.62; 95% CI: 0.32-1.20; P = .16), and the severe disability rate was 14% (11/80) and 28% (19/67) (OR: 0.40; 95% CI: 0.17-0.92; P = .01).

Conclusions

Selective head cooling combined with mild systemic hypothermia for 72 hours may significantly decrease the combined outcome of severe disability and death, as well as severe disability.

Section snippets

Methods

This study involved the participation of 12 children's hospitals or children's and women's health care centers. The protocol was designed by the neonatologists at Children's Hospital of Fudan University and a consensus was reached by the participating hospitals. Written informed consent was obtained from parents before enrollment. This study was approved by the ethics committee of the Children's Hospital of Fudan University.

Infants were screened for eligibility if they had a gestational age ≥

Results

From May 2003 to August 2005, a total of 256 cases were recruited. Figure 1 (available at www.jpeds.com) shows the trial profile. Twenty-one infants (19 and 2 infants in the selective head cooling and control group) were excluded because the pediatricians in the local hospitals did not follow the scheduled random methods.

Discussion

Hypothermia, whether whole body or selective head cooling, shows great promise on the basis of both animal and human neonatal studies.3, 4, 11, 12, 13, 14, 15 Three RCT trials demonstrated that hypothermia could improve the combined outcome of death and severe neurodevelopmental disability or an increased rate of survival without neurologic abnormality and reduced risks of cerebral palsy at 18 months of age.16, 17, 18 A recently published meta-analysis32 also showed the effectiveness of

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    Supported by grants from Construction of Key Disciplines of 211 Engineering of Ministry of Education of People's Republic of China. The authors declare no conflicts of interest.

    Registration number at Clinicaltrials.gov: NCT00890409.

    A list of members of The China Study Group is available at www.jpeds.com (Appendix).

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