Send letter to journal:
Re: Palliation bias is being overlooked in neonatal hypothermia trials

Dear Editor,

I thank Drs Edwards and Azzopardi for their review (1) of the trials of therapeutic hypothermia following perinatal asphyxia (2-4). Unfortunately, the evaluation of data quality fails to acknowledge a major shortcoming common to all three reported trials-"palliation bias". There is a clear palliation bias in the control arm that completely invalidates the use of death as an outcome measure, be it singly or in the composite including disability. The efficacy study reported by Eicher at al (2) is the only one that gives some account of the contribution that withdrawal of care makes to the death statistic, and it serves well to demonstrate that this is highly significant. The criteria for withdrawal of care are not standardized and can be assumed to vary with differences in philosophy across units and between care-givers. More importantly, two factors must be recognized that will erroneously inflate the death rate in the control arm: (a) that there is a commitment to treatment for 72 hours in the cooling arm which discourages early withdrawal in the ventilator-dependent infant and (b) that parents who agree to participate in the trial are primed by a consent process that underlines the prospect of benefit in the presence of treatment. It is also incorrect to assume that the addition of disability to form the composite outcome will buffer this problem by taking into account the disability rate in the "extra survivors."

Dr Adrian J A Ziino, Sunnybrook and Women's College Health Sciences Centre, Toronto, CANADA.

References

1)Edwards AD and Azzopardi DV. Therapeutic hypothermia following perinatal asphyxia. Arch Dis Child Fetal Neonatal Ed 91: F127-131, 2006.

2)Eicher DJ, Wagner CL, Katikaneni LP, Hulsey TC, Bass WT, Kaufman DA, Horgan MJ, Languani S, Bhatia JJ, Givelichian LM, Sankaran K, and Yager JY. Moderate hypothermia in neonatal encephalopathy: efficacy outcomes. Pediatr Neurol 32: 11-17, 2005.

3)Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, and Gunn AJ. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 365: 663-670, 2005.

Send letter to journal:
Re: Re: Therapeutic hypothermia following perinatal asphyxia

Dear Editor,

The article written by Edwards and Azzopadi is excellent(1).Hypothermia is proving to be the therapy of choice for neonates with perinatal asphyxia(2,4).Not only is there benefit to the babies at 18 months of age but it is beneficial in the neonatal period also.We at Sherikashmir institute of medical sciences Soura Srinagar India studied 20 neonates with severe perinatal asphyxia who received whole body hypothermi and 15 neonates who served as controls.Randomisation was done by computer generated random numbers.In babies with hypothermia skin and rectal temperatures were maintained at 33.5 degree centigrade for 72 hours followed by slow rewarming.The main aims of the study were to look for death/abnormal neurological examination at the time of discharge.Although there were no significant differences between the patients who died in the two groups(15%vs.33%,p>.05),hypothermic neonates were less likely to have abnormal neurological examination at discharge (p<.001).The study proves that whole body hypothermia can be beneficial in the immediate neonatal period also and in combination with other therapies can reduce the chances of having neurodevelopmental delay at 18 months of age.

References

1)Edwards AD and Azzopardi DV. Therapeutic hypothermia following perinatal asphyxia. Arch Dis Child Fetal Neonatal Ed 91: F127-131, 2006.

2)Eicher DJ, Wagner CL, Katikaneni LP, Hulsey TC, Bass WT, Kaufman DA, Horgan MJ, Languani S, Bhatia JJ, Givelichian LM, Sankaran K, and Yager JY. Moderate hypothermia in neonatal encephalopathy: efficacy outcomes. Pediatr Neurol 32: 11-17, 2005.

3)Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, and Gunn AJ. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 365: 663-670, 2005.

Send letter to journal:
Re: Author's Response: Re: Palliation bias is being overlooked in neonatal hypothermia trials

Dear Editor,