Mild total body hypothermia, induced by cooling a baby to 33-34°C for three days after birth, is nowadays a standardized treatment after moderate to severe hypoxic ischemic encephalopathy in full-term and near to fullterm neonates.
The CoolCap study gathered data using the WeeFim questionnaire at 7–8 years of age, but only collected information on 62 (32 cooled; 30 standard care) of 135 surviving children who had had neurodevelopmental assessment at 18 months.
During mid gestation to late term the fetal brain is undergoing increasingly complex progressive growth of first the mid-brain and then development of the cortex and "higher" centers.
Since the prerequisites regarding immediate closeness after giving birth radically chances, researchers have become curious regarding parent's experiences and how to improve the nursing care around effects families.
Long-term follow-up has yet to demonstrate show persisting benefit, but available data together with an imaging study nested in TOBY also found reduced brain tissue damage in cooled infants are encouraging.
[9] The simplicity that attracted empiricists to cooling centuries ago now makes hypothermic neural rescue with accurate patient selection a potentially transforming therapy for low-resource environments where birth asphyxia remains a major cause of death and disability.
Experimental and clinical studies indicate that the number of apoptotic neurons is reduced caspase activity is lessened and cytochrome c translocation is diminished by mild hypothermia,[37][38] and there may be an increase in expression of the anti-apoptotic protein BCl-2.
[39] Many physicians over the centuries have tried to resuscitate babies after birth by altering their body temperatures, essentially aiming to animate the infant by inducing the onset of breathing.
[40] Little thought was given to brain protection, because cerebral hypoxia during birth was not linked with later neurological problems until William John Little in 1861,[41] and even then this was controversial; Sigmund Freud, for example, famously disagreed, and when scientific studies of neonatal therapeutic hypothermia were begun in the 1950s researchers like Bjorn Westin still reported their work in terms of re-animation rather than neuroprotection.
[42] Investigators such as James Miller and Clement Smith carried out clinical observations and careful physiological experiments,[43][44][45][46] but although some babies were conscientiously followed up, they were not mainly concerned with long term neurological outcome.
[50][51][52][53][54][55][56] Although across the Iron Curtain in the Soviet Union cooling was being applied empirically following birth asphyxia,[57] the language barrier, cold war politics and the Russians' failure to carry out randomised controlled trials contributed to an almost total ignorance of this work in the West.
These researchers were aware that cooling produced powerful intra-ischaemic neuroprotection during cardiac surgery but a new concept of hypothermic post-insult neural rescue developed.
The first paradigm shift that affected neonatal researchers in particular was the idea that if a baby was resuscitated after cerebral hypoxia-ischaemia there was a period of time before brain cells started to die.
Osmund Reynolds at University College London used the newly developed technique of Magnetic Resonance Spectroscopy (MRS) to show that the infant brain metabolism is normal in the hours after birth asphyxia and deteriorated only after a distinct delay.
If brain cells remained normal for a time and the mechanism of the delayed death could be unravelled, it opened the possibility of therapeutic intervention in what had previously seemed an impossible situation.
[66] They showed that at least some of the neural cell death caused by hypoxia-ischaemia is mediated by excess production of the excitatory neurotransmitter glutamate, and that pharmacological blockade of the N-methyl-D-aspartate receptor could provide good protection against hypoxic damage.
Denis Azzopardi, John Wyatt and David Edwards, then young researchers working for Reynolds, were using Reynolds's sophisticated MRS approach to replicate secondary energy failure in newborn piglets[28] and immature rats;[79] in Gluckman's laboratory Alistair Gunn and Chris Williams developed a simple and elegant biophysical method using cerebral impedance to do essentially the same thing in fetal sheep.