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Timing of MRI after HIE

kbarrington

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Three recent articles have investigated whether we should wait until a week or so after birth to perform brain imaging in infants with encephalopathy, or whether earlier imaging might be just as predictive.

The three articles have consistent findings, which is remarkable in itself! All three note that infants at high risk, most of whom have undergone hypothermia treatment, when they have MRI at 2 to 4 days of age, the results are very similar to the findings if you wait until a week or so to do the study.

Agut T, et al. Early identification of brain injury in infants with hypoxic ischemic encephalopathy at high risk for severe impairments: accuracy of MRI performed in the first days of life. BMC Pediatrics. 2014;14(1):177.

Boudes E, et al. MRI obtained during versus after hypothermia in asphyxiated newborns. Archives of Disease in Childhood - Fetal and Neonatal Edition. 2015;100(3):F238-F42.

Skranes JH, et al. Brain imaging in cooled encephalopatic neonates does not differ between four and 11 days after birth. Acta Paediatrica. 2015.

Now I think you could say the same about many of these type of studies as about the studies of brain imaging in very preterm babies. Which is, that if the reason that you want to do the study is to aid in medical decision making (which is explicitly stated in the first of the 3 articles) we need much better data of the positive predictive value of the findings for profoundly adverse outcomes.

The best data I think come from the analysis of the TOBY trial, Rutherford M, et al. Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial. The Lancet Neurology. 2010;9(1):39-45. That study used a scoring system, created by the same group, and showed that the positive predictive value of moderate or severe lesions in the basal ganglia and thalami, severe white matter lesions, or an abnormal posterior limb of the internal capsule for death or severe disability at 18 months of age was 0·76 (95% CI 0·65–0·87).

Severe disability was defined as at least one of: mental development index (MDI) less than 70 (2 or more SD below the mean) on the Bayley infant scales (BSID II) at 2 years; cerebral palsy with a GMFCS of 3–5 (unlikely to be ambulant) or bilateral cortical visual impairment with no useful vision.

There is some evidence that a 2 year Bayley is more predictive of limited longer term functioning after HIE than it is for former extreme preterm infants, for example this article from the follow up of the NRN trial, Pappas A, et al. Cognitive outcomes after neonatal encephalopathy. Pediatrics. 2015;135(3):e624-34. Of 30 babies with a Bayley 2 MDI less than 70, 27 of them had a full scale IQ less than 70 at 6 to 7 years of age. (Most of the infants with an MDI less than 70 were below 55, 24 of the 30; also 23 of the 31 babies with an IQ below 70 were below 55).

If we put all this together it seems that it might be possible to have a reasonably accurate prediction of severely abnormal outcome using MRI shortly after, or even during the final day of, therapeutic hypothermia. I think before we rush to performing early MRI, and use them for decision making, we should have more, and more direct, evidence that a certain severity of abnormality on the early MRI, accurately predicts profound impairment, and that this is better than clinical examination, or other predictive indices.

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