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.
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.
Hi Keith. Hope to see you at the PAS next week. The NICHD NRN has also developed a prognostic classification system using MRI after HIE (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3722585/). I think the big question is how much the scan actually adds to a good physical exam and readily available clinical data. We have developed scoring systems using just data available in the first 6 hours (http://www.ncbi.nlm.nih.gov/pubmed/17079582) that are quite accurate.
Thanks for the comment, and for the great work you are doing. I agree entirely, and I probably didn’t say it clearly enough: for an early MRI to be worthwhile (as a routine clinical tool) it has to add something substantial to what we can already get with a clinical exam and a review of the history. So far, I am not sure that there is much added value, even those these new studies suggest you don’t need to wait a week to have a reliable MRI, they don’t answer the question of whether an MRI adds anything to routine clinical care.
My guess is that they probably do, but that the added information is more at the level of giving more detailed information, but not necessarily with enough precision to enable us to make the right decision, when decision making is critical.
Would love to partner with you more….I represent Hope for HIE, a worldwide network of families whose children have experienced HIE. I am responsible for professional outreach for the organization.