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Cooling therapy is associated with improved MR biomarker measures after mild neonatal encephalopathy

Presented at the Neonatal Society 2018 Spring Meeting (programme).

Montaldo P1, Oliveira V1, Soe A2, Kariholu U1, Atreja G1, Mendoza J1, Shankaran S3, Thayyil S1, Lally PJ2

1 Imperial College London, UK
2 Medway NHS Foundation Trust, UK
3 Wayne State University, USA

Background: While therapeutic hypothermia increases the likelihood of disability-free survival in moderate or severe neonatal encephalopathy (NE), its effects are unknown for infants with milder injury. Meanwhile, many centres have begun to offer therapeutic hypothermia as part of their standard care for babies with mild NE, using varying treatment durations. To evaluate the impact of therapeutic hypothermia in this specific sub-group, we measured metabolic and structural markers of brain injury using magnetic resonance (MR) imaging and spectroscopy, in babies with mild NE.

Methods: Consecutive term and near-term babies with NE who had therapeutic hypothermia were recruited from eight sites across the UK and USA over 3 years as part of the MARBLE study, and underwent MR imaging and spectroscopy at harmonised 3 Tesla MR scanners. MR biomarkers were reported by a researcher masked to the clinical information. Babies who did not receive cooling were excluded from the main study, but informed parental consent was obtained for inclusion in this sub-study.

Results: From the mild NE subgroup of the MARBLE study (n=41), 10 (24%) had received no cooling, 4 (10%) had received partial (<24h) cooling, and 27 (66%) had received complete (72h) cooling. Although fully cooled babies had significantly lower 10 min Apgar scores (p=0.004, Table 1)*, the thalamic ratios of N-acetylaspartate/creatine and Nacetylaspartate/ choline from MR spectroscopy were significantly higher in fully cooled babies than non-cooled babies (Figure 1a). On conventional MRI, the mean (SD) white matter injury scores in the non-cooled babies (1.3(0.7)) were significantly higher than in the fully cooled babies (0.5 (0.6), p=0.001). There was no difference in deep nuclei or cortical injury scores.

Conclusion: In this small cohort of mild encephalopathy, babies who were cooled for 72 hours had less brain injury than those who were cooled for 24h and those who were not cooled, both in terms of metabolic and structural MR biomarkers, despite lower Apgar score in the former. Future clinical trials should examine the optimal duration of cooling therapy in mild NE.

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