Functional brain connectivity in early adolescence after hypothermia-treated neonatal hypoxic-ischemic encephalopathy

Aim Neonatal hypoxic-ischemic encephalopathy (HIE) injures the infant brain during the basic formation of the developing functional connectome. This study aimed to investigate long-term changes in the functional connectivity (FC) networks of the adolescent brain following neonatal HIE treated with therapeutic hypothermia (TH). Method This prospective, population-based cohort study included all infants (n=66) with TH-treated neonatal HIE in Stockholm during 2007-2009 and a control group (n=43) of children with normal neonatal course. Assessment with resting-state functional magnetic resonance imaging (fMRI) was performed at Karolinska Institutet, Stockholm at age 9-12 years. Results fMRI data met quality criteria for 35 children in the HIE-cohort (mean [SD] age at MRI: 11.2 [0.74] years, 46% male) and 30 children in the control group (mean [SD] age at MRI: 10.1 [0.78] years, 53% male). Clinical neurologic symptoms were present in 40% of children in the HIE-cohort. Non-parametric statistical analysis failed to detect any significant (p<0.001) alterations of FC networks in the HIE-cohort, nor between children in the HIE-cohort with or without neurological sequelae. Interpretation HT-treated HIE could not be associated with persistent alteration of the functional connectome. This indicates a notable resilience of the functional architecture of the brain against this type of early brain injury.