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

Background: 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).

Methods: 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). Adverse outcome was 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 symptoms.

Conclusion: Findings of persistent alterations in specific functional networks did not remain significant after correction for multiple comparisons in this cohort of adolescent children exposed to TH-treated neonatal HIE.

Impact: Neonatal hypoxic-ischemic encephalopathy (HIE) could not be associated with alterations in functional connectivity in this cohort of adolescent children. Findings of aberrant connectivity identified in two functional networks were no longer significant after correction for multiple comparisons. Larger, multi-center studies are needed to understand whether network abnormalities persist long term and are related to outcomes in neonatal HIE.