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In infants with congenital heart disease autonomic dysfunction is associated with pre-operative brain injury

Abstract

Background

Brain injury is a serious and common complication of critical congenital heart disease (CHD). Impaired autonomic development (assessed by heart rate variability (HRV)) is associated with brain injury in other high-risk neonatal populations.

Objective

To determine whether impaired early neonatal HRV is associated with pre-operative brain injury in CHD.

Methods

In infants with critical CHD, we evaluated HRV during the first 24 h of cardiac ICU (CICU) admission using time-domain (RMS 1, RMS 2, and alpha 1) and frequency-domain metrics (LF, nLF, HF, nHF). Pre-operative brain magnetic resonance imaging (MRI) was scored for injury using an established system. Spearman’s correlation coefficient was used to determine the association between HRV and pre-operative brain injury.

Results

We enrolled 34 infants with median birth gestational age of 38.8 weeks (IQR 38.1–39.1). Median postnatal age at pre-operative brain MRI was 2 days (IQR 1–3 days). Thirteen infants had MRI evidence of brain injury. RMS 1 and RMS 2 were inversely correlated with pre-operative brain injury.

Conclusions

Time-domain metrics of autonomic function measured within the first 24 h of admission to the CICU are associated with pre-operative brain injury, and may perform better than frequency-domain metrics under non-stationary conditions such as critical illness.

Impact

  • Autonomic dysfunction, measured by heart rate variability (HRV), in early transition is associated with pre-operative brain injury in neonates with critical congenital heart disease.

  • These data extend our earlier findings by providing further evidence for (i) autonomic dysfunction in infants with CHD, and (ii) an association between autonomic dysfunction and brain injury in critically ill neonates.

  • These data support the notion that further investigation of HRV as a biomarker for brain injury risk is warranted in infants with critical CHD.

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Funding

Grant support for this project is from the Canadian Institute of Health Research, MOP-8111 and National Institutes of Health: NHLBI R01 HL116585-01.

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Authors and Affiliations

Authors

Contributions

S.D.S. designed the study, interpreted the data, and wrote the manuscript. R.B.G. performed HRV analysis for the study population and provided a critical review of the manuscript. J.M. interpreted and scored brain MRIs for brain injury and provided a critical review of the manuscript. S.D.B. performed statistical analyses for the study, interpreted the data, and provided a critical review of the manuscript. C.L. coordinated patient enrollment and clinical data acquisition and provided a critical review of the manuscript. M.T.D. interpreted patient echocardiograms, aided in study recruitment, and provided a critical review of the manuscript. S.B.M. provided a critical review of the manuscript and provided HRV data on subjects. C.L. designed the study with S.D.S. and A.J.d.P., provided MRI data on study subjects, and provided a critical review of the manuscript. A.J.d.P. designed the study and provided a critical review of the manuscript.

Corresponding author

Correspondence to Sarah D. Schlatterer.

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The authors declare no competing interests.

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The Institutional Review Board of Children’s National Hospital approved this study and written informed consent was obtained from each participant.

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Schlatterer, S.D., Govindan, R.B., Murnick, J. et al. In infants with congenital heart disease autonomic dysfunction is associated with pre-operative brain injury. Pediatr Res 91, 1723–1729 (2022). https://doi.org/10.1038/s41390-021-01931-7

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  • DOI: https://doi.org/10.1038/s41390-021-01931-7

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