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  • Clinical Research Article
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Bedside tracking of functional autonomic age in preterm infants

Pediatric Research volume 94, pages 206–212 (2023)Cite this article

Abstract

Background

Preterm birth predisposes infants to adverse outcomes that, without early intervention, impacts their long-term health. To assist bedside monitoring, we developed a tool to track the autonomic maturation of the preterm by assessing heart rate variability (HRV) changes during intensive care.

Methods

Electrocardiogram (ECG) recordings were longitudinally recorded in 67 infants (26–38 weeks postmenstrual age (PMA)). Supervised machine learning was used to generate a functional autonomic age (FAA), by combining 50 computed HRV features from successive 5-minute ECG epochs (median of 23 epochs per infant). Performance of the FAA was assessed by correlation to PMA, clinical outcomes and the infant’s functional brain age (FBA), an index of maturation derived from the electroencephalogram.

Results

The FAA was strongly correlated to PMA (r = 0.86, 95% CI: 0.83–0.93) with a mean absolute error (MAE) of 1.66 weeks and also accurately estimated FBA (MAE = 1.58 weeks, n = 54 infants). The relationship between PMA and FAA was not confounded by neurodevelopmental outcome (p = 0.18, n = 45), sex (p = 0.88, n = 56), patent ductus arteriosus (p = 0.08, n = 56), IVH (p = 0.63, n = 56) or body weight at birth (p = 0.95, n = 56).

Conclusions

The FAA, an index derived from the ubiquitous ECG signal, offers direct avenues towards estimating autonomic maturation at the bedside during intensive care monitoring.

Impact

  • The development of a tool to track functional autonomic age in preterm infants based on heart rate variability features in the electrocardiogram provides a rapid and specialized view of autonomic maturation at the bedside.

  • Functional autonomic age is linked closely to postmenstrual age and central nervous system function response, as determined by its relationship to functional brain age from the electroencephalogram.

  • Tracking functional autonomic age during neonatal intensive care unit monitoring offers a unique insight into cardiovascular health in infants born extremely preterm and their maturational trajectories to term age.

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Fig. 1: Overview of the study.
Fig. 2: FAA and PMA relationships following extremely preterm birth.

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Data availability

Code for processing an ECG epoch to estimate FAA, along with the trained data model, can be found here: https://github.com/brain-modelling-group/Estimate-FAA.

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Funding

This study was supported by an NHMRC Grant no. 2002135.

Author information

Authors and Affiliations

  1. QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia

    Kartik K. Iyer, Unnah Leitner, James A. Roberts & Nathan J. Stevenson

  2. School of Medicine and Dentistry, Griffith University, Gold Coast, QLD, 4215, Australia

    Unnah Leitner

  3. Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Department of Pediatrics, Comprehensive Center for Paediatrics (CCP), Medical University of Vienna, Vienna, Austria

    Vito Giordano & Katrin Klebermass-Schrehof

  4. BABA Center, Departments of Physiology and Clinical Neurophysiology, Pediatric Research Center, Children’s Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

    Sampsa Vanhatalo

Authors
  1. Kartik K. Iyer
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Contributions

K.K.I., N.J.S., V.G., S.V., and K.K.-S. conceptualized the design of the study and overall motivations of the study. V.G., U.L., and K.K.-S. assisted with data collection, curation, and resources necessary for investigation. K.K.I. and N.J.S. processed, analyzed, and interpreted the data. S.V., K.K.-S., and V.G. further assisted with the clinical interpretations. K.K.I., N.J.S., and S.V. wrote and edited the draft of the manuscript. K.K.-S., J.A.R., V.G., and U.L. contributed substantially to the manuscript and provided critical revisions.

Corresponding author

Correspondence to Kartik K. Iyer.

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The authors declare no competing interests.

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Informed parental consent was obtained for all infants included in the study.

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Iyer, K.K., Leitner, U., Giordano, V. et al. Bedside tracking of functional autonomic age in preterm infants. Pediatr Res 94, 206–212 (2023). https://doi.org/10.1038/s41390-022-02376-2

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