Heart rate variability is associated with self-regulation and stress neurobehavior in preterm infants

E L. Donnellan, Developing Brain Institute, Children's National Hospital, Washington, DC, USA.
R B. Govindan, Developing Brain Institute, Children's National Hospital, Washington, DC, USA; Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, USA; The Zickler Family Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, USA.
J Ngwa, Developing Brain Institute, Children's National Hospital, Washington, DC, USA; Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, USA.
N Andescavage, Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, USA; Division of Neonatology, Children's National Hospital, Washington, DC, USA.
C Limperopoulos, Developing Brain Institute, Children's National Hospital, Washington, DC, USA; Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, USA; The Zickler Family Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, USA.
A J. du Plessis, Developing Brain Institute, Children's National Hospital, Washington, DC, USA; Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, USA; The Zickler Family Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, USA; Department of Neurology School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA. Electronic address: adupless@childrensnational.org.

Document Type

Journal Article

Publication Date

9-29-2025

Journal

Early human development

Volume

211

DOI

10.1016/j.earlhumdev.2025.106406

Keywords

Detrended fluctuation analysis; Heart rate variability; Neonatal intensive care unit; Preterm; Self-regulation; Stress

Abstract

BACKGROUND: The NICU (neonatal intensive care unit) Network Neurobehavioral Scale (NNNS) quantitatively assesses several distinct neurobehavioral domains. Neurobehavioral states interface with the autonomic nervous system. We sought to determine if autonomic tone, measured by heart rate variability (HRV), is associated with performance on NNNS neurobehavioral subscales. METHODS: Using continuous electrocardiogram recordings, we derived the following HRV measures: short (α1), and long-term (α2) fractal scaling exponents and short (RMS1) and long-term (RMS2) root mean square fluctuations. The NNNS was completed around term equivalent age (TEA). Linear mixed effects models tested associations between six NNNS subscales and HRV metrics. Secondary analyses explored the role of postmenstrual age (PMA) on associations between NNNS and HRV. These associations were further tested in the earliest and latest postnatal NICU weeks for each infant. RESULTS: We enrolled 39 premature infants (birth gestational age 23-36 weeks). Several HRV metrics were associated with Self-Regulation and Stress. After controlling for common NICU exposures (i.e. ventilation, steroids, caffeine and antibiotics), self-regulation was positively associated with alpha1 and RMS1 (standardized β = 0.262-0.284). Stress was associated negatively with alpha1 and RMS1 (standardized β = -0.283 to -0.286) and positively with alpha2 (standardized β = 0.245). Associations between Self-Regulation and Stress on RMS1 differed by PMA and NICU week, respectively. α1 and α2 at TEA predicted Stress (AUC = 0.730-0.775). CONCLUSION: Of the six subscales examined, only Stress and Self-Regulation scores were associated with autonomic metrics in preterm infants. For short-term autonomic fluctuations, PMA and NICU week influenced this relationship. Furthermore, the fractal scaling exponents predict abnormal Stress scores.

Department

Pediatrics

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