Transfer Entropy Modeling of Newborn Cardiorespiratory Regulation.

Maristella Lucchini,Nicolò Pini,Maria G Signorini,William P Fifer,Nina Burtchen

doi:10.3389/fphys.2020.01095

Abstract

This study investigates the complex interplay between the cardiac and respiratory systems in 268 healthy neonates born between 35 and 40 weeks of gestation. The aim is to provide a comprehensive description of the developing cardiorespiratory information transfer mechanisms as a function of gestational age (GA). This report proposes an extension of the traditional Transfer Entropy measure (TE), which employs multiple lagged versions of the time series of the intervals between two successive R waves of the QRS signal on the electrocardiogram (RR series) and respiration time series (RESP). The method aims to quantify the instantaneous and delayed effects between the two processes within a fine-grained time scale. Firstly, lagged TE was validated on a simulated dataset. Subsequently, lagged TE was employed on newborn cardiorespiratory data. Results indicate a progressive increase in information transfer as a function of gestational age, as well as significant differences in terms of instantaneous and delayed interactions between the cardiac and the respiratory system when comparing the two TE directionalities (RR→RESP vs. RESP→RR). The proposed investigation addresses the role of the different autonomic nervous system (ANS) branches involved in the cardiorespiratory system, since the sympathetic and parasympathetic branches operate at different time scales. Our results allow to infer that the two TE directionalities are uniquely and differently modulated by both branches of the ANS. TE adds an original quantitative tool to understanding cardiorespiratory imbalance in early infancy.

Highlights

Premature birth and related complications are the leading cause of death under 5 years of age across the world (Liu et al, 2016)
Given the Transfer Entropy measure (TE) formulation expressed in Eq 2, we computed TE based on a sequential procedure for non-uniform conditioning, where the conditioning vector is updated progressively by selecting the candidate which reduced the most uncertainty in explaining the target variable
Gaining insight on such interactions attains the potential for assessing individual differences in neonatal control mechanisms and vulnerability for the reported higher morbidity and mortality rates in LPT and early term (ET) newborns (Richards et al, 2016)

Summary

Introduction

Premature birth and related complications are the leading cause of death under 5 years of age across the world (Liu et al, 2016). Epidemiological studies have shown that late preterm [LPT: 340/7–366/7 weeks of gestational age (GA)] infants have significantly more. Data from a population study from 2006 to 2014 in the United States showed that LPT birth rate was 6%, while early term (ET: 370/7–386/7 GA) rate was 26.9% (Richards et al, 2016). Late preterm and early term birth are associated with adverse neonatal outcomes, such as higher incidence of respiratory distress syndrome, temperature instability, hypoglycemia, hyperbilirubinemia, apnea, feeding problems, as well as higher rates of re-hospitalization and a two-fold increase in Sudden Infant Death Syndrome (SIDS) (Thompson and Mitchell, 2006; Loftin et al, 2010; Adamkin, 2013). Frequent episodes of apneas, periodic breathing, altered pulmonary function, bradycardia, and diminished autonomic control of heart rate (HR) have been documented in these populations (Hunt, 2006; Scher et al, 2011; McEvoy et al, 2013; Lucchini et al, 2018)

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