Fetal heart rate variability is a biomarker of rapid but not progressive exacerbation of inflammation in preterm fetal sheep

Abstract

Perinatal infection/inflammation can trigger preterm birth and contribute to neurodevelopmental disability. There are currently no sensitive, specific methods to identify perinatal infection. We investigated the utility of time, frequency and non-linear measures of fetal heart rate (FHR) variability (FHRV) to identify either progressive or more rapid inflammation. Chronically instrumented preterm fetal sheep were randomly assigned to one of three different 5d continuous i.v. infusions: 1) control (saline infusions; n = 10), 2) progressive lipopolysaccharide (LPS; 200 ng/kg over 24 h, doubled every 24 h for 5d, n = 8), or 3) acute-on-chronic LPS (100 ng/kg over 24 h then 250 ng/kg/24 h for 4d plus 1 μg boluses at 48, 72, and 96 h, n = 9). Both LPS protocols triggered transient increases in multiple measures of FHRV at the onset of infusions. No FHRV or physiological changes occurred from 12 h after starting progressive LPS infusions. LPS boluses during the acute-on-chronic protocol triggered transient hypotension, tachycardia and an initial increase in multiple time and frequency domain measures of FHRV, with an asymmetric FHR pattern of predominant decelerations. Following resolution of hypotension after the second and third LPS boluses, all frequencies of FHRV became suppressed. These data suggest that FHRV may be a useful biomarker of rapid but not progressive preterm infection/inflammation.

Heart Rate as a Non-Invasive Biomarker of Inflammation: Implications for Digital Health

“…The starting point forms the recent study by Magawa et al. ( 1 ) In this study the authors validated and extended the initial observations by Durosier et al. and Herry et al.…”

Increased variability of fetal heart rate during labour: a review of preclinical and clinical studies

“…116,117 This increase in FHRV, however, is only observed after an acute inflammatory stimulus that triggers a rapid inflammatory and cardiovascular response, whereas a stable inflammation response has little effect on FHRV even if prolonged. 118 In two recent studies, 4% (nine of 224) 119 and 33% (four of 12) 120 of human fetuses of COVID-19 parturients showed the ZigZag pattern in CTG tracing. Similarly, chorioamnionitis and funisitis have been associated with the ZigZag pattern during labour.…”

“…In preterm fetal sheep, acute exposure to high‐dose lipopolysaccharide (a bacterial cell wall component that induces a systemic inflammatory response) triggered an increase in FHRV between 2 and 4 hours after exposure 116,117 . This increase in FHRV, however, is only observed after an acute inflammatory stimulus that triggers a rapid inflammatory and cardiovascular response, whereas a stable inflammation response has little effect on FHRV even if prolonged 118 . In two recent studies, 4% (nine of 224) 119 and 33% (four of 12) 120 of human fetuses of COVID‐19 parturients showed the ZigZag pattern in CTG tracing.…”

Validation of a new smart textiles biotechnology for heart rate variability monitoring in sheep

“…The differences reported above may be due to several reasons: first, it is difficult to compare HRV biometric parameters between different species because they may be characterized by different autonomic nervous system activity and different behavioral responses to humans ( 17 ). Comparison between sheep populations might be useful, however, literature especially focused on HRV monitoring in ovine fetus for human medicine purposes ( 24 – 26 ). Moreover, HRV evaluation might change dramatically due to the circumstances of the measurements, including the device used for the monitoring and the length of monitoring (long-term monitoring vs. short- or ultra-short-term monitoring) ( 51 ).…”