Severity of hypoxic ischemic encephalopathy and heart rate variability in neonates: a systematic review

Abstract

Background Several studies have investigated heart rate variability (HRV) as a biomarker for acute brain injury in hypoxic ischemic encephalopathy (HIE). However, the current evidence is heterogeneous and needs further reviewing to direct future studies. We aimed to systematically review whether HIE severity is associated with HRV. Methods This systematic review was conducted according to the preferred reporting items for systematic review and meta analyses (PRISMA). We included studies comparing neonates with severe or moderate HIE with neonates with mild or no HIE with respect to different HRV measures within 7 days of birth. Article selection and quality assessment was independently performed by two reviewers. Risk of bias and strength of evidence was evaluated by the Newcastle-Ottawa scale (NOS) and the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results We screened 1187 studies. From these, four observational studies with 248 neonates were included. For all HRV measures, the strength of evidence was very low. Neonates with severe or moderate HIE showed a reduction in most HRV measures compared to neonates with mild or no HIE with a greater reduction in those with severe HIE. Conclusions Moderate and severe HIE was associated with a reduction in most HRV measures. Accordingly, HRV is a potential biomarker for HIE severity during the first week of life. However, the uncertainty calls for more studies. Electronic supplementary material The online version of this article (10.1186/s12887-019-1603-7) contains supplementary material, which is available to authorized users.

Heart Rate Variability in the Perinatal Period: A Critical and Conceptual Review

“…Therefore, the frequency-domain metrics could be biased from the beginning: this could be a reason why LF and HF do not reflect a specific physiologic function, but the interaction between PNS, SNS, and respiratory activity (Hayano and Yuda, 2019). Moreover, not all studies on newborns use the same thresholds for discriminating between LF and HF (Andersen et al, 2019).…”

“…Since HRV modifications correlated with inflammatory cytokine levels (Al-Shargabi et al, 2017), real-time HRV could be a useful marker of clinical acuity: indeed, HRV alterations-a decrease in RMS S , RMS L , DFA α S , LF, HF, and TP or an increase in HRC index-correlated with the pathology severity (Sullivan et al, 2014;Al-Shargabi et al, 2018). Variations in LF, HF, and LF/HF correlated with HIE severity, although more studies are needed to resolve conflicting results between studies (Andersen et al, 2019). In a recent paper on a pediatric population, compared with the time of admission in the intensive care units, RMSSD, SDNN, and pNN50 continuously rose as the time of discharge approached, that is, as the infants recovered (Marsillio et al, 2019).…”

“…Studies that continuously recorded HRV for more than 24 h, or that reviewed those recordings if available, led to discovering that HRV alteration can precede adverse outcomes even by 24 h ( Griffin and Moorman, 2001 ; Stone et al, 2013 ; Kumar et al, 2020 ). Many of the studies about the predictive power of real-time HRV, in particular, in case of infections, relied on the HeRO monitor ( Andersen et al, 2019 ; Kumar et al, 2020 ). The NIPE technology represents another attempt of introducing real-time HRV monitoring in NICUs, but it needs further evidence ( Weber et al, 2019 ; Zhang et al, 2019 ).…”

“…Notwithstanding these contradictions, the only successful example of integration of HRV in NICUs is the Heart Rate Observation (HeRO) monitor developed by J. Randall Moorman's team. The HeRO analyzes bedside electrocardiogram (ECG) in real-time and integrates various HRV metrics to calculate the "HRC index, " which can predict the risk of sepsis within 24 h in both preterms and very low birth weight infants (Andersen et al, 2019;Kumar et al, 2020).…”

Relationship between Brain Injury and Clinical Biomarkers in Hypoxic-Ischemic Newborn Piglets

“…This transient recovery is followed by a secondary deterioration involving a failure of oxidative metabolism (secondary phase) [5][6][7], which is associated with excitotoxic edema, seizures, cerebral hyperperfusion, and ultimately, brain cell death [8]. The term HIE is preferred over perinatal asphyxia [9], and clinical markers, such as fetal heart rate variability [10], blood gases from umbilical cord or Apgar scores, among others, are required to determine the risk of developing brain injury [11]. These clinical markers are currently being used in the clinical setting with approximately 80% sensitivity and specificity [12].…”