Depressed heart rate variability is associated with abnormal EEG, MRI, and death in neonates with hypoxic ischemic encephalopathy

Abstract

Objective: Asphyxia can lead to autonomic nervous system dysfunction, including depressed heart rate variability (HRV). We tested the hypothesis that low HRV is associated with adverse short-term outcomes of abnormalities on electroencephalogram (EEG) and brain magnetic resonance imaging (MRI) and death in neonates with hypoxic ischemic encephalopathy (HIE).

Study design: Neonates undergoing hypothermia therapy for HIE underwent monitoring of HRV. HRV in the first day after birth and after hypothermia and rewarming (days 4-7) were analyzed in relation to death and severity of abnormal findings on EEG and MRI.

Results: A total of 37 neonates had data available in the first 24 hour after birth and 67 had data days 2 to 7. Depressed HRV was significantly associated with adverse outcomes of death or moderate-to-severe abnormalities on EEG or MRI. In the first 24 hours, the odds ratio (OR) of one or more adverse outcomes for every 10-millisecond decrease in HRV was 3.19 (95% CI, 1.3-7.8; p = 0.01). HRV improved over time but low HRV remained significantly associated with adverse outcomes days 4 to 7 (OR, 2.72; CI, 1.32-5.61; p < 0.01).

Conclusions: Monitoring HRV, which is reflected in the heart rate characteristic index, may provide useful adjunct information on the severity of brain injury in infants with HIE.

Fig. 1

Heart rate characteristics (HRC) index monitor screen shots and concurrent electroencephalogram (EEG) tracings from three patients undergoing hypothermia therapy for hypoxic ischemic encephalopathy (HIE). The monitor top panel shows the 5-day trend in the HRC index (orange) and the bottom panel shows the last 30 minutes of HR (green, beats per minute). The current HRC index is displayed in the upper right panel. (A) HRC monitor on a patient with normal heart rate variability (HRV) reflected by a low HRC index of 0.25. The heart rate tracing shows normal frequent small accelerations and decelerations. EEG in the same time period shows mild encephalopathy (two tracings, 15 seconds of EEG each.) (B) HRC monitor on a patient with decreased HRV reflected by a higher HRC index of 3.05. There is reduction of HRV (few accelerations or decelerations). EEG in the same patient shows moderate encephalopathy (30 seconds, bottom panel) with cycling between awake and sleep states. (C) HRC monitor on a patient with severely decreased HRV reflected by a high HRC index of 7.00. The heart rate tracing shows absence of accelerations or decelerations. EEG in the same time period shows severe encephalopathy (30 seconds, bottom panel).

Fig. 2

First 24 hour heart rate variability (HRV) association with electroencephalogram (EEG), magnetic resonance imaging (MRI), and death in neonates with hypoxic ischemic encephalopathy (HIE). Mean HRV (standard deviation of inter-heartbeat intervals) for each patient in the first 24 hours after birth is shown based on findings on (A) early EEG (first 24 hour), (B) brain MRI, and (C) survival. In each panel, filled symbols represent better outcomes and open symbols worse outcomes. Horizontal bars indicate the mean for the group. Nml, normal; Mod/sev, moderate/severe. *p = 0.02, **p = 0.01, ***p < 0.001.

Fig. 3

Mean daily heart rate variability (HRV) and heart rate characteristics (HRC) index based on electroencephalogram (EEG) findings. The HRC index incorporates and is inversely correlated with HRV. Mean and standard deviation for daily (A) HRC index and (B) HRV are shown for infants with normal/mild encephalopathy on early (< 24 h) EEG compared with those with moderate-to-severe encephalopathy on early EEG. *indicates a p value < 0.05.