Heart rate variability and inflammatory markers in neonates with hypoxic-ischemic encephalopathy.

To examine heart rate variability (HRV) and inflammatory markers as predictors for neurological injury in neonates undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE). We hypothesized that HRV would differentiate between infants with no/mild injury and infants with moderate/severe injury observed on MRI. Because HRV can be associated with the inflammatory cascade, cytokine concentrations were compared with the severity of brain injury indicated by MRI. Further, we studied the effect of temperature, sex, and mechanical ventilation on HRV. HRV was prospectively collected on neonates with HIE using spectral analysis for low and high frequency components (n = 16). A subset (n = 10) of neonates had serum available for inflammatory cytokine analysis obtained during cooling. Neonates were stratified into no/mild or moderate/severe injury based on MRI obtained after rewarming. Differences in HRV were identified; lower low frequency power predicted more injury on MRI. Additionally, in neonates with HIE after cooling procedure, HRV differed by gender. Elevated RANTES (CCL5) and decreased GM-CSF (Granulocyte-macrophage colony-stimulating factor) at 96 hours predicted less severe injury. In this small study, HRV differs between no/mild and moderate/severe injury in neonates with HIE. With further study, this may aid the clinician in real-time decision making. HRV differs by gender. Finally, inflammatory biomarkers may help elucidate the pathophysiology of HIE.

Enteral Feeding as an Adjunct to Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Withholding enteral feedings during hypothermia lacks supporting evidence. OBJECTIVES: We aimed to determine if minimal enteral nutrition (MEN) during hypothermia in patients with hypoxic-ischemic encephalopathy was associated with a reduced duration of parenteral nutrition, time to full oral feeds, and length of stay, but would not be associated with increased systemic inflammation or feeding complications. METHODS: We performed a pilot, retrospective, matched case-control study within the Florida Neonatal Neurologic Network from December 2012 to May 2016 of patients who received MEN during hypothermia (n = 17) versus those who were not fed (n = 17). Length of stay, feeding-related outcomes, and brain injury identified by MRI were compared. Serum inflammatory mediators were measured at 0-6, 24, and 96 h of life by multiplex assay. MRI were scored using the Barkovich system. RESULTS: MEN subjects had a reduced length of hospital stay (mean 15 ± 11 vs. 24 ± 19 days, p < 0.05), days receiving parenteral nutrition (7 ± 2 vs. 11 ± 6, p < 0.05), and time to full oral feeds (8 ± 5 vs. 18 ± 18, p < 0.05). MEN was associated with a significantly reduced serum IL-12p70 at 24 and 96 h (p < 0.05). Brain MRI scores were not significantly different between groups. CONCLUSION: MEN during hypothermia was associated with a reduced length of stay and time to full feeds, but did not increase feeding complications or systemic inflammation.