74 - Decreased Heart Rate Variability and Elevated Inflammatory Cytokines in Preterm Neonates with Late Onset Infection

Poster Number: 74

Dosalyn R. Thompson, Penn State Children's Hospital, Hershey, PA, United States; Jaimie E. Wardinger, Penn State Children's Hospital, Harrisburg, PA, United States; Fumiyuki C. Gardner, Pennsylvania State University College of Medicine, New Cumberland, PA, United States; Brittany J. Fronheiser, Pennsylvania State University College of Medicine, Camp Hill, PA, United States; Liz M. Sanchez Pena, Penn State College of Medicine, Lebanon, PA, United States; Kim K. Doheny, Penn State College of Medicine and Penn State Children's Hospital, Hershey, PA, United States

Background: Late onset infection contributes to significant morbidity and mortality for preterm infants. Heart rate variability (HRV) which reflects counterbalancing of parasympathetic and sympathetic inputs shown in beat-to-beat interval variance has been demonstrated as a useful index for predicting neonatal morbidity. However, less is known on the predictive utility of HRV in inflammatory mediated pathways.

Objective: We aimed to test that diminished parasympathetic tone measured by the high frequency (HF) component of HRV (HF-HRV) and elevated levels of inflammatory cytokines would have utility in predicting neonatal late onset infection.

Design/Methods: In this multi-site prospective cohort/comparison study, we enrolled 250 preterm (26-34 weeks’ PMA) neonates. Post-prandial ECG was obtained in the afternoon on day 5-8 of life and weekly thereafter until 35weeks’ PMA and processed using frequency domain analysis. Blood cytokines were measured at 1 and 3 weeks of life and at the time of sepsis work-up. The electronic medical record was used to calculate the score for neonatal acute physiology (SNAP), and to confirm evidence of late onset infection defined as neonatal infection that occurred after day 7 of life. Neonates with positive meconium toxicology for opioids (n=2) were excluded as they are known to have autonomic dysregulation. In addition, neonates with gastrointestinal pathology (n=32) were excluded from this analysis as those results have been reported previously.

Results: HF-HRV was decreased at weeks 1 and 2 of life in neonates who developed late onset infection (n=10) vs controls (n=206) at p=.01 for both. There were no differences in mean cytokine levels between cases and controls. However, Low HF-HRV was associated with elevated TNF-α (p=.03) and IL-8 (p=.01) at week one of life. Logistic regression with SNAP and HF-HRV as predictors indicated that only HF-HRV at day 5-8 days of life was a significant predictor of late onset infection with an odds ratio of 0.43; 95% CI: 0.21-0.88; p=.02.Conclusion(s): The association of low HF-HRV with elevated inflammatory cytokines in evolving infection provides evidence for the putative role of the vagal cholinergic pathway in sepsis pathogenesis. HRV is a useful modality for identification of those neonates at risk for late-onset infection.

Funding: NIH-DK09935, Pediatric Departmental Funding
Dosalyn Thompson's CVCV updated 1.7.22.pdf