Heart Rate Variability in Febrile Young Infants (HRV)

Rapid Triage for Serious Infections in Infants Younger Than 3 Months Using A Novel Heart Rate Variability Tool

Febrile infants younger than 3 months old present a diagnostic dilemma to the emergency physician. Tension remains between the need for early aggressive intervention among patients with suspected sepsis and the global phenomena of increasing antibiotic resistance.

The investigators aim to: (1) To study the association between heart rate variability (HRV) and the presence of a serious infection (SI) among infants younger than 3 months old. The investigators hypothesize that a reduced HRV is associated with the presence of SI. (2) To compare HRV between febrile infants < 3 months with non-febrile infants. The investigators hypothesize that the variability will be reduced in febrile infants with SIs when compared to non-febrile well infants, but not among febrile infants without SIs when compared to non-febrile well infants. (3) To study if HRV will provide incremental diagnostic information over current triage tools.

Study Overview

• Status: Completed
• Conditions: Triage; Heart Rate; Decision Support Techniques; Variability
• Intervention / Treatment: Device: Single lead ECG

Detailed Description

Febrile young infants younger than 3 months old present a diagnostic dilemma to the pediatric emergency department (ED) physician. The potential for a missed serious infection (SI) poses the threat of premature death and long-term disability among these infants. Despite decreasing early-onset neonatal sepsis rates due to obstetric prevention strategies, high rates of hospitalization and administration of parenteral antibiotics occur in this age group. Continual tension remains between the need for early and aggressive intervention among patients suspected with sepsis and the global phenomena of increasing antibiotic resistance. Research networks have attempted to build diagnostic algorithms to guide the identification of these ill infants. These are often useful as adjuncts to the clinician's gestalt, but generalizability remains questionable.

Vital signs are of paramount importance in recognizing ill children and have been used in pediatric early warning system scores (PEWS) and various triage systems. Vital signs have resurfaced as the focus of research in recent years, with various groups purposing to update evidence-based normal heart rate ranges among children. Normative heart rate ranges are infamously difficult to define due to the hemodynamic lability in these young infants, multiple confounders for abnormal heart rate, and the variable physiological response during acute stress states.

Previous pilot data showed that the Advanced Paediatric Life Support (APLS) and Fleming (<10th or >90th centile) guidelines performed with the highest sensitivity (66.0% and 62.6%, respectively) and the highest Negative Predictive Value (NPV) (73.3% and 71.4%, respectively). No single guideline reached a sensitivity of greater than 70%.

Objectives and Hypothesis

1. To study the association between heart rate variability (HRV) and the presence of a serious infection (SI) among infants younger than 3 months old. The investigators hypothesize that a reduced HRV is associated with the presence of SI.
2. To compare HRV between febrile infants < 3 months with non-febrile infants. The investigators hypothesize that the variability will be reduced in febrile infants with SIs when compared to non-febrile well infants, but not among febrile infants without SIs when compared to non-febrile well infants.
3. To study if HRV will provide incremental diagnostic information over current triage tools.

• Study Type: Observational
• Enrollment (Actual): 330

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 229899
    • KK Women's and Children' Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 3 months (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

330 infants < 3 months presenting with fever. Fever is defined as an axillary or rectal temperature ≥ 38oC.

75 infants < 3 months (clinically well) presenting without fever. These include young infants presenting for neonatal jaundice or other non-febrile conditions.

Description

Inclusion Criteria:

• Infants < 3 months presenting to the ED will be included (both febrile and non-febrile) Febrile infants are those with an axillary or rectal temperature ≥ 38oC at triage and/or outside of the hospital. OR Non-febrile infants include those presenting to the ED for serum bilirubin checks or otherwise

Exclusion Criteria:

• Infants who are in active resuscitation for septic shock. Infants of parents who refused to give informed consent. Premature infants delivered at a gestation of < 35 weeks.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Febrile infants; Febrile Infants less than 3 months presenting to the emergency department with a temperature of ≥ 38oC.	Device: Single lead ECG; Heart Rate Variability will be monitored using a single lead electrocardiogram
Afebrile infants; Afebrile Infants less than 3 months presenting to the emergency department	Device: Single lead ECG; Heart Rate Variability will be monitored using a single lead electrocardiogram

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with Serious Infections	Serious infections are defined by: Sepsis, meningitis, lobar pneumonia, osteomyelitis, abscess, and urinary tract infection	Within 2 weeks of hospitalisation

Collaborators and Investigators

• Sponsor: KK Women's and Children's Hospital
• Collaborators: National Medical Research Council (NMRC), Singapore

Publications and helpful links

General Publications

• Chong SL, Ong GY, Allen JC, Lee JH, Piragasam R, Koh GZX, Mahajan P, Liu N, Ong MEH. Early prediction of serious infections in febrile infants incorporating heart rate variability in an emergency department: a pilot study. Emerg Med J. 2021 Aug;38(8):607-612. doi: 10.1136/emermed-2020-210675. Epub 2021 Apr 16.

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2017
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: September 8, 2019
• First Submitted That Met QC Criteria: September 23, 2019
• First Posted (Actual): September 25, 2019

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: HRV-INFANTS-2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will be shared with current study team. Sharing of de-identified data with collaborators will be reviewed by the study team.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No