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.

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.

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.

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.

Individual participant data will be shared with current study team. Sharing of de-identified data with collaborators will be reviewed by the study team.