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Febrile infants (younger than 90 days of age): Outpatient evaluation

Authors:

Hannah F Smitherman, MD

Charles G Macias, MD, MPH

Section Editors:

Stephen J Teach, MD, MPH

Sheldon L Kaplan, MD

Deputy Editor:

James F Wiley, II, MD, MPH

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Sep 2016. | This topic last updated: Sep 06, 2016.

INTRODUCTION — The outpatient evaluation of febrile infants younger than 90 days of age is discussed in this topic.

For a discussion of the management of febrile infants younger than 90 days of age; definition of fever in the young infant; the diagnosis, evaluation, and initial management of early-onset sepsis in neonates; and the approach to the ill-appearing infant without fever, refer to the following topics:

●(See "Febrile infant (younger than 90 days of age): Management".)

●(See "Febrile young infants (younger than 90 days of age): Definition of fever".)

●(See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm infants", section on 'Evaluation and initial management'.)

●(See "Approach to the ill-appearing infant (younger than 90 days of age)".)

DEFINITION OF FEVER — Rectal temperatures are the standard for detecting fever in infants less than 3 months of age; the majority of studies establishing the risk of serious infections in febrile young infants have relied upon rectal temperatures. We regard a rectal temperature of 38°C (100.4°F) or greater as fever in infants 90 days of age and younger. (See "Febrile young infants (younger than 90 days of age): Definition of fever", section on 'Definition of fever'.)

Interpretation of other means of temperature measurement and caregiver reports of fever in young infants are discussed in detail separately. (See "Febrile young infants (younger than 90 days of age): Definition of fever", section on 'Definition of fever'.)

ETIOLOGY — The ability to generalize data from prior studies of the infectious etiology of fever in young infants is limited because many studies were conducted in an era when numerous vaccines that are now included in routine childhood immunizations were unavailable (eg, pneumococcal conjugate vaccine,Haemophilus influenzae type b vaccine, varicella vaccine, and rotavirus vaccine) and perinatal prophylaxis for group B Streptococcus was less common. Additionally, the Advisory Committee on Immunization Practices recommends influenza vaccine administration for all children ≥6 months [1]. While vaccination for influenza does not directly impact the youngest infants, older children serve as the most effective vectors of disease transmission in the community. Consequently, the epidemiology of influenza in the youngest infants is likely affected by the vaccination of older children and adult family members.

Viral infection — Viral infection is the most common cause of fever in young infants. In a study of infants 28 days or younger, including a subgroup of 960 neonates with fever, 17 percent had identifiable viral infections and 14 percent had an invasive bacterial infection [2]. By contrast, a prospective study of 1779 febrile infants 1 to 90 days of life identified viral pathogens in 35 percent of the cohort versus bacterial pathogens in 10 percent [3].

The neonate acquires infection through vertical transmission from the mother during delivery and postnatally from sources such as family members and hospital personnel. Neonates and young infants are more likely than older infants to experience morbidity from a viral infection, in part because of a decreased responsiveness of T cell-mediated immunity. (See "Immunity of the newborn".)

Viruses that can cause serious illness in febrile young infants include:

●Herpes simplex virus (see "Neonatal herpes simplex virus infection: Clinical features and diagnosis")

●Varicella-zoster virus (see "Varicella-zoster infection in the newborn")

●Enteroviruses (see "Clinical manifestations and diagnosis of enterovirus and parechovirus infections")

●Influenza virus (see "Seasonal influenza in children: Clinical features and diagnosis", section on 'Clinical features')

●Some adenoviruses (see "Epidemiology and clinical manifestations of adenovirus infection")

●Respiratory syncytial virus (see "Respiratory syncytial virus infection: Clinical features and diagnosis")

Invasive bacterial infection (IBI)

Definition — Many of the studies of fever in the young infant defined outcomes by the occurrence of serious bacterial infection (SBI) defined as invasive infections such as bacteremia, bacterial meningitis, bacterial pneumonia, skin and soft tissue infections, osteomyelitis, bacterial gastroenteritis, septic arthritis, or urinary tract infection (UTI) [4]. Although not classically described in the literature of the early 1990s, the attention to community-acquired Staphylococcus aureus has made pustulosis a relevant disease entity to be considered in skin and soft tissue infections in neonates [5].

More recently, the focus on the specific type infection (eg, UTI, bacteremia, or meningitis) has replaced the general concept of SBI in terms of evaluation and management secondary to the overall decreased prevalence of bacterial infections in the febrile infant and the unique nature of risk attributed to the specific type of infection. IBI, which refers to bacteremia and meningitis, has become the more common term. (See "Febrile infant (younger than 90 days of age): Management", section on 'Management'.)

Risk factors — Risk factors for IBI in young infants include the following [4,6-10]:

●Age, especially younger than 28 days – Observational studies performed after the introduction of vaccination against Haemophilus influenzae type b and evaluating febrile neonates 28 days of age and younger who presented to an emergency department have reported a higher prevalence of IBI (9 to 19 percent) [4,6,11-13] compared with approximately 7 to 11 percent in infants 29 to 90 days of age [6,13]. Similarly, febrile neonates evaluated in primary care physician offices have a higher rate of bacteremia and meningitis than older febrile young infants as follows [7]:

•3 and 1.1 percent, respectively, in infants 0 to 1 month of age

•1.4 and 0.4 percent, respectively, in infants from 0 to 2 months of age

•0.7 and 0 percent, respectively, in infants from 2 to 3 months of age

●Ill-appearance – Ill-appearance has consistently been associated with a higher risk of IBI based upon clinical experience and multiple observational studies [7,8,14]. However, a substantial number of previously healthy, well-appearing infants without a focus of infection on physical examination can also have an IBI.

●Rectal temperature ≥40°C (104°F) – Hyperpyrexia is rare among febrile infants younger than 3 months but is highly associated with IBI when it occurs. As an example, in an observational study of 98 infants younger than 90 days of age, patients with a temperature ≥40°C had a 29 percent absolute increase in the frequency of SBI (38 versus 9 percent) [10].

●Rectal temperature ≥38.6°C (101.5°F) – The risk for bacterial etiology appears to increase with increasing fever (historically defined in the literature for infants of >38.0°C or >38.5°C) despite a decrease in the incidence of invasive disease across all ages following the introduction of conjugate vaccines. (See'Etiology' above.)

Although increasing temperatures may increase risk, thresholds merely represent cutoffs described in the literature for the purposes of research; true risk is a continuum. Nevertheless, many experts use fever ≥38.6°C (101.5°F) as an additional risk factor that requires a full sepsis evaluation.

●Unimmunized (have not received the first dose of pneumococcal and Hib vaccine) – Immunization with conjugate pneumococcal vaccines has significantly decreased the rates of bacteremia in young infants and children and, in young infants, it appears to both confer direct and herd immunity benefits [9]. As an example, in an observational cohort study that identified children 3 years of age or younger and included 50 immunized and 67 unimmunized infants 0 to 90 days of age, the rates of bacterial infection were significantly higher among unimmunized febrile young infants 0 to 90 days of age (7 percent unimmunized versus 0 percent, respectively). In addition, there were no cases of pneumococcal bacteremia in any of the infants who had received at least one dose of heptavalent pneumococcal vaccine or the 22 unimmunized infants younger than 28 days.

●Prematurity (gestational age younger than 37 weeks) – Because of their immature immune protective mechanisms, premature infants are at a much higher risk for IBI. For example, premature infants have rates of sepsis that are approximately 10 to 12 times that of term infants, including late-onset sepsis. Thus, febrile young infants who are premature should be regarded as being at an increased risk for invasive bacterial infection. (See "Clinical features and diagnosis of bacterial sepsis in the preterm infant ( ................
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