Practice Essentials
Fever is an abnormal elevation in body temperature (≥38.0°C or 100°F) and is a sign of infection. It is one of the most common problems in infants and toddlers.
Fever may indicate a mild, self-limiting viral infection or a severe, life-threatening bacterial infection. Serious bacterial infection (SBI) implies bacteremia, bacterial meningitis, and bacterial urinary tract infection. An invasive bacterial infection (IBI) implies bacteremia and bacterial meningitis. The prognosis depends upon the cause and severity of the infection. Fever in infants and toddlers poses a challenge for pediatricians and often requires a workup, especially in situations of a fever without any other focus of infection.
This article addresses the most common etiologies of fever in these age groups and the appropriate clinical prediction rules for identifying infants and toddlers at the lowest risk for SBIs. Recommendations from the latest clinical practice guidelines on the evaluation of well-appearing febrile infants 8-60 days of age are included. (See also Fever Without a Focus and Emergent Management of Pediatric Patients With Fever.)
Background
The infectious causes of fever depend on age, immune system maturity, and exposure. This article categorizes the cause of fever, its workup, and management into age groups: neonates 0 to 21 days, neonates 22 to 28 days, young infants 29 to 90 days, and infants and children 3 months to 3 years.
A fever of concern generally is defined by a temperature ≥38.0°C (100.4°F). Regarding the site for temperature measurement, the Bright Futures Guidelines for health supervision suggest rectal thermometer use for patients younger than 4 years of age. The National Institutes of Health recommends axillary measurement for neonates less than 4 weeks old and axillary or tympanic for infants and children from 4 weeks to 5 years of age. The axillary thermometer is easy to use, more acceptable to parents, and provides quicker results in neonates younger than 4 weeks. Similarly, an axillary or infrared tympanic membrane thermometer conveniently provides temperature measurement in infants older than 4 weeks and children younger than 5 years of age.
Neonates
Neonates (aged ≤28 days) with fever may have few clues on history taking and physical examination. Therefore, the decision to conduct a workup and the extent of the investigation are primarily based on the risk of infection determined by neontal age and prenatal testing results.
The risk of invasive bacterial infection (IBI) such as bacteremia and bacterial meningtis is age dependent. The risk of IBI is highest in febrile neonates aged < 21 days: it is estimated at 3-5% for bacteremia and 1.1-2.7% for meningitis. [1] The risk of IBI in neonates aged 22-28 days is relatively lower at 0.2-0.7%. [2, 3] Typically, infections that occur in the first 7 days of life are secondary to vertical transmission, and those infections occurring after the first 7 days are usually community acquired or hospital acquired.
Obtaining the pertinent medical history regarding the pregnancy, delivery, and early neonatal life of the febrile neonate is essential. Note the following:
-
A pediatrician should review prenatal laboratory results for infections such as human immunodeficiency virus (HIV), syphilis, and hepatitis C
-
Maternal immunity for rubella and varicella should be checked
-
Maternal group B Streptococcus (GBS) colonization status should be ascertained, and if positive, whether the mother was treated adequately at least 4 hours before delivery
-
A review of testing for acute cytomegalovirus (CMV) infection and toxoplasmosis during pregnancy should be conducted
-
In a mother with suspected genital primary herpes simplex virus (HSV) infection during labor and delivery, the pediatrician should review testing for maternal HSV polymerase chain reaction (PCR) from genital lesions and maternal immunity to herpes simplex
-
A history of maternal febrile illness before delivery in the summer months may indicate an enteroviral infection; a history of maternal flu-like illness before delivery during winter may be a clue to maternal SARS-CoV-2 infection or influenza
-
A history of a vesicular rash near delivery requires investigation for maternal varicella-zoster virus infection (primary varicella and zoster)
Definitive identification of a serious bacterial infection requires laboratory investigation; a full sepsis evaluation; and a positive result in blood culture, cerebrospinal fluid (CSF), and/or urine. Bacterial meningitis is more common in the first month of life than at any other time. An estimated 5-10% of neonates with early-onset GBS sepsis have concurrent meningitis. [4] The incidence of Staphylococcus aureus bacteremia in infants aged < 1 year has consistently been higher than in older children. The incidence in infants has been reported as high as 16.7 per 100,000 population and in neonates as high as 124.8 per 100,000. [5, 6]
Young Infants
The general approach to fever in a febrile infant aged 29-60 days includes maintaining a high index of suspicion because they often lack clues on physical examination. The prevalence of a serious bacterial infection in infants younger than 3 months is approximately 6-10%, most often urinary tract infections (UTIs). Interestingly, infants aged 3 months or younger with a confirmed viral infection are at lower risk for a serious bacterial infection when compared with those in whom a viral infection is not identified [7] ; however, a UTI is still a significant concurrent infection (3.3%) in infants with bronchiolitis. [8]
According to guidelines from the Agency of Health Care Policy and Research published in 2012, in infants younger than 3 months with rectal temperatures 38ºC (100.4°F) or higher, the prevalence of serious bacterial infection reported in studies conducted in North American emergency departments or primary care practices ranged from 4.1% to 25.1%. [9, 10]
Children Aged 3 Months to 3 Years
Historically, children aged 3 months to 3 years with rectal temperatures of 38.5ºC (101.3ºF) or higher had a risk of 2-4% for occult bacteremia. [11] The leading cause of bloodstream infection was Streptococcus pneumoniae, followed by Haemophilus influenzae type b. With the introduction of effective vaccines for these pathogens, the incidence and epidemiology of childhood bacteremia in the immunologically normal host has changed considerably; only 1 in 200 (0.5%) febrile children are now found to be bacteremic. [12, 13]
The incidence of occult bacteremia in this population now ranges from 0.25% to 0.7%; moreover, 2 of every 3 blood isolates from these children represent a contamination and not a true pathogen. [12, 14, 15]
S pneumoniae and Escherichia coli are the most common pathogens, accounting for two thirds of cases. Invasive pneumococcal disease is most common in children younger than 5 years. In infants with S pneumoniae, many isolates are strains not covered by the currently available 15- and 20-valent pneumococcal conjugate vaccines. Children with pneumococcal bacteremia may present with a focus, such as acute otitis media, pneumonia, symptoms of sinusitis, meningitis, or cellulitis (including orbital or facial cellulitis), or nonspecific febrile illnesses without a focus. E coli bacteremia is most common in children aged younger than 1 year and is usually associated with a UTI. Staphylococcus aureus may be associated with skin, soft tissues, or musculoskeletal infections. Salmonella species, Neisseria meningitidis, and Streptococcus pyogenes account for most of the remaining infections. After the COVID-19 pandemic, invasive group A streptococcal infections increased in children in the United States and in several European countries. [16, 17]
The approach to the febrile child aged 3 months to 3 years consists of a targeted medical history, a complete physical examination, and the judicious use of the laboratory tests.
Pathophysiology
Fever is a centrally mediated rise of body temperature higher than the normal daily variation in response to a stimulus such as a pathogen. Tissue damage and pathogens result in the release of cytokines (interleukin-1 [IL-1], IL-6, tumor necrosis factor, and interferon alpha) by the reticuloendothelial system, macrophages, and endothelium. These cytokines reach the optic area of the hypothalamus via systemic circulation and release primarily prostaglandin E2 (PGE2) by the hypothalamic endothelium. PGE2 raises the temperature set point to an elevated temperature, resulting in increased metabolic rate and decreased heat loss from the body. [18]
Patient Education
A study estimated the extent to which Canadian expectant parents would seek medical care in a febrile neonate (aged 30 days or younger). The study also evaluated expectant parents' knowledge of signs and symptoms of fever in a neonate and the actions Canadian expectant parents would take to optimize the health of their child. Despite universal access to high quality health care in Canada, the study highlighted concerning gaps in the knowledge of the care of the febrile infant in one fifth of expectant parents. Physicians and health providers should strive to provide early education to expectant parents about how to recognize signs of fever in the neonate and how best to seek medical care. [19]
Tables
What would you like to print?
- Valley Fever Risk Remains High in California This Fall
- Maternal Obesity Linked to Sudden Infant Death
- Nirsevimab Cuts Hospitalisation Risk in Infant Bronchiolitis
-
CDC Warns About Potentially Deadly Virus in Infants
-
Pediatric Asthma: When Is It an Emergency?
- Clinical and Biochemical Characteristics of Untreated Adult Patients With Resistance to Thyroid Hormone Alpha
