Introduction

It is very important for newborns till the age of a year and a half to look for any health-related complications due to their developing immunity. Especially fever should be taken very seriously as it could be a sign of fatal infection. Bacterias like Streptococcus pneumoniae and Haemophilus influenzae are the most common bacteria that can cause infection in newborns of zero to three months of age. But the worldwide use of numerous vaccinations has significantly decreased the rate of this bacterial infection as compared to the past.

If a child is showing persistent signs of fever, it is required to go with extensive diagnostic measures, but procedures like lumbar puncture and chest radiography are now not recommended if there is no other complication related to fever. If the child is less than 90 days of age and the rectal temperature is greater than 38.0 Celsius, the diagnosis is fever with possible complications owing to an immature immune system. Febrile infants are more susceptible to bacterial infections like urinary tract infection (UTI), bacteremia, and meningitis.

Because of age, it is easy to not recognize any health-related issue without symptoms in infants. However, if the caregivers keep a regular check and note the temperature (ear, rectal, or axillary) and physical appearance, it can be easier to diagnose the complication at an early stage. Moreover, even if the infant is well-appeared without any signs, there are a few signs like irregular bowel movement or loss of appetite and sleep that show the health-related issues.

What Are the Differential Diagnosis of Fever in Infants?

As discussed earlier, febrile infants should be evaluated for urinary tract infection or meningitis and viral infections, as they are quite common in this age group. Some differential diagnoses according to symptoms are,

• Well-Appearing Febrile Infants:

  • Bacterial Infections -

    • Bacteremia: When there are various bacterias like Streptococcus pneumoniae or Salmonella that cause the infection.

    • Meningitis: It is inflammation of the membrane around the brain caused by a viral infection, bacterial infection, or sometimes fungal infection.

    • Pneumonia: Viruses like a respiratory syncytial virus, SARS-CoV-2, or bacterias like Streptococcus pneumoniae cause the infection in the lungs. Due to the infection, the air sac will be infected and filled with pus, causing an inflammatory reaction in the lungs.

    • Bone Joint Infections: Some bacteria-caused bone joint infections can be spread through open and infected wounds through muscle and bloodstream to bones, such as osteomyelitis.

    • Soft Tissue Infection: When due to bacterial invasion, the infection spreads to the skin and soft tissue, such as necrotizing fasciitis.

    • Urinary Tract Infections: Due to the body’s immunity failure, sometimes bacteria like Escherichia coli enter the urinary tract via the urethra and colonize there, causing infection.

  • Viral Infections -

    • Enterovirus: It is a single-stranded RNA (ribonucleic acid) virus that usually affects infants causing fever, rash, or runny nose.

    • Bronchitis: When bronchial tubes carrying air from the lungs are inflamed due to a viral infection, it causes shortness of breath, fatigue, fever, and chest discomfort.

    • Neonatal Herpes Simplex: It is a transmitted viral infection during the time of birth.

• Ill-Appearing Febrile Infants:

  • Infectious -

    • Serious Bacterial Infection: Infection that creates life-threatening situations in infants, such as sepsis, bacterial gastroenteritis, or ethmoiditis.

    • Enterovirus: Same as discussed above, it is a single-stranded RNA virus especially affecting infants.

    • Respiratory Syncytial Virus: It is a very common respiratory virus that causes runny noses and congestion in infants.

  • Metabolic -

    • Congenital Adrenal Hyperplasia: When a group of disorders created by a lack of enzyme secretion in the body affects the adrenal glands.

    • Inborn Errors of Metabolism: It is a rare genetic disorder where the body is unable to digest food due to a lack of enzymes that help in metabolism.

  • Cardiac -

    • Ductal Dependent Left and Right-Sided Obstructive Lesions: Due to severely hypoplastic right or left ventricle, the systemic pulmonary circulation is compromised, causing difficulty in transition from prenatal to postnatal circulation after birth.

What Are the Signs of Fever in Infants?

There are many signs and symptoms associated with different areas of a child’s health:

• Daily Activity -

  • Weakness.

  • Loss of sleep.

  • Continuous crying.

  • Cranky.

  • Lethargy.

  • Drowsiness.

• Skin and Color Changes -

  • Pale skin.

  • Cyanosis.

  • Rashes.

  • Decrease skin elasticity.

  • Crackles.

• Respiration -

  • Tachycardia (when the heart rate is over 100 beats per minute, it causes conditions like hypertension).

  • Hypoxia (when the oxygen level in tissues drops, it is called hypoxia.)

  • Apnea (when the brain does not send prompt signals to muscles to control breathing, it causes an abrupt stop and start of breathing rhythm).

  • Grunting.

  • Shortness of breathing.

  • Hypotension.

• Hydration and Circulation -

  • Dry mucous membrane.

  • Loss of appetite.

  • Poor peripheral circulation.

  • Reduced urine output.

• Neurological -

  • Neck stiffness.

  • Seizures.

  • Bulging fontanelle (it is a sign of brain swelling).

  • Unconsciousness.

What Are the Diagnostic Measures of Fever in Infants?

Even though the physical examination is the first step in diagnosing the disease, the persistent fever shows that there are other complications associated with it in infants. Therefore some other diagnostic measures should be done to identify the cause, such as:

• Blood Culture - If the normal count of white blood cells and neutrophils is disturbed, it identifies the infection in the body. The current guidelines suggest that for febrile infants younger than three months, a blood count with differential and blood culture is required.

• Urinalysis and Urine Culture - As urinary tract infection is commonly seen in younger children, urinalysis plays a very important role in diagnosing the infection. It often seems to be very difficult to obtain urine samples in younger children, but young ones less than 24 months of age are required to give specimens for testing via catheterization or suprapubic aspiration. For older children, the clean catch method works very well. Also, urinary tract infection rate varies according to age and gender; for the first three months after birth, it is more common in boys than girls, and after three months of age, it is more common in girls than boys.

• Stool Testing - In the cases where fever is persistent with other symptoms like diarrhea, the stool test is done to count fecal WBC (white blood cells) count.

• Inflammatory Markers - In case of infection, C-reactive protein (CRP) is produced in the liver as a result. It is also known as inflammatory markers because it is the result of inflammation of organs caused by infection and other tissue injuries. Prolactine, another marker, is also known to be sensitive to inflammation caused by bacterial infection.

• Lumbar Puncture - This test is specifically recommended for febrile infants with the signs of meningitis. Although due to vaccination for S. pneumoniae and Haemophilus influenzae type b, the chances of having this infection have reduced to a great extent. When the peripheral WBC count is less than 5,000 per mm3, the blood count should not be trusted alone for the diagnosis.

• Imaging - When a more than a month old child shows any respiratory distress along with a fever of more than 102 Celsius, it is best to go for a chest radiograph.

• Viral Testing - The virus such as Herpes simplex is very uncommon in infants. It carries fatal risk factors like seizures and cerebrospinal fluid pleocytosis. If the viral infection is detected, it can be managed by intravenous Acyclovir medication.

• Rapid Viral Testing - These days, rapid testing is available for viruses such as Influenza and others. It is very unlikely for children with a viral infection to have bacterial infections. However, in some cases, urinary tract infection is seen with the respiratory syncytial virus.

How to Manage Fever in Infants?

• The Treatment Plan for Infants Younger Than 29 Days:

  • Check for the physical signs and symptoms.

  • Check for the temperature if it is greater than 38.0 Celsius.

  • Obtain urinalysis, blood culture, lumbar puncture samples, obtain inflammatory markers, stool culture, and fecal WBC count if there is persistent diarrhea.

  • If any of the diagnostic methods suggest the infection of the herpes simplex virus, send other samples for the HSV study.

  • Start with empiric antibiotics after the culture has been received and there is a positive infection found.

    • Ampicillin 100 to 200 mg/kg/day in intravenous or intramuscular administration.

    • Gentamicin 2.5 mg/kg/day every eight hours, intravenous or intramuscular administration.

• The Treatment Plan for Infants Older Than 29 Days:

  • In infants older than one month, look for persistent signs, such as cyanosis, poor peripheral circulation, neurological changes, and meningeal irritation.

  • According to age, the CBC (complete blood count) with differential and blood culture, urinalysis, lumbar puncture, stool test, and chest radiography are suggested for infants.

  • Age-appropriate antibiotic therapy is prescribed.

• Infants Older Than One Month With Urine Findings -
• Cefotaxime, 50 mg/kg, intravenous administration every eight hours.
• Alternatively, Cefixime, 8 mg/kg twice on the first day, then once daily.

• One to Three Months, When Meningitis Is Not Suspected -

  • Ceftriaxone, 50 mg/kg/day, intravenous or intramuscular administration every 12 to 24 hours.

• One to Three Months, When Meningitis Is Concerned -

  • Ceftriaxone, 100 mg/kg/day, intravenous or intramuscular administration every 12 to 24 hours.

• One to Three Months, Listeria or Enterococcus Is a Concern -

  • With the other antibiotics, add Ampicillin 100 to 200 mg/kg/day intravenously or intramuscularly for every six hours.

• Infants Older Than Three Months, Suspected of Pneumonia -

  • Amoxicillin 80 mg/kg/day divided into eight to twelve hours.

  • Alternatively, Azithromycin 10 mg/kg orally on day 1, then 5 mg/kg daily for the next four days.

• If the symptoms are not cured by any of the antibiotics, the infant should be admitted to the hospital for close monitoring and treatment.

Conclusion

Until the age of 36 months, newborns are at great risk of developing an infection caused by viruses, parasites, or bacteria. After the treatment, the caregivers should keep an eye on recurring symptoms and vitals. Also, a follow-up visit to the doctor is as important as the treatment and diagnosis. Fever in infants can have many etiological factors, and if the signs and symptoms are not resolved with antibiotics treatment, it is wise to hospitalize them immediately.