Neonatal sepsis is a major cause of hospitalization and infant death and can result from meningitis, pneumonia, gastroenteritis, or other serious infections. Early detection and treatment can reduce morbidity and mortality, but nonspecific symptoms cause difficulty in differentiating bacterial and viral infections. Recently, the Surviving Sepsis Campaign (SSC) released an international guideline for the management of septic shock and sepsis-associated organ dysfunction in children, which serves as a companion to the SSC guideline for adult sepsis. Although there are no definitive confirmatory diagnostic tests for sepsis, laboratory tests including blood cultures, C-reactive protein (CRP), and procalcitonin (PCT) tests can contribute to the investigation of sepsis and help in determining when to discontinue treatment.
Quick Answers for Clinicians
Most infants with early-onset sepsis will exhibit abnormal signs in the first 24 hours after birth, although any critically ill infant should be immediately evaluated for sepsis and receive empirical broad-spectrum antimicrobial therapy after cultures, even if obvious risk factors for sepsis are absent.
There is no definitive diagnostic test for sepsis. Along with clinical data, laboratory testing can provide clues that indicate the presence of or risk of developing sepsis. Blood culture is useful to investigate the severity of sepsis and to monitor therapeutic response and should be performed before antimicrobial therapy if testing will not delay antimicrobial administration. If blood cultures cause a delay, antimicrobial treatment should take precedence. The American Academy of Pediatrics (AAP) recommends that all newborn infants with suspected sepsis have a lumbar puncture if stable enough for the procedure. Other tests, including CBC and chemistries, provide baseline data to assess therapeutic response.
Procalcitonin (PCT) is a proposed marker for early sepsis in infants and is more sensitive than C-reactive protein (CRP), but less specific; in addition, the interpretive cutoffs established for adults may not be transferable to the pediatric population. CRP results are helpful to rule out neonatal sepsis in full-term infants; a cutoff of 2.0-2.5 ng/mL is moderately accurate in predicting neonatal sepsis. Recent studies suggest similar efficacy in preterm infants.
Indications for Testing
Most cases of neonatal sepsis (roughly 80-90%) present in the first 2 days of life. Manifestations range from nonspecific symptoms to multiorgan failure. Infants rarely present with fever unless born to a febrile mother, although some acquire fever immediately after delivery. It is more common for an infant to be hypothermic or to present with pneumonia, two nonspecific signs of sepsis. Other presenting signs that warrant investigation include lethargy, irritability, poor feeding, respiratory symptoms (eg, apnea, grunting), and abdominal distention.
Neonatal sepsis is defined as a systemic infection occurring in infants ≤28 days old. Early-onset neonatal sepsis is defined as sepsis presenting within 72 hours of birth, and late-onset sepsis as sepsis occurring after 72 hours in infants in the neonatal intensive care unit (NICU) and after 7 days of life in full-term infants.
Initial Workup of Suspected Neonatal Sepsis
Initial, nonspecific testing (eg, urine cultures, white blood cell [WBC] counts) may prove useful for identifying infants with a low probability of developing sepsis, but not for identifying infants likely to be infected.
A single blood culture is used to determine the presence of bacterial infection. The culture should be obtained before beginning antimicrobial therapy, unless doing so will substantially delay antimicrobial administration.
Cerebrospinal Fluid Studies
Cerebrospinal fluid (CSF) studies provide optimal diagnostic sensitivity for detecting sepsis. The American Academy of Pediatrics (AAP) recommends that all newborn infants with suspected sepsis have a lumbar puncture if stable enough for the procedure. CSF studies are not necessary in all infants with suspected sepsis; if there are no obvious maternal risk factors or there is suspicion that a noninfectious etiology may be involved, CSF studies can be deferred. However, if blood cultures are positive or infants fail to respond to therapy, a lumbar puncture should be obtained and tested.
CRP is a nonspecific marker of acute inflammation. Evidence supports the use of CRP to help rule out neonatal sepsis in full-term infants, and recent studies suggest similar efficacy in preterm infants. CRP increases within 6-8 hours of infection and peaks at 24 hours. The sensitivity of CRP is initially low, but this marker has increased sensitivity 6-12 hours after birth. Two normal readings provide strong evidence that bacterial sepsis is unlikely and that any antibiotic treatment can be discontinued. There is no evidence to support repetition of CRP testing to determine duration of treatment in an infant with an increased CRP result (≥1.0 mg/dL).
PCT is another acute phase reactant that is used as a marker for the early detection of sepsis, and although it is more sensitive than CRP for identifying early sepsis, it is less specific. A physiologic increase in PCT occurs within the first 24 hours after birth and may arise in the presence of noninfectious conditions (eg, respiratory distress syndrome). The interpretive cutoffs established for adults may not be transferable to the pediatric population, but a cutoff of 2.0-2.5 ng/mL is moderately accurate in predicting neonatal sepsis.
The SSC recommends daily assessment for pediatric patients with septic shock or sepsis-associated organ dysfunction for the purpose of antimicrobial therapy de-escalation. This assessment may include microbiologic assessment, PCT measurement, or assessment of other indicators of infection resolution.
The SSC was unable to issue a strong recommendation about the utility of blood lactate values to stratify children with septic shock or other sepsis-associated organ dysfunction into risk categories for sepsis. However, trends in blood lactate concentrations are recommended to guide resuscitation of children with septic shock and other sepsis-associated organ dysfunction.
ARUP Laboratory Tests
Initial, nonspecific testing
Automated Cell Count/Differential
May be useful as a marker for early detection of sepsis
May aid in ruling out neonatal sepsis in full-term infants
May be used to identify pathogens before treatment
May be useful to evaluate suspected sepsis
Limited to the University of Utah Health Sciences Center only
Weiss SL, Peters MJ, Alhazzani W, et al. Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Intensive Care Med. 2020;46(Suppl 1):10-67.PubMed
Polin RA, Committee on Fetus and Newborn. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics. 2012;129(5):1006-1015.PubMed
Committee on Infectious Diseases, Committee on Fetus and Newborn, Baker CJ, et al. Policy statement--recommendations for the prevention of perinatal group B streptococcal (GBS) disease. Pediatrics. 2011;128(3):611-616.PubMed
Simonsen KA, Anderson-Berry AL, Delair SF, et al. Early-onset neonatal sepsis. Clin Microbiol Rev. 2014;27(1):21-47.PubMed
Pontrelli G, De Crescenzo F, Buzzetti R, et al. Accuracy of serum procalcitonin for the diagnosis of sepsis in neonates and children with systemic inflammatory syndrome: a meta-analysis. BMC Infect Dis. 2017;17(1):302.PubMed
Christensen RD, Yaish HM, Wiedmeier SE, et al. Neonatal death suspected to be from sepsis was found to be kernicterus with G6PD deficiency. Pediatrics. 2013;132(6):e1694-e1698.
Couturier BA, Weight T, Elmer H, et al. Antepartum screening for group B Streptococcus by three FDA-cleared molecular tests and effect of shortened enrichment culture on molecular detection rates. J Clin Microbiol. 2014;52(9):3429-3432.