Neonatal Sepsis - Sepsis in Newborns

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. Although there are no definitive confirmatory diagnostic tests for sepsis, laboratory tests including blood cultures, C-reactive protein (CRP), and procalcitonin (PCT) can contribute to the investigation of sepsis and help in determining when to discontinue treatment. 

Quick Answers for Clinicians

What are the risk factors for neonatal sepsis?

Major risk factors for neonatal sepsis include preterm birth, low birth weight, maternal colonization of group B streptococcus (GBS), the most common etiologic agent of sepsis,  and chorioamnionitis.   

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.  

What role does laboratory testing play in diagnosing neonatal sepsis?

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 for investigating the severity of sepsis and for monitoring therapeutic response. 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 a baseline to assess therapeutic response.

What role do acute phase markers such as procalcitonin and C-reactive protein play in a neonatal sepsis workup?

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 is helpful in ruling 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 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.

Clinical Definition

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. 

Laboratory Testing

Initial Workup of Suspected Neonatal Sepsis

Initial, nonspecific testing (eg, urine cultures, white blood cell counts) may prove useful for identifying infants with a low probability of developing sepsis, but not for identifying infants likely to be infected.  

Blood Culture

A single blood culture is used to determine the presence of bacterial infection. The culture should be obtained before beginning treatment. 

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. 

C-Reactive Protein

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. CRP sensitivity is initially low, but improves 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 elevated CRP (≥1.0 mg/dL). 

Procalcitonin

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 appear 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. 

ARUP Lab Tests

Initial, nonspecific testing

May be used 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

Important informationLimited to the University of Utah Health Sciences Center only

May be used to evaluate suspected sepsis

Important informationLimited to the University of Utah Health Sciences Center only

Medical Experts

Contributor

Pearson

Lauren N. Pearson, DO, MPH
Assistant Professor of Clinical Pathology, University of Utah
Laboratory Director for ARUP at University of Utah Health and Huntsman Cancer Institute
Laboratory Director, South Jordan and Sugarhouse Health Center Clinical Laboratories

References

Resources from the ARUP Institute for Clinical and Experimental Pathology®