Sepsis is a leading cause of mortality in neonates, estimated to occur in one to eight out of every 1,000 births. (WHO 2020; Better Safer Care 2021).
With a relatively weak immune system, newborn infants less than 28 days old are particularly vulnerable to infection entering the bloodstream and causing sepsis.
It’s a condition that not only causes significant morbidity and mortality but one that remains stubbornly difficult to diagnose and treat.
Defining Neonatal Sepsis
There are two categories of neonatal sepsis based on the time of presentation after birth:
Early-onset sepsis (EOS) refers to sepsis in neonates within the first 48 hours of life.
Late-onset sepsis (LOS) refers to sepsis that occurs after the first 48 hours of life.
(Better Safer Care 2021)
Early-Onset Sepsis
EOS is a potentially fatal condition associated with birth canal organisms that are acquired in utero or during delivery (LaMonica 2020). According to Strunk et al. (2018), EOS affects about 0.3 to 0.8 of every 1,000 infants born at or after 35 weeks gestation in developed countries.
Typically, EOS is acquired from the mother and usually presents after either:
Preterm delivery
Rupture of membranes that lasts longer than 24 hours
Infection of the placenta tissues and amniotic fluid (chorioamnionitis)
Frequent vaginal examinations during labour.
(Vera 2019)
Both term and preterm infants with EOS present with respiratory distress, which can progress quickly to multisystem involvement within the first 24 hours of life (LaMonica 2020).
Late-Onset Sepsis
LOS is acquired after delivery and typically presents after the first 48 hours of life (Better Safer Care 2021). Infection is caused by nosocomial acquired microorganisms (LaMonica 2020) and is seen more commonly in premature and low birth weight (LBW) infants.
Late-onset sepsis is usually acquired in one of the following ways:
Contaminated hospital equipment
Exposure to medicines that lead to antibiotic resistance
Leaving a catheter in a blood vessel for a prolonged time
A prolonged hospital stay.
(Vera 2019)
Why are Neonates at Risk of Sepsis?
Neonates are susceptible to infections during the perinatal period due to the immaturity of their immune systems (LaMonica 2020).
Orgamisms such as Escherichia coli may be associated with neonatal sepsis.
Organisms Commonly Associated With Early-Onset Sepsis
Group B Streptococcus
Escherichia coli
Listeria monocytogenes (less common)
Other streptococci including S. pyognes, viridans group streptococci and S. pneumonia
Enterococci
Non-Typable Haemophilus influenza.
(LaMonica 2020; Better Safer Care 2021)
Organisms Commonly Associated With Late-Onset Sepsis
Cross-infection from staff and the infant’s parents
Malformations (e.g. urinary tract anomalies or neural tube defects).
(Better Safer Care 2021)
Recognition of Systemic Neonatal Sepsis
Rapid recognition of sepsis is crucial, as if left untreated it can lead to serious consequences (Better Safer Care 2021).
However, while it is important to identify even subtle signs, avoid over-diagnosing. In most cases, an infant with a fever does not have sepsis (RCHM 2020).
Note that the signs of neonatal sepsis may appear non-specific, as they are clinically similar to the symptoms of other conditions such as cardiac or respiratory failure and metabolic disorders (Better Safer Care 2021).
General signs
Maternal gut feeling that something is ‘not quite right’
Pale skin
Lethargy
Jaundice
Temperature instability
Fever (however, one-third of cases do not present with fever)
Hypothermia
Low tolerance for handling
Hypoglycaemia or hyperglycaemia
Blood gas issues (e.g. acidosis, lactate accumulation)
Respiratory signs
Rapid respiratory rate
Apnoea
Grunting
Blue skin
Cardiovascular signs
Tachycardia
Bradycardic episodes
Poor perfusion
Hypotension
Cutaneous signs
Petechiae
Bruising
Bleeding from puncture sites
Gastrointestinal signs
Poor feeding
Vomiting
Distension of the abdomen
Intolerance to feeding
Bilious aspirates or vomits
Loose stools
Central nervous system signs
Lethargy
Irritability
Seizures
(Better Safer Care 2021)
Swift and Skilful Management is Essential
Despite medical advances, neonatal sepsis remains a leading cause of neonatal mortality. Early recognition, diagnosis and treatment of this serious infection remains a challenge, yet prompt and skilful management is essential to avoid the risk of permanent morbidity or mortality (Rozensztrauch et al. 2018).
Singh et al. (2020) suggest that although specific treatment regimes for neonatal sepsis differ based on various risk factors, empiric treatment with antibiotics should generally be started as soon as sepsis is clinically suspected, even before confirmatory laboratory data becomes available. With mortality rates that are inversely proportional to gestational age, preterm infants are particularly vulnerable and often suffer impaired neurodevelopment or vision impairment.
To date, no effective treatments exist for sepsis beyond antimicrobials and supportive care. With no guaranteed means of early recognition or diagnosis, antibiotics tend to be given as soon as a case of early-onset sepsis is suspected. Yet, as Wynn and Polin (2017) point out, this policy may lead to potential harm, as unnecessary exposure to antibiotics can increase the risk of subsequent short-term and long-term problems. They go on to say that although clinical suspicion is required to detect sepsis, less than 9% of blood cultures yield a bacterial pathogen.
Delaying treatment can have devastating consequences, yet the early and accurate diagnosis of sepsis is difficult and often has limited accuracy. It’s only as time progresses and laboratory results become available that the management of this challenging condition can be refined.
Investigations for Neonatal Sepsis
General tests
Blood gases
Serum electrolytes
True blood glucose
Infection-related tests
Non-specific markers C-reactive protein (CRP)
Full blood examination (FBE)
Tests to identify the infective organism
Early-onset sepsis:
Blood culture
Lumbar puncture (LP)
Late-onset sepsis:
Blood culture
SPA specimen of urine
LP (only if deemed appropriate)
Non-NICU infants suspected of being septic:
LP to exclude CNS infection
Infants in NICU:
LP (only if deemed appropriate)
(Better Safer Care 2021)
Conclusion
Today, sepsis remains a significant contributor to morbidity and mortality in neonates (Singh et al. 2020).
Infection rates have shown modest reductions in recent years, likely due to ongoing quality improvement measures within the neonatal unit. Despite this, there have been minimal improvements in clinical management, outcomes and accuracy of diagnostic testing options over the last three decades (Wynn 2016).
It’s possible that future research will help identify clear early warning signs that can lead to a formal diagnosis, but for now, many challenges remain in both the diagnosis and management of sepsis in the neonate.
Strunk, T, Buchiboyina, A, Sharp, M, Nathan, E, Doherty, D & Patole, S 2018, 'Implementation of the Neonatal Sepsis Calculator in an Australian Tertiary Perinatal Centre', Neonatology, vol. 113, no. 4, pp.379-382, https://pubmed.ncbi.nlm.nih.gov/29514161/
Wynn, J L & Polin, R A 2017, 'Progress in the Management of Neonatal Sepsis: The Importance of a Consensus Definition', Pediatric Research, vol. 83, no. 1, pp.13-15, viewed 3 March 2021, https://www.nature.com/articles/pr2017224
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