Recognising Neonatal Sepsis


Published: 28 March 2021

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:

  1. Early-onset sepsis (EOS) refers to sepsis in neonates within the first 48 hours of life.
  2. 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).

neonatal sepsis escherichia coli
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

  • Coagulase negative staphylococcus
  • Staphylococcus aureus
  • Enterococci
  • Multidrug-resistant Gram-negative rods including E. coli, Klebsiella, pseudomonas, enterobacter, citrobacter and serratia
  • Candida.

(LaMonica 2020; Better Safer Care 2021)

Risk Factors for Neonatal Sepsis

General risk factors that may predispose an infant to infection include:

  • Preterm labour
  • Prolonged rupture of membranes (over 12 to 18 hours)
  • Maternal fever including chorioamnionitis, maternal septicaemia and transient bacteraemia
  • Multiple pregnancy
  • Previously infected infant
  • Prematurity
  • Low birth weight
  • Immature immune system of the neonate
  • Premature rupture of the membranes
  • Birth asphyxia (as hypoxia and acidosis may reduce cellular immune functions)
  • Coitus occurring close to delivery, as this carries an uncertain risk for maternal colonisation and ultimately for fetal or neonatal infection
  • Postnatal procedures such as intubation, chest tube insertion, and catheterisation of umbilical vessels
  • Foul-smelling amniotic fluid
  • Low socioeconomic status
  • Maternal malnutrition
  • Lack of prenatal care
  • Maternal substance abuse
  • Maternal urinary tract infection at delivery
  • Peripartum infection
  • Clinical amnionitis
  • Maternal bacterial colonisation.

(LaMonica 2020)

Specific Risk Factors for Early-Onset Sepsis

  • Prolonged rupture of the membranes (longer than 18 hours)
  • Fetal distress
  • Maternal fever of over 38 °C or maternal infection (e.g. urinary tract infection, gastroenteritis)
  • Undergoing several obstetric procedures (including cervical sutures)
  • Preterm delivery
  • Group B streptococcus (GBS) in previous infants
  • GBS bacteria in urine during pregnancy.

(Better Safer Care 2021)

Specific Risk Factors for Late-Onset Sepsis

  • Male neonate
  • Prolonged hospital stay
  • Invasive devices in-situ (e.g. intravenous catheters, endotracheal tubes)
  • 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.

neonatal sepsis newborn infant

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)


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.

Additional Resources



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Anne Watkins View profile
Anne is a freelance lecturer and medical writer at Mind Body Ink. She is a former midwife and nurse teacher with over 25 years’ experience working in the fields of healthcare, stress management and medical hypnosis. Her background includes working as a hospital midwife, Critical Care nurse, lecturer in Neonatal Intensive Care, and as a Clinical Nurse Specialist for a company making life support equipment. Anne has also studied many forms of complementary medicine and has extensive experience in the field of clinical hypnosis. She has a special interest in integrating complementary medicine into conventional healthcare settings and is currently an Associate Tutor, lecturing in Health Coaching and Medical Hypnosis at Exeter University in the UK. As a former Midwife, Anne has a natural passion for writing about fertility, pregnancy, birthing and baby care. Her recent publications include The Health Factor, Coach Yourself To Better Health and Positive Thinking For Kids. You can read more about her work at