Overview

Neonatal sepsis is a severe condition in newborn babies that arises from bacterial, viral, or fungal infections and can cause significant morbidity and mortality. It occurs worldwide in approximately 1 to 50 out of 1000 live births, accounting for 3 to 30% of cases annually.¹⁰ Neonatal sepsis can be classified into two groups: early-onset neonatal sepsis and late-onset neonatal sepsis. In this article, we will explain the classification, risk factors, pathogenesis, clinical symptoms, and prevention methods of neonatal sepsis.

Pathophysiology of neonatal sepsis

Neonatal sepsis stems from a variety of causes such as Group B Streptococcus (GBS), Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus). 

GBS infections are classified clinically into early-onset (within the first 6 days of life) and late-onset (1 month after birth) disease.² In early-onset disease (EOD), infection is transmitted vertically occurring immediately before or during labour and delivery which accounts for 80% of all GBS cases.¹²

The pathogenesis of GBS-EOD infection in neonates involves the establishment of vaginal colonisation in pregnant women, with subsequent transmission to the newborn during childbirth upon passage through the birth canal. GBS gains access to the foetus by ascending into the amniotic cavity illustrated in figure 1 by migrating through the cervix and into the uterus, penetrating gestational tissues.³ Once inside, S.agalactiae can proliferate and colonise the skin or mucous membranes of the foetus by attaching and invading the chorioamniotic membrane.¹ This can lead to inflammation in the foetal membrane where entry into the bloodstream enables S.agalactiae to enter the pulmonary epithelial layer and as a result, foetal lungs are exposed to inflammatory cytokines and mediators via amniotic fluid causing severe complications.⁴

Late-onset disease (LOD) GBS infection occurs when infants are colonised by GBS from the mother's mucosa or other sources after delivery or during postpartum.⁵ The result of the infection is acquired overcoming the epithelial barrier and innate cellular immunity of the infant. It often occurs through horizontal transmission from individuals responsible for the care of the baby, from environmental or nosocomial sources.⁶

Figure 1. Ascending GBS infection migrating through gestational tissues⁸

Risk factors for neonatal sepsis

Infant risk factors¹¹

• Prematurity
• Low birth weight: Preterm low birthweight infants have a 3-10 times higher incidence of infection compared to normal birthweight infants. 
• Birth trauma
• Invasive procedures such as endotracheal intubation or central venous catheterisation
• Prolonged hospitalisation
• Congenital abnormalities Respiratory tract disease
• Metabolic disease

Maternal risk factors⁹

• Urinary tract infection
• Maternal colonisation with GBS, herpes simplex virus or Neisseria gonorrhoeae
• Chorioamnionitis (inflammation of foetal membranes)

Hospital-acquired risk factors¹⁰

• Contaminated medical equipment
• Poor hand hygiene practices
• Overcrowding in neonatal intensive care units

Diagnosis of neonatal sepsis

Early recognition and diagnosis play a crucial role in effectively managing neonatal sepsis. Neonatal sepsis presents with nonspecific signs and symptoms including:¹¹

• Fever
• Lethargy
• Respiratory distress
• Jaundice
• Feeding intolerance

Later complications may include:¹¹

• Cardiac failure
• Renal failure
• Liver dysfunction
• Adrenal haemorrhage

Recognising these clinical manifestations is crucial for initiating further evaluation and timely treatment. Diagnostic evaluation involves a combination of laboratory and molecular methods.

Laboratory methods

The gold standard for the diagnosis of neonatal sepsis is isolating the causative agent in body fluids (blood, urine, cerebrospinal fluid, pleural fluid, joint fluid and peritoneal fluid) that is normally sterile.¹¹ However, blood culture can produce false-negative results if antibiotics were given prenatally to the mother or if the blood sample is collected improperly.¹⁰

Another technique used to screen neonatal sepsis is the use of tracheal aspirate culture to aid diagnosis of babies who need mechanical ventilation as a result of respiratory failure. However, the drawback of this methodology is the risk of colonisation and contamination along with a low diagnostic value.

Other diagnostic techniques include complete blood count, C-reactive protein, imaging studies such as chest X-ray and ultrasound and lumbar puncture.⁹

Molecular methods

The use of molecular methods is critical in recognising the morphological, metabolic or cytopathic features of microorganisms. Molecular techniques are beneficial due to their rapid identification of the types of bacteria (gram-negative and gram-positive) in the diagnosis of sepsis by the detection of microbial nucleic acids. Techniques involve polymerase chain reaction, nucleic acid amplification tests and more.¹¹

Molecular methods provide several advantages over conventional methods which may fail to isolate the pathogen due to prior antibiotic exposure.

Preventative measures

Prevention of early neonatal sepsis

The current strategy to avert GBS-related outcomes is the use of intrapartum antibiotic prophylaxis (IAP). IAP is the administration of intravenous penicillin or ampicillin to GBS carriers to protect new-borns from developing EOD-GBS disease.⁷ This is implemented through a routine culture-based or a risk-based prenatal screening strategy. In a routine culture-based strategy, IAP is administered to women who are colonised with GBS.⁸ In contrast to risk-based strategy, IAP is offered to women who have a history of perinatal GBS infection. The use of IAP has reduced the incidence of EOD but it cannot prevent the risk of ascending infection during pregnancy (figure 1) nor does it have an impact on horizontal transmission routes; therefore, it is ineffective against late-onset GBS infections.⁸

Prevention of late neonatal sepsis

Late neonatal sepsis can be prevented by proper infection control practices before and during delivery. The most effective way to prevent the spread of microorganisms is by washing hands thoroughly or using alcohol gel. The World Health Organization recommends emphasising handwashing to prevent the transmission of germs. Furthermore, promoting the exclusive use of breast milk can also reduce the likelihood of infections by increasing the diversity of intestinal microbiota. Breast milk contains high concentrations of IgA and oligosaccharides, which have anti-infectious properties. It is important to learn the signs of sepsis, see your healthcare provider regularly, practise good hygiene, and seek immediate care if you suspect your baby has sepsis.

Potential prevention in the future

Another prevention tool to reduce global morbidity and mortality is the development of a vaccine involving an efficient transplacental antibody transfer.⁸ The adoption of a GBS vaccine among 70% of the pregnant female population could potentially avert almost 50,000 deaths caused by GBS and prevent over 170,000 preterm births. Therefore, the development of a vaccine can prevent a range of GBS-associated diseases, including EOD and LOD.¹² However, testing various vaccine candidates targeting GBS is facing a multitude of challenges. It has the potential to save lives in the future.

FAQ’s

How do I know if my newborn should be taken to the Emergency Room?

Knowing when to take your newborn to the ER can be crucial for their health and well-being. Here are some signs and symptoms that may indicate the need for immediate medical attention:

1. Difficulty breathing: If your newborn is struggling to breathe or showing signs of respiratory distress it is essential to seek medical help.
2. Persistent fever: A fever in a newborn within the first few months of life with a temperature of 38°C or higher.
3. Persistent vomiting or diarrhoea
4. Seizures in a newborn 

Summary

Neonatal sepsis is a serious condition in the newborn period that requires rapid detection and diagnosis to prevent complications and death. Treatment is crucial for a complete recovery.