Mode of acquisition

• Transplacental – Infections include Toxoplasma gondii (Toxoplasmosis), Treponema pallidum (congenital syphilis), Listeria monocytogenes, Plasmodium falciparum (malaria), rubella and cytomegalovirus (CMV).
• Ascending maternal infection – This occurs usually after prolonged rupture of membranes with subsequent chorioamnionitis and foetal infection 
• Perinatal acquisition – These are acquired during birth via the haematogenous or genital route. These include Human immunodeficiency virus (HIV), Herpes zoster virus (HZV), Hepatitis B virus (HBV) and Chlamydia trachomatis.
• Postnatal transmission – These are acquired via breast-feeding, and direct inoculation due to harmful local practices such as tribal marks, uvulectomy, and circumcision made with unsterile sharps.

Classification 

Neonatal infections or sepsis can be broadly categorized into early-onset infections (i.e., occurring within the first 72 hours of life) and late-onset infections (i.e., occurring after 72 hours). Early-onset infections are often acquired transplacentally, via ascending maternal infections, haematogenously or during delivery, whereas late-onset infections may be acquired from the community or the hospital environment.

Symptoms

The clinical presentation of neonatal infections is often nonspecific and can overlap with other neonatal conditions, making diagnosis challenging. Common symptoms include fever or hypothermia, respiratory distress, lethargy or irritability, jaundice, poor feeding and vomiting, apnea and seizures.

Clinical Findings

Clinical findings may vary depending on the infection's severity and aetiology. Periumbilical erythema or umbilical pus might be evident if the portal of entry is the umbilicus. Other notable findings include:

• Signs of systemic spread – Pyrexia, hyperthermia or hypothermia, hypotension, bradycardia, and reduced peripheral perfusion.
• Neurological signs – Abnormal reflexes, bulging fontanelle, and abnormal posturing may suggest meningitis.
• Skin changes – Petechiae or purpura especially when complicated by thrombocytopaenia
• Respiratory signs – Decreased breath sounds, crackles, or wheezing may be noted on auscultation in cases of pneumonia.
• Gastrointestinal sign – Include abdominal distension and hepatosplenomegaly. The latter is mostly notable for congenital infections such as syphilis and toxoplasmosis

Differential Diagnoses

Neonatal infections present with nonspecific symptoms which could overlap with other clinical conditions hence, a broad range of differential diagnoses must be considered. These include transient tachypnea of the newborn, respiratory distress syndrome, congenital pneumonia, hypoxic-ischemic encephalopathy, congenital heart disease, metabolic derangement, pyelonephritis, inborn errors of metabolism

Investigations

Timely and accurate diagnosis of neonatal infections is crucial for effective management. Specific investigations include:

• Blood cultures with antibiotic sensitivity patterns, cerebrospinal fluid analysis (including culture) for suspected cases of meningitis, urine culture (especially useful in late-onset infections to detect urinary tract infections) and viral studies which involve PCR tests to identify viral pathogens such as Herpes Simplex Virus and CMV.

Other supportive investigations include:

• Complete Blood Count (CBC), C-reactive protein and procalcitonin – These tests help assess the inflammatory response and guide the diagnosis of sepsis. The CBC is affordable and readily available in low-resource settings. The parameters of the CBC are the basis for the Hematological Sepsis Score (HSS), (Table I) which is useful in the diagnosis of early sepsis. The HSS has an overall score of 8; sepsis is unlikely if the score is ≤2, it is possible with 3 to 4 and very likely with scores ≥ 5.
• Chest X-ray – Indicated in cases of respiratory distress to evaluate for pneumonia or other respiratory conditions.
• Blood glucose – Both hypoglycaemia and hyperglycaemia are known to complicate neonatal infections and would worsen outcomes.
• Oxygen saturation

Table I: Hematological Sepsis Score

Management

The management of neonatal infections requires prompt initiation of appropriate therapy to reduce morbidity and mortality. A high index of suspicion is important, and this is premised upon risk factors such as prolonged rupture of membrane, chorioamnionitis, maternal fever, prematurity, prolonged labour, low birthweight etc. Key components of management include:

• Antibiotic therapy – Empirical broad-spectrum antibiotics are typically initiated while awaiting culture results. Common regimens include ampicillin and gentamicin for early-onset sepsis, with modifications based on culture and sensitivity results.
• Other specific antimicrobial therapies might be indicated such as antiviral agents like acyclovir in cases of confirmed viral HSV or antifungal agents like Amphotericin B for systemic fungal infection.
• Supportive care – This includes maintaining adequate oxygenation, fluid balance, and thermoregulation. Neonates may require respiratory support, intravenous fluids, nutritional support and total parenteral nutrition if available.
• Monitoring – Continuous monitoring of vital signs, laboratory parameters e.g., blood glucose, and clinical status is essential to adjust therapy and detect complications early.

Prognosis and Follow-Up

The prognosis of neonatal infections depends on the infection's severity, the timeliness of intervention, and the neonate's gestational age and overall health. Preterm infants and those with severe infections such as meningitis or septicaemia have a higher risk of mortality or long-term complications, including neurodevelopmental impairments, hearing loss, and chronic lung disease. Regular follow-up is crucial for monitoring growth, development, and the early identification of potential complications. Early intervention programs may be needed for those with developmental delays or other long-term sequelae.

Prevention and Control

Preventing neonatal infections involves a combination of prenatal care, intrapartum management, and postnatal interventions. Key strategies include:

• Maternal screening and treatment – Routine screening for GBS in pregnant women and intrapartum antibiotic prophylaxis significantly reduce the risk of early-onset GBS infection.
• Prevention of chorioamnionitis – Penicillins remain the recommended antibiotic regimen for this purpose.
• Aseptic techniques – Adherence to strict aseptic techniques during delivery and in neonatal care units is critical to preventing nosocomial infections.
• Promotion of breastfeeding – Breastfeeding provides immunity (passive and active) and reduces the risk of common infections such as diarrhea disease, respiratory infections, necrotizing enterocolitis and sepsis.
• Public health interventions – Improving access to clean water, sanitation, and healthcare services in resource-limited settings is essential for reducing the global burden of neonatal infections.