Define Neonatal Sepsis. Describe its pathogenesis, classification, clinical features and investigations.

Definition

• Neonatal sepsis is a clinical syndrome of systemic illness with bacteraemia occurring in the first 28 days of life, characterised by signs and symptoms of infection with or without a positive blood culture.
• It is a leading cause of neonatal mortality in India, contributing to a large share of preventable newborn deaths.

WHY the Newborn Is Susceptible (pathogenesis)

The neonate — especially the preterm — has an immature immune system and vulnerable barriers:

• Immature innate immunity — reduced neutrophil reserve, impaired chemotaxis and phagocytosis, low complement levels.
• Immature adaptive immunity — low IgG (transplacental IgG mainly transferred in the 3rd trimester → preterm deficient), and IgM & IgA do not cross the placenta, so the newborn cannot fight Gram-negative organisms well.
• Vulnerable barriers — thin skin, the umbilical stump as a portal of entry, and an immature gut mucosa.
• Once organisms invade, a cytokine cascade (TNF-α, IL-1, IL-6) drives the systemic inflammatory response, shock and DIC.

Routes of Infection

• Transplacental (haematogenous) — e.g. Listeria, torch agents.
• Ascending / intrapartum — from the birth canal after rupture of membranes (early-onset).
• Postnatal / nosocomial — from the environment, hands, equipment and invasive lines (late-onset).

Classification

Risk Factors

For early-onset (maternal):

• PROM > 18–24 hours; maternal fever / chorioamnionitis.
• Foul-smelling / meconium-stained liquor; maternal UTI or GBS colonisation.
• Prematurity and low birth weight; unclean or prolonged / instrumental delivery.
• More than 3 vaginal examinations in labour.

For late-onset (baby / environment):

• Prematurity / LBW; prolonged hospital stay; invasive lines & ventilation.
• Poor hand hygiene, overcrowding, prolonged antibiotics, lack of breastfeeding.

Clinical Features

Signs are non-specific and subtle — 'the baby is not doing well'. A high index of suspicion is vital.

• General: lethargy, refusal to feed, poor cry, temperature instability (fever OR hypothermia).
• Respiratory: tachypnoea, grunting, retractions, apnoea, cyanosis.
• CVS: tachycardia, poor perfusion, prolonged CRT, shock, sclerema.
• GIT: vomiting, abdominal distension, diarrhoea, poor feeding, hepatosplenomegaly.
• CNS: lethargy, irritability, seizures, bulging fontanelle, high-pitched cry (meningitis).
• Others: jaundice, bleeding / DIC, petechiae, hypo/hyperglycaemia.

Investigations

Definitive:

• Blood culture — the gold standard (before starting antibiotics; ≥ 1 mL blood).
• Lumbar puncture / CSF study — mandatory in late-onset / positive culture / neurological signs.
• Urine culture (suprapubic / catheter) in late-onset sepsis.

Sepsis screen (supportive; ≥ 2 positive = probable sepsis):

• Total leukocyte count (< 5000 or high); Absolute Neutrophil Count (neutropenia is ominous).
• Immature-to-Total neutrophil (I:T) ratio ≥ 0.2.
• C-reactive protein (CRP) elevated; micro-ESR > 15 mm in the 1st hour.
• Others: procalcitonin, thrombocytopenia, toxic granules, chest X-ray if respiratory.

Management — Supportive Care (equally Important)

• Maintain temperature (warmth), oxygenation, and perfusion (fluid boluses / inotropes for septic shock).
• Maintain euglycaemia; correct electrolyte, acid-base and coagulation abnormalities (FFP/platelets for DIC).
• Continue breast / expressed milk feeds if tolerated; IV fluids if not; nurse in a thermoneutral environment.

Management — Antibiotics (start Empirically After Cultures; Do Not Wait)

• First-line (community EOS): Ampicillin + Gentamicin (add Cefotaxime if meningitis).
• Nosocomial LOS: as per the unit antibiogram — e.g. Piperacillin-tazobactam / Vancomycin + Amikacin, or Meropenem for resistant Gram-negatives; antifungal (fluconazole/amphotericin) if Candida.
• Duration: 7–10 days for sepsis, 14–21 days for meningitis; de-escalate as per culture & sensitivity.
• Adjuncts: IVIG in selected cases; exchange transfusion for sclerema / DIC (not routine).

Complications

• Septic shock and multi-organ dysfunction; DIC and bleeding.
• Meningitis and its sequelae — hydrocephalus, seizures, deafness, developmental delay.
• Pneumonia, necrotising enterocolitis, osteomyelitis / septic arthritis, endocarditis.

Prognosis

Mortality is high, especially in preterm babies, Gram-negative sepsis and meningitis. Early recognition and prompt antibiotics dramatically improve survival. Meningitis survivors need long-term neurodevelopmental and hearing follow-up.

Prevention

• Clean delivery practices (WHO '5 cleans'); asepsis and strict hand hygiene in the nursery.
• Early exclusive breastfeeding; KMC; minimise invasive procedures and rationalise antibiotics.
• Intrapartum antibiotic prophylaxis for GBS-colonised mothers; good antenatal care; antenatal steroids to reduce prematurity morbidity.