Why are preterm babies prone to sepsis?

Why Preterm Babies Are Prone to Sepsis

Preterm infants have fundamentally immature immune systems with reduced innate and adaptive immunity, combined with compromised physical barriers and unavoidable medical interventions that collectively create a perfect storm for infection susceptibility. 1

Immune System Immaturity

The preterm immune system exhibits distinct—not simply deficient—function compared to term infants, which directly increases infection risk 2:

• Smaller pools of monocytes and neutrophils limit the cellular response to pathogens 3
• Impaired pathogen-killing ability of immune cells reduces bacterial clearance 3
• Lower cytokine production limits T cell activation and reduces the ability to fight bacteria and detect viruses 3
• Naive adaptive immunity means preterm infants lack the immune memory and antibody protection that develops in the third trimester 2, 3

Physical Barrier Deficiencies

Preterm infants have multiple anatomical vulnerabilities that facilitate pathogen entry 1:

• Thin, immature skin with compromised barrier integrity allows easier bacterial translocation 1, 4
• Large surface area relative to body mass increases exposure sites for infection 1
• Immature gastrointestinal tract with shorter crypts and villi, reduced mucus production, fewer Paneth cells producing antimicrobial peptides, and increased intestinal permeability 1
• Immature blood vessels in the brain prone to hemorrhage, which can become infected 1

Intrauterine Inflammatory Exposure

The "first inflammatory hit" occurs before birth in many preterm infants 5:

• Intrauterine inflammation is a major contributor to preterm birth itself and causes premature immune activation 3, 5
• Induced immune tolerance from prenatal inflammation leads to reduced newborn immune function 3
• Increased risk of early-onset sepsis is directly associated with chorioamnionitis and intrauterine inflammation 3, 5

Medical Interventions and the "Second Inflammatory Hit"

Necessary medical care paradoxically increases infection risk 1, 5:

• Invasive devices including umbilical venous catheters significantly increase infection risk 1, 6
• Antenatal corticosteroids, while essential for lung maturation, may be immunosuppressive and associated with increased infection risk 3
• Broad-spectrum antibiotics disrupt normal microbiome establishment and select for resistant organisms 1, 4
• Delayed enteral feeding and parenteral nutrition alter gut colonization patterns and increase fungal infection risk 1
• Respiratory support can cause chronic inflammatory lung disease 3

Altered Microbial Colonization

Preterm infants experience abnormal microbiome development that contributes to sepsis risk 1:

• Hospital-specific microbes rather than maternal flora colonize preterm infants 5
• Cesarean section delivery (common in preterm birth) alters normal colonization patterns 3, 6
• Gut dysbiosis has been linked to both necrotizing enterocolitis and late-onset sepsis 1
• Skin microbiome disruption allows pathogenic organisms to dominate, as common sepsis pathogens (particularly coagulase-negative staphylococci) colonize the skin 4, 6

Specific Vulnerabilities by Gestational Age

Very low birth weight infants (<32 weeks, <1000g) face additional risks 1:

• Extreme immune immaturity in infants born before 28 weeks who missed critical third-trimester immune development 1, 5
• Relative hormone deficiencies including thyroid and parathyroid hormones 1
• Reduced glycogen stores leading to hypoglycemia that further compromises immune function 1
• Small blood volume increasing risk of hypovolemic shock 1

Common Sepsis Pathogens in Preterm Infants

The organisms causing sepsis reflect the unique exposures of preterm infants 6:

• Coagulase-negative staphylococci are the most frequently isolated pathogens, particularly with catheter-associated infections 1, 6
• Gram-negative organisms including Pseudomonas aeruginosa, E. coli, and Klebsiella species 7
• Candida species particularly in infants receiving total parenteral nutrition and prolonged antibiotics 8

Critical Clinical Implications

The combination of immune immaturity, barrier defects, inflammatory priming, and unavoidable medical interventions creates a 16.6% infection rate in late preterm infants (32-36 weeks), with 90% occurring in the first 72 hours of life 6. For extremely preterm infants, the risk is substantially higher, with infection remaining a leading cause of morbidity and mortality 2, 5.