How does hypothermia increase the risk of sepsis in neonates?

Hypothermia as a Risk Factor for Sepsis in Neonates

Hypothermia significantly increases the risk of sepsis in neonates through multiple physiological mechanisms including impaired immune function, altered coagulation, and vascular dysfunction. 1

Relationship Between Hypothermia and Sepsis

• Admission hypothermia (temperature <36°C) in neonates is strongly associated with late-onset sepsis, as demonstrated by multiple observational studies 1
• Hypothermia serves as both a risk factor for developing sepsis and can be an early clinical manifestation of sepsis in neonates 2
• The relationship appears dose-dependent, with an increased risk of adverse outcomes including sepsis for each 1°C below 36.5°C body temperature 1

Physiological Mechanisms

Immune System Dysfunction

• Hypothermia impairs neutrophil function and migration, reducing the neonate's ability to fight bacterial infections 3
• Cold stress alters cytokine production and cellular immune responses, compromising the neonate's defense against pathogens 3
• Hypothermia affects phagocytosis efficiency, making it harder for the immune system to clear bacteria 4

Vascular and Circulatory Effects

• Hypothermia causes peripheral vasoconstriction, which can lead to tissue hypoxia and impaired delivery of immune cells to sites of infection 3
• Endothelial activation markers (like fractalkine) are increased in hypothermic states, suggesting vascular dysfunction plays a role in hypothermia-associated sepsis 3
• Reduced tissue perfusion creates environments favorable for bacterial growth 1

Metabolic Derangements

• Hypothermia is significantly associated with hypoglycemia in neonates, which further compromises immune function 1
• Metabolic acidosis from hypothermia creates conditions that favor bacterial growth 1
• Altered coagulation pathways during hypothermia may contribute to microvascular dysfunction 3

Clinical Implications

• Neonates with hypothermia have a substantial risk for serious bacterial infection (SBI), with studies showing 7.9-8.0% prevalence of SBI in hypothermic neonates 4, 5
• Types of serious infections associated with hypothermia include urinary tract infections, bacteremia, meningitis, and disseminated herpes simplex virus 4
• Hypothermia with temperature ≤34.4°C appears particularly concerning for serious infection 4

Risk Factors for Hypothermia-Associated Sepsis

• Prematurity significantly increases risk due to larger surface area-to-volume ratio and immature thermoregulation 1
• Low birth weight/low body mass index increases susceptibility to both hypothermia and sepsis 3
• Cardiovascular insufficiency and hypertension are risk factors for hypothermic sepsis 3
• Additional clinical features that increase sepsis risk in hypothermic infants include poor feeding, lethargy, ill appearance, and respiratory signs 6

Prevention and Management

• Maintaining normothermia (36.5-37.5°C) is strongly recommended for all neonates to reduce mortality and morbidity, including sepsis 1
• Temperature should be recorded as both a predictor of outcomes and a quality indicator 1
• Strategies to prevent hypothermia include radiant warmers, plastic wrap with caps, thermal mattresses, and warmed humidified resuscitation gases 1
• For resource-limited settings, clean food-grade plastic bags and skin-to-skin contact are reasonable interventions to prevent hypothermia 1

Clinical Pitfalls to Avoid

• Do not dismiss mild hypothermia (36-36.4°C) as clinically insignificant; even mild hypothermia increases sepsis risk 1
• Avoid focusing solely on temperature without considering other clinical signs of sepsis 6
• Be aware that hypothermia may mask fever in neonates with sepsis, potentially delaying diagnosis 2
• Recognize that hypothermia with serious infection often presents with other concerning features rather than as an isolated finding 6
• Avoid excessive rewarming rates in severe hypothermia as this can lead to complications 7