How does hypothermia increase the risk of Respiratory Distress Syndrome (RDS), hypoglycemia, Intraventricular Hemorrhage (IVH), and late-onset sepsis in preterm or low-birth-weight infants?

Mechanisms by Which Hypothermia Increases Risk of RDS, Hypoglycemia, IVH, and Late-Onset Sepsis

Hypothermia (temperature <36°C) in preterm and low-birth-weight infants significantly increases the risk of respiratory distress syndrome, hypoglycemia, intraventricular hemorrhage, and late-onset sepsis through multiple physiologic mechanisms that impair metabolic function, increase oxygen consumption, compromise immune function, and disrupt cerebrovascular autoregulation. 1

Respiratory Distress Syndrome (RDS)

Hypothermia increases RDS risk primarily by increasing metabolic oxygen consumption and impairing surfactant production and function:

• Cold stress triggers non-shivering thermogenesis in brown adipose tissue, dramatically increasing oxygen consumption and metabolic rate, which worsens respiratory distress and increases need for respiratory support 1
• Hypothermia impairs surfactant synthesis and function at the alveolar level, reducing lung compliance and increasing work of breathing 1
• Nine observational studies demonstrate a clear association between hypothermia and respiratory disease, with two studies specifically showing decreased respiratory support requirements when temperature maintenance improved 1
• One large randomized controlled trial found that improved admission temperature reduced pulmonary hemorrhage (OR 0.57,95% CI 0.35-0.94), a severe complication of RDS 1

Important caveat: One 2017 Danish study found no statistically significant association after adjusting for confounders, though unadjusted odds ratios were elevated (OR 2.03) 2. However, the 2015 International Consensus guidelines prioritize the preponderance of evidence showing this association 1

Hypoglycemia

Hypothermia causes hypoglycemia through dramatically increased glucose consumption during thermogenesis:

• Cold stress activates brown adipose tissue metabolism, which consumes glucose at accelerated rates to generate heat through non-shivering thermogenesis 1
• Seven observational studies demonstrate a significant association between hypothermia (<36°C) and hypoglycemia in preterm infants 1
• Two studies using historical controls showed improved glycemic control when normothermia was maintained 1
• The American Heart Association emphasizes that blood glucose should be checked immediately in hypothermic infants, as hypoglycemia commonly coexists with hypothermia 3, 4
• This relationship is so strong that persistent hypothermia despite appropriate thermal management should prompt immediate blood glucose assessment 4

Intraventricular Hemorrhage (IVH)

Hypothermia increases IVH risk through disruption of cerebrovascular autoregulation and increased metabolic stress:

• Cold stress causes fluctuations in cerebral blood flow by impairing cerebrovascular autoregulation in the fragile germinal matrix of preterm infants 1
• Increased metabolic demands from thermogenesis cause hemodynamic instability and blood pressure fluctuations that stress the vulnerable periventricular capillary bed 1
• Eight observational studies show hypothermia (temperature <36°C) in preterm infants is associated with increased likelihood of developing IVH 1
• A Korean study of 5,343 VLBW infants found admission hypothermia associated with grade 3 or higher IVH 5
• One California study of 8,782 VLBW infants found moderate hypothermia specifically associated with higher risk of IVH 6

Evidence conflict: Eight other observational studies found no association between hypothermia and IVH, though these were downgraded for indirectness 1. The International Consensus guidelines acknowledge this mixed evidence but emphasize the preponderance supporting the association 1

Late-Onset Sepsis

Hypothermia increases late-onset sepsis risk through immune system impairment and as a marker of underlying infection:

• Cold stress impairs neutrophil function, reduces phagocytic activity, and compromises innate immune responses in preterm infants 1
• Hypothermia disrupts cytokine production and inflammatory responses necessary for fighting bacterial infections 1
• Two observational studies indicate an association between hypothermia on admission and late sepsis 1
• A 2013 study specifically found admission temperatures below 36°C associated with increased late-onset sepsis independent of other risk factors 7
• The American Academy of Pediatrics states that hypothermia in neonates is strongly associated with late-onset sepsis, independent of other risk factors 4

Critical clinical point: Persistent hypothermia despite appropriate thermal management strongly suggests an underlying pathologic process, most commonly sepsis, and should prompt immediate sepsis workup and empirical antibiotics 4

Dose-Response Relationship

The risk increases progressively with greater degrees of hypothermia:

• There is at least 28% increased risk of mortality for each 1°C below 36.5°C body temperature at admission, demonstrating a clear dose-effect relationship 1, 3
• A Korean study found adjusted odds ratios for death increased progressively: 1.38 for 36.0-36.4°C, 1.44 for 35.0-35.9°C, and 1.86 for <35.0°C 5
• This dose-dependent effect extends to morbidities including RDS, hypoglycemia, IVH, and sepsis 1, 5

Clinical Implications

Temperature maintenance between 36.5-37.5°C is essential to prevent these complications:

• The International Consensus on Cardiopulmonary Resuscitation strongly recommends maintaining temperature between 36.5-37.5°C from birth through admission and stabilization 1
• Admission temperature should be recorded as both a predictor of outcomes and a quality indicator 1
• Even mild hypothermia (36.0-36.4°C) should not be dismissed, as it carries increased mortality and morbidity risk 3
• Quality improvement initiatives using standardized protocols have successfully reduced hypothermia rates from 44% to 0% in some centers 7