By Joshua Easter, MD, MSc
University of Virginia Health System emergency physician and UVA School of Medicine associate professor
Case: A previously healthy 21-day-old female presents to the ED with crying. Over the last 48 hours she has been fussier than usual but consoles with feeding and swaddling. She has not had a fever or any infection signs or symptoms. She was born full-term via a spontaneous vaginal delivery. On physical examination she has a rectal temperature of 35.9 degrees C, heart rate of 168, respiratory rate of 36, and oxygen saturation of 100%. She is happily swaddled in a blanket, and her examination is normal. What is your next step in managing this infant?
Hypothermia in an infant <3 months of age is a potential indicator of sepsis, which can be life threatening. In infants <48 hours of age, hypothermia is highly associated with serious bacterial infections, including urinary tract infections, bacteremia, and meningitis. Hypothermia can also be benign; infants are unable to regulate their temperature as well as older children, resulting in transient environmental hypothermia that resolves when removed from the cold environment (e.g., infant outside without adequate clothing or blankets). The strength of the association between hypothermia and serious bacterial infection in older neonates presenting to the ED is unclear. Prior single center studies have reported a wide range for the prevalence of serious bacterial infection in hypothermic neonates, ranging from 2-8% (Ramgopal, 2019, Wood, 2018, Perry, 2018). The frequency of diagnostic evaluation for infants presenting to the ED with hypothermia is also quite varied, ranging from 25% to 80% (Perry, 2018; Ramgopal, 2020).
Ramgopal et al. studied 3,565 children ≤90 days old with a discharge or admitting diagnosis of hypothermia. They reviewed data from 2009-2018 in the Pediatric Health Information System (PHIS) administrative database for ED visits at 40 children’s hospitals in the United States. The database included diagnostic testing on blood, urine, cerebrospinal fluid, and chest radiography. The World Health Organization defines hypothermia as <36.5oC, while the Pediatric Sepsis Consensus Conference defines it as <36.0oC. However, the authors did not define an exact cutoff for this study. The primary outcome measure was death, an ICD code consistent with herpes simplex virus (HSV) infection, or serious bacterial infection, as defined by urinary tract infection, bacteremia, meningitis, or pneumonia.
Most of the infants with hypothermia were young, with nearly two thirds (65%) ≤1 week old and 91% ≤30 days old. Most patients had blood (81%) and urine (80%) testing, and 85% were admitted to the hospital. Less had cerebrospinal fluid obtained (42%), chest radiography (31%) or any form of HSV testing (30%). Younger children were more likely to have testing performed, including cerebrospinal fluid acquisition, and to be admitted to the hospital.
A significant proportion (9%) of neonates with hypothermia had a serious infection. 8% of all patients had serious bacterial infection, with bacteremia (6%) being most common. Infants were much less likely to have HSV (0.2%) or die (0.2%). Children with chronic complex medial problems were more likely to have serious infections. Older infants were as likely as young infants to have serious bacterial infections. The risks of serious bacterial infection and mortality associated with hypothermia were similar to the risks reported in studies of neonates with fever.
The database employed in this study did not include any other clinical variables and therefore could not identify clinical predictors of serious bacterial illness. In a subsequent retrospective analysis of 116 infants £60 days old presenting to a single ED with a rectal temperature of ≤36.0 degrees C, Kasmire et al. identified several clinical predictors for serious infection (Kasmire, 2021). They reviewed the charts of infants with hypothermia and found infants with serious infection were more likely to be premature, have apnea, poor feeding, lethargy, or ill appearance. However, their conclusions are limited, as only 3 infants had serious bacterial infections.
While less common than fever in infants, hypothermia is associated with serious infection. Given this risk, we recommend acquiring blood and urine on most infants ≤60 days with a rectal temperature ≤36.5 degrees C. As serious endocrine problems can also lead to hypothermia, it is important to check electrolytes and thyroid function. If the infant has any other concerning historical or physical examination features, they should be admitted to the hospital. Ill appearing infants should have cerebrospinal fluid obtained, including HSV testing. Well appearing infants with transient hypothermia that resolves after being removed from a cold environment may not necessarily require further testing or observation.
Based on the evidence: Your patient looks well but is hypothermic. Given she is swaddled in a blanket, it is unlikely her hypothermia is environmental. Recognizing the risk of serious infection, you obtain blood and urine studies. The patient has normal electrolytes and thyroid function tests, a leukocytosis, and a negative urinalysis. You transfer her to a pediatric hospital for admission, where she remains well appearing. After 48 hours, her blood and urine culture do not show any growth, and she is discharged.
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