550 - Cold Clues: Clinical characteristics and mortality among hypothermic infants with herpes simplex virus infection

Publication Number: 2535.550

Leslie A. Hueschen, University of Missouri-Kansas City School of Medicine, Kansas City, MO, United States; Sriram Ramgopal, Ann & Robert H. Lurie Children's Hospital of Chicago, CHICAGO, IL, United States; Hoi See Tsao, University of Texas Southwestern Medical Center, Dallas, TX, United States; Kelly R.. Bergmann, Children's Minnesota, Minneapolis, MN, United States; AG Nuwan Perera, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; Amy D. Thompson, Sidney Kimmel Medical College at Thomas Jefferson University, Wilmington, DE, United States; Paul L. Aronson, Yale School of Medicine, New Haven, CT, United States; Erin J. Meyer, UMass Memorial Children's Medical Center, Natick, MA, United States; Sara Holmstrom, Indiana University School of Medicine, Indianapolis, IN, United States; Paria M. Wilson, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Alexander Stephan, NewYork-Presbyterian/Weill Cornell Medicine, New York, NY, United States; Jerri Rose, UH Rainbow Babies & Children's Hospital, Cleveland, OH, United States; Marsha Elkhunovich, Keck School of Medicine of the University of Southern California, Children's Hospital Los Angeles, sherman oaks, CA, United States; Theodore Heyming, Rady Children's Hospital Orange County, Orange, CA, United States; Collin Huth, UH Rainbow Babies & Children's Hospital, Cleveland, OH, United States; Alexander Rogers, University of Michigan Medical School, Ann Arbor, MI, United States; Oluwakemi Badaki-Makun, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Andrea T. Cruz, Baylor College of Medicine, Houston, TX, United States; Christopher M.. Pruitt, Medical University of South Carolina College of Medicine, Charleston, SC, United States; Naghma S. Khan, Emory University School of Medicine, Atlanta, GA, United States; Laura Sartori, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Wendi Wendt, Medical College of Wisconsin, Milwaukee, WI, United States; Carolyn K. Holland, University of Florida College of Medicine, Gainesville, FL, United States; Adam Isacoff, University of Louisville School of Medicine, Louisville, KY, United States; Shaila Zaman, Baylor College of Medicine, Houston, TX, United States; Jamie Holland, Northwestern University The Feinberg School of Medicine, Chicago, IL, United States; Jonathan R. Higgins, University of Colorado Anschutz School of Medicine, Aurora, CO, United States; Alexandra T. Geanacopoulos, Boston Children's Hospital, Jamaica Plain, MA, United States; Nathan M. Money, University of Utah School of Medicine, Salt Lake City, UT, United States; Stacy Ulrich, University of California, San Diego School of Medicine, San Diego, CA, United States; Sofia Grigoria Athanasopoulou, Yale School of Medicine, New Haven, CT, United States; Madeline R. Field, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; YU HSIANG J. LO, NewYork-Presbyterian Hospital Columbia University Medical Center, New York, NY, United States

Background: Hypothermia is considered a risk factor for neonatal herpes simplex virus (HSV) infection. Research evaluating HSV in infants with hypothermia is limited.

Objective: To describe the prevalence, clinical profile, and outcomes of hypothermic infants with HSV infections presenting to the pediatric emergency department (ED).

Design/Methods: We performed a retrospective cross-sectional study of infants (≤90 days of old) with hypothermia (rectal temperature < 36.5 °C) presenting to one of 28 tertiary pediatric EDs between January 1, 2013, and December 31, 2022, excluding infants with fever, transfer from another ED, technology dependence, trauma, skin/soft tissue infections, or presenting in cardiac arrest. We described laboratory and clinical characteristics of HSV-positive compared to HSV-negative hypothermic infants.

Results: We analyzed 57,640 infants with hypothermia in the ED (median age 23 days [IQR 6-50]; 53.0% male). HSV Polymerase Chain Reaction (PCR)-positivity from at least one testing site occurred in 126 infants, yielding a prevalence of 0.22% (95% confidence interval [CI] 0.18-0.26%). Of these, 98 (77.8%) had positive cerebrospinal fluid (CSF), 26 (20.6%) had positive blood, and 21 (16.7%) had positive surface HSV PCR testing. The median age of HSV-positive infants was 6 days (IQR 4-12) with a maximum age of 80 days (Table 1). The median minimum temperature of HSV-positive infants was 35.8°C (IQR 35.4-36.2°C). Laboratory studies obtained in hypothermic infants with HSV infection varied (Table 2), and one HSV-positive infant had concurrent bacteremia. Compared to infants without HSV, infants with HSV were younger (6 vs 23 days; p < 0.001), had lower minimum rectal temperature (35.8 vs 36.3°C; p< 0.001), higher rates of intensive care unit admission (57.9 vs 14.3%; p< 0.001), and higher aspartate aminotransferase (87 vs 47 U/L; p< 0.001). Of infants with HSV, 7/126 died (5.6%; 95% CI 2.3-11.3%), compared to 127/57,515 deaths (0.22%; 95% CI 0.18-0.26%) among infants without HSV (p < 0.001).

Conclusion(s): Among hypothermic infants in the ED, HSV is uncommon, but infants with HSV have significant higher mortality compare to hypothermic infants without HSV. Infants with hypothermia and neonatal HSV have distinct clinical characteristics compared to other infants with hypothermia. Further study is needed to delineate risk stratification of hypothermic infants at risk of HSV infection.

Table 1. Demographics of hypothermia infants with and without herpes simplex virus (HSV) infection
Table 1. Demographics of hypothermia infants with and without herpes simplex virus (HSV) infection

Table 2. Laboratory testing for hypothermic infants with and without herpes simplex virus (HSV) infection
Table 2. Laboratory testing for hypothermic infants with and without herpes simplex virus (HSV) infection