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Identifying Infants at Low Risk for Neonatal Herpes Simplex Virus Infection
Keerti L Dantuluri1, Nathaniel S O'Connell2, Gang Liu3
1Department of Pediatrics, Division of Pediatric Infectious Diseases, Wake Forest University School of Medicine, Levine Children's Hospital at Atrium Health, Charlotte, NC, United States.
Background:
Neonatal herpes simplex virus (HSV) infection is rare but associated with high rates of morbidity. Recent guidelines recommend considering HSV in infants ≤21 days of age presenting for sepsis evaluations with certain risk factors. However, limited data exist on the value of these risk factors in stratifying the risk for neonatal HSV infection.
Methods:
We conducted a retrospective case-control study of infants ≤42 days of age who presented between January 1, 2008 and December 31, 2023 for sepsis evaluations to identify infants at low risk for neonatal HSV infection. We used Firth logistic regression to measure the odds ratio of the presence of high-risk criteria between infants without and those with HSV infection. High-risk criteria included skin vesicles, seizures, elevated alanine aminotransferase (ALT), thrombocytopenia, cerebrospinal fluid (CSF) pleocytosis, and/or critical illness. We matched each case with control patients without neonatal HSV infection admitted within 45 days of the case. For each case, we identified 2 controls from group A, which included patients who tested negative for HSV, and 2 controls from group B, who may or may not have undergone HSV testing, but tested negative if they did.
Results:
Thirty-two cases and 128 controls (64 in group A and 64 in group B) were identified. The mean age of cases was 14.3 days. The majority of cases were female, White, non-Hispanic, and born vaginally at term gestation. Controls, or infants without HSV, had lower prevalence of seizures, skin lesions, CSF pleocytosis, elevated ALT, thrombocytopenia, or critical illness compared to infants with HSV. The adjusted odds ratio of a control patient having at least 1 risk factor was 0.07 (95% CI, 0.01-0.3) and 0.02 (95% CI, 0-0.08) for control groups A and B, respectively, compared to cases.
Conclusions:
Among infants presenting for neonatal sepsis evaluations, those without HSV infection are unlikely to present with seizures, skin lesions, elevated ALT, thrombocytopenia, CSF pleocytosis, or critical illness compared to infants with HSV. The lack of these criteria can be used to guide targeted evaluation and management of neonatal HSV infection to minimize testing and treatment of low-risk infants.
