OBJECTIVE: The objective of this study was to generate updated estimates for the incidence rate, cost burden, and case fatality rate (CFR) of neonatal herpes simplex virus (nHSV) infections in the US in 2019. METHODS: A nationally representative sample of US pediatric discharges was assessed using data from the Healthcare Cost and Utilization Project Kids' Inpatient Database to estimate the incidence, costs, and fatality of nHSV in 2019. Cases were estimated using herpes simplex virus International Classification of Diseases, Tenth Revision, Clinical Modification codes (B00.xx, A60.xx, or P35.2) among infants aged 28 days or younger admitted to the hospital and with hospital stays more than 5 days or resulting in death. A matching algorithm was developed to deduplicate records of readmissions or transfers from another hospital. Estimates were generated overall and by sociodemographic factors including race, US region, primary payer, and median household income. RESULTS: In total, 561 nHSV cases were estimated in the US in 2019, resulting in an incidence rate of 15.7 per 100 000 hospital births. The highest incidence rate was in the South (21.3
95% confidence interval [CI], 19.0-23.9) and in infants born to Black birth parents (27.3
95% CI, 22.8-32.4). The total cost to the US health care system was estimated at 8.9 million. The CFR among infants with nHSV was estimated to be 4.6%. CONCLUSION: This study updates the incidence rate, cost burden, and CFR of nHSV in 2019, an increase compared with past estimates, and highlights the racial and geographic disparities across the US. Public health interventions for early detection and prevention are critical to mitigate these disparities.