Incidence, risk factors, and costs of neonatal enterovirus hospitalizations in Denmark

BACKGROUND: Enterovirus (EV) infections cause a range of illnesses in neonates, from mild febrile episodes to life-threatening conditions. This study assessed incidence, risk factors, and hospitalization costs of neonates with EV infections in Denmark. METHODS: We used register data on the full population of Denmark from 2015 through 2023, covering 544,168 neonates. The International Classification of Diseases (ICD-10) identified severe EV disease. Risk factors, including gestational age, parity, and birth month, were analyzed using logistic regression in a case-control framework, with birth month as a proxy for EV seasonality. RESULTS: A total of 181 hospital admissions of neonates with an ICD-10 code of EV infection and/or an EV positive polymerase chain reaction (PCR) test were included. The overall incidence was 34 per 100,000 live births. Most cases (147; 82%) occurred June-November, and birth month was significantly associated with EV infection. EV infections involved the central nervous system (CNS) in 87 cases (48%) and sepsis in 36 (20%). EV was associated with higher parity; affected neonates were more often later-born than those without neonatal hospitalizations (OR: 2.39, 95% CI: 1.65-3.49). Total hospitalization costs were €5.3 million, averaging €29,213 per patient. CONCLUSION: Neonatal EV infections in Denmark are rare but can be clinically severe and economically burdensome. Birth month and parity are significant risk factors, reflecting seasonal transmission and household exposure. These findings highlight the need for heightened clinical awareness and preventive strategies, particularly during high-risk months.