Invasive Neonatal Enterovirus Infection: A Case Series and Review of the Literature

Abstract

Highlights What are the main findings? • Nine neonates with invasive enterovirus infection presented predominantly with meningitis; one developed concurrent myocarditis. All infants received IVIG and had favorable outcomes at discharge.• Symptom onset ranged from the second to the thirty-fourth day of life; eight of nine infants developed symptoms after 72 h, a pattern compatible with either intrapartum-acquired infection (given the typical enteroviral incubation period) or postnatal acquisition, which this case series cannot distinguish with certainty. What are the implications of the main findings? • A high clinical index of suspicion for NEVI is essential, particularly when maternal or familial viral symptoms are reported around delivery, given the clinical overlap with bacterial sepsis.• Early molecular diagnosis (RT-PCR) allows timely diagnosis and initiation of supportive management, including IVIG; however, IVIG efficacy in NEVI has not been established in controlled studies and warrants evaluation through randomized trials. Abstract Background/Objectives: Enteroviruses (EV) cause neonatal infections with variable incidence and severity, occasionally progressing to invasive disease. This study reports the experience of two Italian neonatal centers with invasive neonatal EV infection (NEVI), describing management and outcomes in relation to the existing literature. Methods: This retrospective study included neonates diagnosed with NEVI. Data related to clinical symptoms, treatment and outcomes were reported and compared to those available in the current literature. Results: All nine neonates presented with systemic infection symptoms; onset ranged from the second to the thirty-fourth day of life, with eight of nine infants presenting after 72 h, most following readmission after initial discharge rather than continuous hospitalization from birth. The transmission route (vertical versus horizontal) could not be determined with certainty. All nine neonates had central nervous system infection confirmed by RT-PCR detection of EV in cerebrospinal fluid; two presented seizures or epileptiform abnormalities, and one developed myocarditis. IVIG was administered upon diagnosis. All infants survived to discharge in stable condition; neuroimaging abnormalities were documented in two infants, and long-term neurodevelopmental outcome could not be assessed in most patients due to incomplete follow-up. Conclusions: Invasive NEVI cannot be clinically differentiated from severe bacterial infection, warranting a high index of suspicion, particularly when caregivers report symptoms of viral infection. Further studies are needed to clarify aspects of management, including the potential benefit of IVIG administration.