Neurodevelopmental Outcomes of Infants Younger Than 90 Days Old Following Enterovirus and Parechovirus Infections of the Central Nervous System
Open accessAbstract
Enteroviruses (EVs) and human parechoviruses (HPeVs) are a major cause of central nervous system (CNS) infection in young infants. They have been implicated in neurodevelopmental delay, however limited data are available. The aim of this study is to describe the clinical outcome of young infants and to assess and compare the medium-term neurodevelopment following CNS infections caused by EV and HPeV. A multicentre observational ambispective study was conducted between May 2013 and March 2018. Children under 3 months of age with EV or HPeV CNS infection excluding encephalitis were included. Infants were contacted 1 year after the acute infection and their neurological development was evaluated using the Ages and Stages Questionnaire-3 (ASQ-3). If any area assessed was abnormal during the first round of tests, a second round was completed 6 to 12 months later. Forty-eight young infants with EV and HPeV CNS infection were identified: 33 (68.8%) were positive for EV and 15 (31.3%) for HPeV. At first assessment 14 out of 29 EV (48.3%) and 3 out of 15 HPeV (20%) positive cases presented some developmental concern in the ASQ-3 test. EV-positive infants showed mild and moderate alteration in all domains analyzed and HPeV-positive infants showed mild alterations only in gross and fine motor domains. Significant alterations in communication were observed in EV-positive but not in HPeV-positive infants (31 vs. 0%,p= 0.016). At second assessment 4 out of 13 EV-positive patients (30.8%) showed mild to moderate concerns in communication and gross motor function domains and 3 out of 13 (23.1%) showed significant concern in fine motor function. Although CNS infections without associated encephalitis are generally assumed to be benign our study shows that at a median age of 18 months almost half of the EV-infected infants (48.3%) and 20% of HPeV-positive infants presented some developmental concern in the ASQ-3 test. We recommend monitor the neurological development of infants during the first years of life after HPeV CNS infection and especially after EV CNS infection, even in mild cases, for an early intervention and stimulation of psychomotor development if necessary.
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In children aged <3 months, approximately 90% of those with HPeV-positive CSF and >50% of those with EV-positive CSF showed normal CSF cell counts, consistent with previous reports' results.
“In children aged <3 months, approximately 90% of those with HPeV-positive CSF and >50% of those with EV-positive CSF showed normal CSF cell counts, consistent with previous reports' results (21–25).”
From Epidemiology of pediatric meningitis and encephalitis in Japan: a cross-sectional study (2024) · cites this paper as [25]
The Results (page unavailable) report no CSF pleocytosis in HPeV-infected infants, supporting the claim that normal cell counts were common. They report pleocytosis in 50% of EV-positive patients, however, implying 50%—not more than 50%—without it; the HPeV figure is also 100%, rather than approximately 90%. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSepsis-like syndrome has been reported in 40-80% of HPeV (especially type 3) infections and 10-30% of EV infections in young infants.
“Sepsis-like syndrome has been reported in 40–80% of HPeV (especially type 3) infections and 10–30% of EV infections in young infants (21–27).”
From Epidemiology of pediatric meningitis and encephalitis in Japan: a cross-sectional study (2024) · cites this paper as [25]
The Results report clinical sepsis in 53.3% of HPeV-positive infants and 12.1% of EV-positive infants, values within the claimed ranges; Table 2 identifies 14 of 15 HPeV cases as type 3. But the study includes only infants younger than 90 days with CNS infection, so it does not establish those ranges for HPeV and EV infections in young infants generally. The copy has no page numbers for these passages. (LLM, conf=0.86)
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- Authors
- de Ceano-Vivas, M., García, M. L., Velázquez, A., Martín del Valle, F., Menasalvas, A., Cilla, A., Epalza, C., Romero, M. P., Cabrerizo, M., & Calvo, C.
- Affiliations
- Hospital Universitario La Paz (ES)
- Hospital Universitario Virgen de la Arrixaca (ES)
- Hospital Universitario de Burgos (ES)
- Hospital Universitario 12 De Octubre (ES)
- Instituto de Salud Carlos III (ES)
- Venue
- Frontiers in Pediatrics
- Publisher
- Frontiers Media SA
- Published
- 2021-09-28
- Volume
- 9
- Pages
- 719119-719119
- ISSN
- 2296-2360 (ISSN-L)
- PMC
- PMC8505960
- OpenAlex
- W3202241404
- Cited by
- 22
- References
- 41
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 10 · 2023: 4 · 2022: 1
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Pediatrics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Instituto de Salud Carlos III (PI18CIII/00017)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Literature Analysis and Criticism
- Keywords
- human parechovirus, central nervous system infection, neurodevelopmental outcomes, infants under 90 days, neurodevelopmental delay, communication development, motor development, ASQ-3, early intervention
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