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Neurodevelopmental outcomes of newborns and infants with parechovirus and enterovirus central nervous infection: a 5-year longitudinal study

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Abstract

Though parechovirus (PeV) and enterovirus (EV) are common causes of central nervous system (CNS) infection in childhood, little is known about their long-term neurologic/neurodevelopmental complications. We investigated, longitudinally over a 5-year period, motor neurodevelopment in term-born newborns and infants with RT-qPCR-confirmed PeV- or EV-CNS infection. Motor neurodevelopment was assessed with standardized tests: Alberta Infant Motor Scale (AIMS), Bayley Scales of Infant and Toddler Development version-3 (Bayley-3-NL), and Movement Assessment Battery for Children version-2 (M-ABC-2-NL) at 6, 12, 24, and 60 months post-infection. Results of children with PeV-CNS infection were compared with those of peers with EV-CNS infection and with Dutch norm references. In the multivariate analyses adjustments were made for age at onset, gender, maternal education, and time from CNS infection Sixty of 172 eligible children aged ≤ 3 months were included. Children with PeV-CNS infection had consistently lower, non-significant mean gross motor function (GMF) Z-scores, compared with peers with EV-CNS infection and population norm-referenced GMF. Their GMF improved between 6 and 24 months and decreased at 5 years. Their fine motor function (FMF) scores fell within the population norm reference.

Conclusion: These results suggest that the impact of PeV-A3-CNS infection on gross motor neurodevelopment in young children might manifest later in life. They highlight the importance of longitudinal neurodevelopmental assessments of children with PeV-A3-CNS infection up to school age.

What is Known:

• Human parechovirus (PeV) is a major cause of central nervous system infection (CNS infection) in newborns and infants.

• There is interest in the neurological and neurodevelopmental outcome of newborns and infants with PeV-A3-CNS infection.

What is New:

• This prospective study compares the motor neurodevelopment of term-born newborns and infants with PeV-A3-CNS infection with those with EV-CNS infection and with norm references.

• The results support the importance of follow-up of newborns and infants with PeV-A3-CNS infection to detect subtle neurodevelopmental delay and start early interventions.

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Abbreviations

AIMS:

Alberta Infant Motor Scale

Bayley-3-NL:

Bayley Scales of Infant and Toddler Development version-3

β :

Unstandardized regression coefficient beta

CI:

Confidence interval

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

EV:

Enterovirus

FMF:

Fine motor function neurodevelopment

GMF:

Gross motor function neurodevelopment

M-ABC-2-NL:

Movement Assessment Battery for Children version-2

n :

Number of children attending follow-up visit

NMLE:

Package Linear and Nonlinear Mixed-Effect Models

PeV:

Parechovirus

RT-qPCR:

Real-time quantitative polymerase chain reaction

SD:

Standard deviation of the mean

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Acknowledgements

The authors thank all children and their parents and/or legal guardians, pediatricians, nurses in Elisabeth Hospital, Tweesteden Hospital, and Amphia Hospital for participating in this study; Mrs. S.C.M de Crom, MD, PhD for her work conceptualizing and designing the epidemiologic study; Mrs. E.J.M. Veldkamp, MD for her efforts during the inclusion phase; Mrs. C.A.M. Smid for her work as a study-secretary; and Mrs. N. Hmimsa, for her work as a planning-secretary. We are deeply indebted to late Dr. Marcel Peters, Microbiologist, one of the initiators of this research project.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Elisabeth-Tweesteden Hospital, Hilvarenbeekseweg 60, Tilburg, 5022 LC, The Netherlands

    Ted van Hinsbergh & Charlie Obihara

  2. Amsterdam UMC, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Medical Faculty (AMC), University of Amsterdam, Amsterdam, The Netherlands

    Roy-G. Elbers

  3. Department of Medical Psychology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands

    Zita Bouman

  4. Department of Paediatric Infectious Diseases and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, AI&II, De Boelelaan 1117, Amsterdam, The Netherlands

    Marceline van Furth

Authors
  1. Ted van Hinsbergh
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  4. Marceline van Furth
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  5. Charlie Obihara
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Contributions

Dr. van Hinsbergh conceptualized and designed the follow-up study. She was responsible for the data collection, carried out the statistical analyses, drafted the initial manuscript, revised the manuscript, and approved the final manuscript. Dr. Elbers and Dr. Bouman interpreted the statistical data, reviewed the manuscript, and approved the final manuscript. Prof. Dr. Van Furth and Dr. Obihara conceptualized and designed the study, interpreted the data, reviewed the manuscript, and approved the final manuscript.

Corresponding author

Correspondence to Ted van Hinsbergh.

Ethics declarations

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved of by the medical ethics committee of each participating center (NL-21361.008.07). This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Yes we consent for publication.

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The authors declare no competing interests.

Additional information

Communicated by Gregorio Paolo Milani

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van Hinsbergh, T., Elbers, RG., Bouman, Z. et al. Neurodevelopmental outcomes of newborns and infants with parechovirus and enterovirus central nervous infection: a 5-year longitudinal study. Eur J Pediatr 181, 2005–2016 (2022). https://doi.org/10.1007/s00431-022-04402-1

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  • DOI: https://doi.org/10.1007/s00431-022-04402-1

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