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Human parechovirus meningitis and gross-motor neurodevelopment in young children

  • Ted M. T. van HinsberghEmail author
  • Stephanie C. M. de Crom
  • Robert Lindeboom
  • Marceline A. M. van Furth
  • Charlie C. Obihara
Original Article

Abstract

This multicenter prospective cohort study describes the impact of human parechovirus meningitis on gross-motor neurodevelopment of young children. Gross-motor function was measured using Alberta Infant Motor Scale. Of a total of 38 eligible children < 10 months of age at onset, nine cases had clinical evidence of meningitis and polymerase chain reaction positive for human parechovirus in cerebrospinal fluid; 11 had no meningitis and polymerase chain reaction positive for human parechovirus in nasopharyngeal aspirate, blood, urine, or feces; and in 18, no pathogen was identified (reference group).

The children with human parechovirus meningitis showed more frequent albeit not statistically significant suspect gross-motor function delay (mean Z-score (standard deviation) − 1.69 (1.05)) than children with human parechovirus infection-elsewhere (− 1.38 (1.51)). The reference group did not fall in the range of suspect gross-motor function delay (− 0.96 (1.07)). Adjustment for age at onset and maternal education did not alter the results.

Conclusion: Six months after infection, children with human parechovirus meningitis showed more frequent albeit not statistically significant suspect gross-motor function delay compared to the population norm and other two groups. Longitudinal studies in larger samples and longer follow-up periods are needed to confirm the impact and persistence of human parechovirus meningitis on neurodevelopment in young children.

What is Known:

• Human parechovirus is progressively becoming a major viral cause of meningitis in children.

• There is keen interest in the development of affected infants with human parechovirus meningitis.

What is New:

• This study describes prospectively gross-motor functional delay in children with both clinical evidence of meningitis and polymerase chain reaction positive for human parechovirus in cerebrospinal fluid.

• It shows the importance of screening young children for developmental delay in order to refer those with delay for early intervention to maximize their developmental potential.

Keywords

Human parechovirus Meningitis Children Neurodevelopment 

Abbreviations

AIMS

Alberta Infant Motor Scale

CI

Confidence interval

CNS

Central nervous system

CP

Cerebral palsy

CSF

Cerebrospinal fluid

EV

Enterovirus

GMF

Gross-motor function

HPeV

Human parechovirus

n

Number

NPA

Nasopharyngeal aspirate

RT-qPCR

Reverse transcriptase real-time quantitative polymerase chain reaction

SD

Standard deviation of the mean

T0

Presenting at emergency or outpatient departments of the participating hospitals

T6

Follow-up 6 months after visiting the emergency or outpatient departments of the participating hospitals

Notes

Acknowledgements

We thank all children and their parents/legal guardians; pediatricians; nurses in St. Elisabeth, Tweesteden, and Amphia Hospital for participating in this study; Mrs. C.A.M. Smid for her work as study-secretary; and Mrs. N. Hmimsa for her work as planning-secretary.

Definitions

HPeV-meningitis: children with clinical evidence of meningitis and RT-qPCR positive for HPeV in CSF

HPeV-infection-elsewhere: children with no clinical evidence of meningitis and RT-qPCR HPeV-positive in nasopharyngeal aspirate swab, blood, urine, or feces

Reference: children with no clinical evidence of meningitis and in whom no pathogen was identified

No show: did not show after 3× reminded

Lost to follow-up: moved to another address, changed telephone number, parents too busy to come

Authors’ contributions

Mrs. van Hinsbergh, MSc., conceptualized and designed the follow-up study. She was responsible for the data collection, carried out the initial statistical analyses, drafted the initial manuscript, revised the manuscript, and approved the final manuscript.

Dr. R. Lindeboom interpreted the statistical data, reviewed the manuscript, and approved the final manuscript.

Prof. Dr. van Furth, Dr. de Crom, and Dr. Obihara conceptualized and designed the study, interpreted the data, reviewed the manuscript, and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

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

Ethical 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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PediatricsElisabeth-Tweesteden HospitalTilburgthe Netherlands
  2. 2.Department of PediatricBravis HospitalBergen op Zoomthe Netherlands
  3. 3.Department of Clinical Epidemiology, Biostatistics and BioinformaticsAmsterdam UMC, Academic Medical CenterAmsterdamthe Netherlands
  4. 4.Department of Pediatric Infectious Diseases and ImmunologyAmsterdam UMC, Vrije Universiteit AmsterdamAmsterdamthe Netherlands

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