Parechovirus central nervous system infection in neonates and young children: A 5-year follow-up

Summary In this thesis, we present various studies that provide insight into the adverse neurologic and neurodevelopmental outcomes of children with parechovirus central nervous system infection (PeV-CNS-infection) in the first 5 years after the infection. There is a paucity of cohort studies that have prospectively evaluated short- and long-term neurodevelopmental outcome in children with PeV-CNS-infection. We discuss and provide suggestions for follow-up. PART 1. General Introduction Chapter 1 encloses a general introduction of this thesis, in which the aims and outlines are described. We give an introductory overview on PeV-CNS-infection in neonates and young children. PART 2. Literature search Parechovirus CNS-infection and neurologic and neurodevelopmental outcome In Chapter 2, we present a systematic review and meta-analyses of neurodevelopmental outcomes in neonates and young children with PeV-CNS-infection. The primary outcomes are neurologic sequelae, impairment in visual and auditory functions, and GMF-neurodevelopmental delay. The secondary outcomes are signs of late neurodevelopmental delay such as FMF-neurodevelopmental delay, cognitive impairment, behavioural- and emotional problems and speech- and language delay. With this systematic review, we attempted to close the information gap for clinicians and neurodevelopmentalists, on existing literature by conducting a meta-analysis. We hope this will provide a scientific basis to plan frequency and duration of follow-up visits, as well as strategies to mitigate potentially evolving sequelae and neurodevelopmental delay after PeV-CNS-infection. PART 3. Cross sectional assessment and assignment to subgroups Chapter 3 focuses on recruitment, diagnosis, inclusion and exclusion criteria, assignment to subgroups and GMF-neurodevelopmental outcome, 6 months after the infection or suspected infection. We compared the group of children with PeV-CNS-infection with an age of onset ≤ 10 months with peers with a PeV-infection-elsewhere in the body and with peers from the reference group. We tested the GMF-neurodevelopment with the AIMS. The group of children with a PeV-CNS-infection showed a clinically relevant GMF-neurodevelopmental delay compared to the reference group and a suspected GMF-neurodevelopmental delay compared to the population standard norm. Chapter 4 presents a study in which we compared the GMF- and FMF-neurodevelopmental outcomes in children with an age of onset of 2 days to 12.8 years in subgroups of children with a PeV- and an EV-CNS-infection, PeV- and an EV-infection-elsewhere in the body and a reference group. We tested the GMF- and FMF-neurodevelopment with the BSID-III and the M-ABC-2-NL. We found no statistically significant differences in mean performance GMF- and/or FMF-neurodevelopment and in the number of children with suspected delay in GMF- and/or FMF-neurodevelopment between the PeV- or EV-infected and non-infected children. PART 4. Longitudinal assessment. The impact of PeV-CNS-infection on gross and fine motor function neurodevelopment Chapters 5 describes the longitudinal impact of PeV-CNS-infection on GMF-neurodevelopment in neonates and young children. We compared the group of children with PeV-CNS-infection and an age of onset ≤ 24 months with peers from the reference group. The PeV-CNS-infection was serially tested at 6, 12 and 24 months follow-up with the AIMS, the Bayley-3-NL and the M-ABC-2 NL. Chapter 6 presents the longitudinal impact of PeV-CNS-infection on GMF- and FMF-neurodevelopment in neonates. We compared the group of children with a PeV-CNS-infection with an age of onset ≤ 3 months to peers with an EV-CNS-infection. The GMF-neurodevelopment was serially tested with the AIMS, the Bayley-3-NL and the M-ABC-2-NL at 6, 12 and 24 months and 5 years follow-up. The FMF-neurodevelopment was tested with the Bayley-3-NL and the M-ABC-2-NL at 24 months and 5 years follow-up. PART 5. General discussion and summary Chapter 7 contains the general discussion with the conclusions and recommendations of this thesis and Chapter 8 the English and Dutch summary.