Abstract
We aim to investigate early developmental trajectories of the autonomic nervous system (ANS) as indexed by the pupillary light reflex (PLR) in infants with (i.e. preterm birth, feeding difficulties, or siblings of children with autism spectrum disorder) and without (controls) increased likelihood for atypical ANS development. We used eye-tracking to capture the PLR in 216 infants in a longitudinal follow-up study spanning 5 to 24 months of age, and linear mixed models to investigate effects of age and group on three PLR parameters: baseline pupil diameter, latency to constriction and relative constriction amplitude. An increase with age was found in baseline pupil diameter (F(3,273.21) = 13.15, p < 0.001, \({\eta }_{\mathrm{p}}^{2}\) = 0.13), latency to constriction (F(3,326.41) = 3.84, p = 0.010, \({\eta }_{\mathrm{p}}^{2}\) = 0.03) and relative constriction amplitude(F(3,282.53) = 3.70, p = 0.012, \({\eta }_{p}^{2}\) = 0.04). Group differences were found for baseline pupil diameter (F(3,235.91) = 9.40, p < 0.001, \({\eta }_{\mathrm{p}}^{2}\) = 0.11), with larger diameter in preterms and siblings than in controls, and for latency to constriction (F(3,237.10) = 3.48, p = 0.017, \({\eta }_{\mathrm{p}}^{2}\) = 0.04), with preterms having a longer latency than controls. The results align with previous evidence, with development over time that could be explained by ANS maturation. To better understand the cause of the group differences, further research in a larger sample is necessary, combining pupillometry with other measures to further validate its value.





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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We thank the parents and infants taking part in the TIARA study for their participation. We also thank our colleagues and students within the TIARA-team that helped with data collection. We also thank Geert Verbeke for statistical advice. Scripts for presentation of eye-tracking stimuli were provided by Luke Mason and Emily Jones of Birkbeck University. The stimulus presentation scripts were supported by awards from the Medical Research Council (MR/K021389/1; MR/T003057/1, EJ, MHJ, TC), and the EU-AIMS and AIMS-2-TRIALS programmes funded by the Innovative Medicines Initiative (IMI) Joint Undertaking Grant nos. 115300 (MHJ, TC) and no. 777394 (MHJ, EJHJ and TC; European Union’s FP7 and Horizon 2020, respectively). This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme, with in-kind contributions from the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies and funding from Autism Speaks, Autistica and SFARI. Any views expressed are those of the author(s) and not necessarily those of the funders.
TIARA Team: Lyssa M. de Vries, Center for Developmental Psychiatry, Department of Neurosciences, KU Leuven, Leuven, Belgium; University Hospital Leuven, Leuven, Belgium; Leuven Autism Research (LAuRes), KU Leuven, Leuven, Belgium. Lotte van Esch, Leuven Autism Research (LAuRes), KU Leuven, Leuven, Belgium; Parenting and Special Education Research Unit, Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, Belgium. Thijs Van Lierde, RIDDL Lab, Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium. Floor Moerman, RIDDL Lab, Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium. Maide Erdogan, RIDDL Lab, Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium. Melinda Mađarević, Leuven Autism Research (LAuRes), KU Leuven, Leuven, Belgium; Parenting and Special Education Research Unit, Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, Belgium. Julie Segers, Leuven Autism Research (LAuRes), KU Leuven, Leuven, Belgium; Parenting and Special Education Research Unit, Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, Belgium. Petra Warreyn, RIDDL Lab, Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium. Herbert Roeyers, RIDDL Lab, Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium. Ilse Noens, Leuven Autism Research (LAuRes), KU Leuven, Leuven, Belgium; Parenting and Special Education Research Unit, Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, Belgium. Gunnar Naulaers, University Hospital Leuven, Leuven, Belgium; Woman and Child, Department of Development and Regeneration, KU Leuven, Belgium. Bart Boets, Center for Developmental Psychiatry, Department of Neurosciences, KU Leuven, Leuven, Belgium; Leuven Autism Research (LAuRes), KU Leuven, Leuven, Belgium. Jean Steyaert, Center for Developmental Psychiatry, Department of Neurosciences, KU Leuven, Leuven, Belgium; University Hospital Leuven, Leuven, Belgium; Leuven Autism Research (LAuRes), KU Leuven, Leuven, Belgium.
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This work was supported by a project grant from the Fund for Scientific Research Flanders for the TIARA study (S001517N) and two grants from the Support Fund M.M. Delacroix (GV/B-319 and GV/B-375).
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LDV: conceptualization, methodology, data collection, data analysis, writing—original draft, review and editing; SA and TVL: data collection, writing—review and editing; PN: methodology, software, assistance in data analysis, writing—review and editing; LVE: project administration, writing—review and editing; PW and HR and IN: conceptualization, funding acquisition, writing—review and editing; BB: conceptualization, resources, supervision, writing—review and editing; GN and JS: conceptualization, supervision, funding acquisition, writing—review and editing. All authors read and approved the final version of the manuscript.
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de Vries, L.M., Amelynck, S., Nyström, P. et al. Investigating the development of the autonomic nervous system in infancy through pupillometry. J Neural Transm 130, 723–734 (2023). https://doi.org/10.1007/s00702-023-02616-7
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DOI: https://doi.org/10.1007/s00702-023-02616-7