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Combining advanced MRI and EEG techniques better explains long-term motor outcome after very preterm birth

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Abstract

Background

Preterm born children are at high risk for adverse motor neurodevelopment. The aim of this study was to establish the relationship between motor outcome and advanced magnetic resonance imaging (MRI) and electroencephalography (EEG) measures.

Methods

In a prospective cohort study of 64 very preterm born children, the motor outcome was assessed at 9.83 (SD 0.70) years. Volumetric MRI, diffusion tensor imaging (DTI), and EEG were acquired at 10.85 (SD 0.49) years. We investigated associations between motor outcome and brain volumes (white matter, deep gray matter, cerebellum, and ventricles), white matter integrity (fractional anisotropy and mean, axial and radial diffusivity), and brain activity (upper alpha (A2) functional connectivity and relative A2 power). The independence of associations with motor outcome was investigated with a final model. For each technique, the measure with the strongest association was selected to avoid multicollinearity.

Results

Ventricular volume, radial diffusivity, mean diffusivity, relative A2 power, and A2 functional connectivity were significantly correlated to motor outcome. The final model showed that ventricular volume and relative A2 power were independently associated with motor outcome (B = −9.42 × 10−5, p = 0.027 and B = 28.9, p = 0.007, respectively).

Conclusions

This study suggests that a lasting interplay exists between brain structure and function that might underlie motor outcome at school age.

Impact

  • This is the first study that investigates the relationships between motor outcome and brain volumes, DTI, and brain function in preterm born children at school age.

  • Ventricular volume and relative upper alpha power on EEG have an independent relation with motor outcome in preterm born children at school age.

  • This suggests that there is a lasting interplay between structure and function that underlies adverse motor outcome.

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Fig. 1: Study flow chart.
Fig. 2: T1 MR images and lower and upper alpha power spectra (8–10 and 10–13 Hz, respectively) of two representative cases.
Fig. 3: Scatterplots of associations between motor outcome and multiple neuromodalities.

Change history

  • 25 June 2021

    The name of the the first author was corrected.

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Acknowledgements

The Department of Neonatology received a grant from Chiesi Pharmaceuticals B.V. Schiphol, The Netherlands for the execution of this study. We wish to thank R.J.M. Berkhout for her assistance during the data collection of the study. We would also like to thank all the technicians of the laboratory of the Clinical Neurophysiology and Radiology Department of the Leiden University Medical Center. We thank J. Lak and R. van Leeuwen for the assistance with the acquisition of the EEG and MRI data and the guidance of the patients and their parents, and Prof. Dr. Linda de Vries for carefully reviewing the current manuscript. All authors meet the authorship requirements. S.J.S. received a grant from Chiesi Pharmaceuticals B.V. Schiphol, The Netherlands for the execution of this study. Chiesi Pharmaceuticals B.V. was not involved in the conduct of the research.

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Contributions

C.v.W.: conceptualization, methodology, formal analysis, investigation, writing—original draft, visualization; S.J.S.: conceptualization, data acquisition, methodology, writing—review and editing, supervision, project administration, funding acquisition; L.J.: conceptualization, methodology, writing—review and editing, project administration; A.A.v.d.B.-H.: conceptualization, methodology, formal analysis, investigation, data curation, writing—review and editing L.A.v.d.P.: writing—review and editing, supervision; F.T.W.-d.B.: conceptualization, data acquisition, methodology, writing—review & editing; C.J.S.: software, writing—review and editing, supervision; C.M.P.C.D.P.-S.: conceptualization, data acquisition, methodology, writing—review and editing, supervision, project administration.

Corresponding author

Correspondence to Charlotte van ’t Westende.

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Competing interests

C.M.P.C.D.P.-S. is founder and consultant at Neurophyxia BV. She holds several patents and stocks of Neurophyxia BV. None of this work has a relationship with the current manuscript. The other authors declare no competing interests.

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Written consent was obtained from both parents, and all children received age-specific information about the study.

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van ’t Westende, C., Steggerda, S.J., Jansen, L. et al. Combining advanced MRI and EEG techniques better explains long-term motor outcome after very preterm birth. Pediatr Res (2021). https://doi.org/10.1038/s41390-021-01571-x

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