Functional Connectivity Relationships to Longitudinal Motor Outcomes Differ in Very Preterm Children With and Without
Peppar E P Cyr1, Rachel E Lean1, Jeanette K Kenley1
1Departments of Neurology (PEPC, JKK, SK, DM, JJN, DA, RGB, CDS), and Psychiatry (REL, CER), Washington University School of Medicine; Mallinckrodt Institute of Radiology (JSS, CDS); Department of Psychology (TLR), Washington University in St. Louis; and Department of Pediatrics (CER, CDS), Washington University School of Medicine, St. Louis, MO.
Insights
Functional connectivity (FC) in very preterm (VPT) infants predicts motor outcomes. Neonatal FC disruptions in uninjured VPT children may lead to later motor deficits not apparent at age 2.
Area of Science:
- Neuroscience
- Developmental Pediatrics
- Medical Imaging
Background:
- Very preterm (VPT) infants face high risks of motor disabilities.
- Early identification of motor deficits in VPT children is challenging, particularly for those developing issues later in childhood.
- Functional connectivity (FC) MRI offers a potential tool for early assessment.
Purpose of the Study:
- To investigate the relationship between functional connectivity (FC) measured at term-equivalent age and motor outcomes at 2 and 5 years in very preterm (VPT) children.
- To identify early neural markers for motor development in VPT infants, with or without brain injury.
Main Methods:
- A longitudinal observational cohort study involving VPT infants (gestational age ≤30 weeks).
- Functional connectivity (FC) MRI was performed at term-equivalent age.
- Motor development was assessed at 2 and 5 years using standardized scales (Bayley Scales and Movement Assessment Battery for Children).
- Statistical models examined the association between FC measures and motor outcomes, considering brain injury status.
Main Results:
- In VPT children with brain injury, reduced left-right motor cortex FC correlated with increased odds of fine motor task inability at age 5.
- In uninjured VPT children, altered basal ganglia-motor cortex FC was linked to poorer fine motor skills, and cerebellum-motor cortex FC to poorer balance and fine motor skills at age 5.
- These motor deficits in uninjured children emerged by age 5, despite normal 2-year assessments.
Conclusions:
- Neonatal FC can predict motor deficits in VPT children, both with and without brain injury.
- Motor planning and coordination difficulties in uninjured VPT children may stem from early neural disruptions, becoming apparent later in development.
- Continuous motor monitoring is recommended for VPT children, as 2-year assessments may miss milder deficits. FC at term-equivalent age shows promise for early disability prediction.
Background And Objectives:
Children born very preterm (VPT) have high rates of motor disability, but mechanisms for early identification remain limited, especially for children who fall behind in early childhood. This study examines the relationship between functional connectivity (FC) measured at term-equivalent age and motor outcomes at 2 and 5 years.
Methods:
In this longitudinal observational cohort study, VPT children (gestational age 30 weeks and younger) with and without high-grade brain injury underwent FC MRI at term-equivalent age. Motor development was assessed using the Bayley Scales of Infant Development, Third Edition, at corrected age 2 years and Movement Assessment Battery for Children, Second Edition, at age 5 years. Logistic and negative binomial/Poisson regression models examined relationships between FC measures and 5-year task scores, with and without 2-year scores as covariates. Infants were categorized as "injured" or "uninjured" based on structural MRI findings at term-equivalent age.
Results:
In the injured group (n = 34), each 1 SD decrease in neonatal left-right motor cortex FC was related to approximately 4× increased odds of being unable to complete a fine motor task at age 5 (log odds = -1.34, p < 0.05). In the uninjured group (n = 41), stronger basal ganglia-motor cortex FC was related to poorer fine motor scores (Est = -0.40, p < 0.05) and stronger cerebellum-motor cortex FC was related to poorer balance and fine motor scores (Est = -0.05 to -0.23, p < 0.05), with balance persisting with adjustment for 2-year scores.
Discussion:
In VPT children with brain injury, interhemispheric motor cortex FC was related to motor deficits at 5-year assessment, similar to previous findings at 2 years. In uninjured children, FC-measured disruption of the motor system during the neonatal period was associated with motor planning/coordination difficulties that were not apparent on 2-year assessment but emerged at 5 years, suggesting that the neural basis of these deficits was established very early in life. Subsequently, 2-year follow-up may not be sufficient to detect milder motor deficits in VPT children, and they should be monitored for motor difficulties throughout the preschool years. For all VPT children, FC at term-equivalent age has the potential to improve our ability to predict disability before it presents behaviorally.
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