Neurodevelopmental impairment is associated with altered white matter development in a cohort of school-aged children born very preterm

Abstract

Individuals born very preterm (<32 weeks gestation) have altered brain growth and white matter maturation relative to their full-term peers, and approximately 30% will experience neurodevelopmental impairment. We investigated the relationship between neurodevelopmental impairment and MRI measures of white matter microstructure and brain volume. Children born before 30 weeks' gestation or who had very low birthweight (< 1500 g) underwent neurodevelopmental assessment and MRI at age 7 years as part of the PIANO study, a New Zealand-based cohort study. Fractional anisotropy (FA) and diffusivity measures were derived from diffusion tensor imaging to index white matter microstructure. Volumes were derived from T1-weighted imaging. Neurodevelopmental impairment was defined as a score < 85 on the Wechsler Intelligence Scale for Children, <5th centile on the Movement Assessment Battery for Children or a diagnosis of cerebral palsy by a paediatrician. Relationships between MRI and neurodevelopmental impairment were assessed with general linear models adjusted for sex, gestational age at birth, birthweight z-score, age at assessment, New Zealand Deprivation index score and multiplicity. Children with neurodevelopmental impairment (n = 38) had smaller total brain, cortical grey matter and cerebral white matter volumes compared to children without neurodevelopmental impairment (n = 62) (p < 0.05, false discovery rate corrected), but the regional volume differences did not remain significant after adjustment for total brain volume. Lower FA and higher radial diffusivity were observed in the superior longitudinal fasciculi, uncinate fasciculi and right hemisphere corticospinal tract in children with neurodevelopmental impairment. This may reflect differences in cellular properties such as myelination or axonal packing. Neurodevelopmental impairment may reflect smaller overall brain volume and altered microstructure in white matter tracts that are important for language, cognitive and motor functioning.

Keywords: Brain volume; DTI; MRI; Myelination; Neurodevelopment; Preterm; White matter.

Fig. 1

Mean difference and 95% CI in fractional anisotropy (FA) between children with neurodevelopmental impairment (NDI) compared to children without NDI (reference). Solid lines/solid circles = left hemisphere; broken lines/open circles = right hemisphere; * = significant following false discovery rate correction. Fmajor = forceps major; fminor = forceps minor; ATR = anterior thalamic radiation; CAB = cingulum angular bundle; CCG = cingulum cingulate gyrus; ILF = inferior longitudinal fasciculus; SLF_p = superior longitudinal fasciculus parietal bundle; SLF_t = superior longitudinal fasciculus temporal bundle; UNC = uncinate fasciculus.

Fig. 2

Mean difference in mean diffusivity (MD) between children with neurodevelopmental impairment (NDI) compared to children without neurodevelopmental impairment. Solid lines/solid circles = left hemisphere; broken lines/open circles = right hemisphere; * = significant following false discovery rate correction. Fmajor = forceps major; fminor = forceps minor; ATR = anterior thalamic radiation; CAB = cingulum angular bundle; CCG = cingulum cingulate gyrus; ILF = inferior longitudinal fasciculus; SLF_p = superior longitudinal fasciculus parietal bundle; SLF_t = superior longitudinal fasciculus temporal bundle; UNC = uncinate fasciculus.

Fig. 3

Mean difference in radial diffusivity (RD) between with neurodevelopmental impairment (NDI) compared to children without neurodevelopmental impairment. Solid lines/solid circles = left hemisphere; broken lines/open circles = right hemisphere; * = significant following false discovery rate correction. Fmajor = forceps major; fminor = forceps minor; ATR = anterior thalamic radiation; CAB = cingulum angular bundle; CCG = cingulum cingulate gyrus; ILF = inferior longitudinal fasciculus; SLF_p = superior longitudinal fasciculus parietal bundle; SLF_t = superior longitudinal fasciculus temporal bundle; UNC = uncinate fasciculus.

Fig. 4

Mean difference in axial diffusivity (AD) between children with neurodevelopmental impairment (NDI) compared to children without neurodevelopmental impairment. Solid lines/solid circles = left hemisphere; broken lines/open circles = right hemisphere. Fmajor = forceps major; fminor = forceps minor; ATR = anterior thalamic radiation; CAB = cingulum angular bundle; CCG = cingulum cingulate gyrus; ILF = inferior longitudinal fasciculus; SLF_p = superior longitudinal fasciculus parietal bundle; SLF_t = superior longitudinal fasciculus temporal bundle; UNC = uncinate fasciculus.