Neonatal Critical Illness, 8-Year White Matter Microstructure, and Motor Function in Children Born Very Preterm.

OBJECTIVE

To assess relationships between neonatal critical illness in children born preterm with white matter maturation and clinical motor and visual-motor integration (VMI) performance at 8 years.

STUDY DESIGN

Prospective longitudinal study of 234 neonates (24-32 weeks gestational age [GA]) recruited from 2006 to 2013 at a tertiary neonatal intensive care unit. Neonatal critical illness included infection, bronchopulmonary dysplasia, retinopathy of prematurity, severe intraventricular hemorrhage, and significant white matter injury. At age 8 years, children completed visual-motor (Beery-Buktenica Developmental Test of Visual-Motor Integration, sixth edition) and motor (Movement Assessment Battery for Children, second edition) assessments. Tract-based spatial statistics were used to analyze fractional anisotropy from diffusion tensor imaging acquired at 8 years to measure white matter maturation.

RESULTS

Of 226 survivors, 129 children (69 males [53%]) were assessed at 8 years and had high-quality diffusion tensor imaging. Neonatal critical illness counts ≥ 3 were associated with 11.8-point decrease in motor (CI -23-(-.55), P = .04) and 11.3-point decrease in VMI scores (CI -18.2-(-4.5), P = .001), accounting for GA and maternal education. Higher neonatal critical illness counts (P = .04) and lower motor (P < .001) and VMI (P = .04) scores were related to bilateral reductions in white matter fractional anisotropy in the corpus callosum and motor association pathways, accounting for GA, neonatal brain injury, maternal education, and age at scan.

CONCLUSIONS

Cumulative critical illness in neonates born preterm is associated with long-term changes in white matter microstructure and maturation, which are related to motor and visual motor performance at school-age. These findings highlight the long-term importance of neonatal intensive care exposures and need for school-age follow-up of children born preterm.