White matter microstructure and cognitive outcomes in relation to neonatal inflammation in 6-year-old children born preterm

BACKGROUND: Cognitive outcomes in preterm (PT) children have been associated with microstructural properties of white matter. PT children who experienced neonatal inflammatory conditions have poorer cognitive outcomes than those who did not. The goal of this study was to contrast white matter microstructure and cognitive outcomes after preterm birth in relation to the presence or absence of severe inflammatory conditions in the neonatal period. METHODS: PT children (n = 35), born at gestational age 22–32 weeks, were classified as either PT+ (n = 12) based on a neonatal history of inflammatory conditions, including bronchopulmonary dysplasia, necrotizing enterocolitis or culture positive sepsis, or PT- (n = 23) based on the absence of the three inflammatory conditions. Full term (FT) children (n = 43) served as controls. Participants underwent diffusion MRI and cognitive testing (intelligence, reading, and executive function) at age 6 years. The corpus callosum was segmented into 7 regions using deterministic tractography and based on the cortical projection zones of the callosal fibers. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for each segment. General linear models with planned contrasts assessed group differences in FA, MD and cognitive outcomes. Pearson correlations assessed associations of white matter metrics and cognitive outcome measures. RESULTS: FA was significantly lower and MD was significantly higher in PT+ compared to PT- or FT groups in multiple callosal segments, even after adjusting for gestational age. Executive function scores, but not intelligence or reading scores, were less favorable in PT+ than in PT- groups. Among the entire sample, occipital FA was significantly correlated with IQ (r = 0.25, p < 0.05), reading (r = 0.32, p < 0.01), and executive function (r = −0.28, p < 0.05) measures. Anterior frontal FA and superior parietal FA were significantly correlated with executive function (r = −0.25, r = 0.23, respectively, p < 0.05). CONCLUSIONS: We observed differences in the white matter microstructure of the corpus callosum and in the cognitive skills of 6-year-old PT children based on their history of neonatal inflammation. Neonatal inflammation is one medical factor that may contribute to variation in long-term neurobiological and neuropsychological outcomes in PT samples.