Medical Student Stanford University School of Medicine Everett, Washington, United States
Background: Infants born very preterm (VPT: < 32 weeks gestational age, GA) are at increased risk of abnormal white matter development and long-term neurocognitive impairments. Inflammation during the early neonatal period may alter white matter pathway development in the vulnerable VPT brain. While microstructural differences in the corpus callosum have been observed at age 6 in VPT children with a history of severe neonatal inflammation, white matter differences related to inflammation during the neonatal period remain understudied. Objective: To contrast white matter microstructure of the corpus callosum (CC) and cingulum in VPT infants based on neonatal inflammation status using near-term diffusion magnetic resonance imaging (dMRI). Design/Methods: We performed a retrospective cohort study of VPT infants (n=154) born at GA 22-32 weeks between March 2016 to March 2020. Infants were grouped based on the presence (I+) or absence (I-) of >= 1 major neonatal inflammatory condition (bronchopulmonary dysplasia, necrotizing enterocolitis, or sepsis). Per standard of care, all infants underwent an MRI brain scan at 34-45 weeks post menstrual age (PMA), including dMRI. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for 7 segments of the CC and left and right cingulum tracts. Group differences were analyzed using analysis of covariance (ANCOVA), controlling for PMA at scan. Due to imbalance of GA in the full sample, secondary ANCOVA analyses were performed in a GA-matched subset (n=28) to isolate the effect of inflammation. Results: Table 1 summarizes group characteristics and Table 2 summarizes results of group comparisons for white matter metrics in both the full (n=154) and GA-matched sample (n=28). Compared to the I- group, infants in the I+ group had significantly lower mean FA in the superior frontal, occipital, and temporal segments of the CC, and in both cingulum tracts. No significant differences were observed for MD in any tract. In the GA-matched sample (n=28), the I+ group demonstrated reduced FA in 7 of 9 tracts compared to the I- group; differences in FA of the temporal CC segment were significantly different (F=5.65, p=0.03, η2= 0.26).
Conclusion(s): VPT infants with neonatal inflammation had lower FA in multiple segments of the CC and cingulum bilaterally, a pattern that held when matching for GA at birth. These findings suggest that alterations in white matter development related to inflammation begin in the neonatal period. On-going analysis will explore relations between neonatal inflammation, white matter microstructure, and early neurodevelopmental outcomes.