Altered structural brain networks at term-equivalent age in preterm infants with grade 1 intraventricular hemorrhage

Abstract

Background: Preterm infants are at risk for structural disruption of brain connectivity due to perinatal complications encountered during the fetal and neonatal periods. This study aimed to investigate the development of connectivity using diffusion tensor imaging at near-term age and the effect of grade 1 intraventricular hemorrhage on it.

Methods: A total of 86 infants (55 preterm infants, 24 full-term infants) without apparent brain injury underwent diffusion magnetic resonance imaging (MRI) between 36 and 41 weeks post-menstrual age. The diffusion-MRI based connectomics were constructed from 64-segmented regions by using the Johns Hopkins University neonate atlas and were weighted with fractional anisotropy. The connectomes were quantified in the structural networks and investigated using network metrics, such as the clustering coefficient, local efficiency, characteristic path length, global efficiency, and small-worldness. We compared the differences in the brain networks of preterm infants with or without grade 1 intraventricular hemorrhage in binary and fractional anisotropy-weighted (wFA) connectomes.

Results: The 55 preterm infants had a mean gestational age at birth of 29.3 +/- 4.1 weeks and the 24 term-born infants, 38.1 +/- 1.1 weeks. A total of 13 of the 55 preterm infants (23.6%) were diagnosed with grade 1 intraventricular hemorrhage. The development of connectivity of the brain network in preterm infants without intraventricular hemorrhage was comparable at near-term age to that in term infants. The preterm infants with germinal matrix hemorrhage exhibited higher clustering (0.093 +/- 0.015 vs. 0.088 +/- 0.007, p = 0.027) and local efficiency (0.151 +/- 0.022 vs. 0.141 +/- 0.010, p = 0.025), implying the potential for segregation. However, the preterm infants with intraventricular hemorrhage revealed a longer path length (0.291 +/- 0.035 vs. 0.275 +/- 0.019, p = 0.020) and lower global efficiency (3.998 +/- 0.473 vs. 4.212 +/- 0.281, p = 0.048), indicating a decreased integration in the wFA connectivity matrix than those without germinal matrix hemorrhage, after correcting for gestational age, sex, bronchopulmonary dysplasia, and age at scan.

Conclusion: Grade 1 intraventricular hemorrhage in preterm infants may enhance the capacity for local information transfer and the relative reinforcement of the segregation of networks at the expense of global integration capacity.