Uncomplicated intraventricular hemorrhage is followed by reduced cortical volume at near-term age

Abstract

Background: Intraventricular hemorrhage (IVH) is the most common brain injury among premature infants. Neonates with IVH are at greater risk of impaired neurodevelopmental outcomes, compared with those without IVH. IVH causes destruction of the germinal matrix and glial precursor cells, with possible effects on cortical development.

Objective: To investigate cortical development after uncomplicated IVH (with no parenchymal involvement and no posthemorrhagic hydrocephalus). We hypothesized that uncomplicated IVH would be followed by reduced cortical volume among premature infants at near-term age.

Methods: A prospective cohort study was conducted, with preset selection criteria. Infants with small-for-gestational age birth weight, congenital abnormalities or brain malformations, metabolic disorders, recurrent sepsis, or necrotizing enterocolitis were excluded. Also, infants with posthemorrhagic hydrocephalus, parenchymal involvement of hemorrhage, cystic periventricular leukomalacia, or persistent ventriculomegaly were excluded, on the basis of routine serial ultrasonographic assessments. Three-dimensional images were acquired for 23 infants at near-term age, with 3-T magnetic resonance imaging and a magnetization-prepared rapid gradient echo sequence. Image analysis and segmentation of the cerebrum in different tissue types were based on signal contrast and anatomic localization. The cortical gray matter (CGM), subcortical gray matter, white matter, and intraventricular cerebrospinal fluid volumes of 12 infants with uncomplicated IVH were compared with those of 11 infants without IVH, using multivariate analysis of variance.

Results: The multivariate analysis of variance for the regional brain volumes in the 2 groups indicated significance (Wilks' lambda = 0.546). The CGM volume was significantly reduced in the IVH group (no-IVH group: 122 +/- 12.9 mL; IVH group: 102 +/- 14.6 mL; F = 13.218). This finding remained significant after testing for possible confounding factors and adjustment for size differences between the infants (F = 9.415). There was no difference in the volumes of subcortical gray matter, white matter, and cerebrospinal fluid.

Conclusions: This is the first study to document impaired cortical development after uncomplicated IVH. The impairment was demonstrated by a 16% reduction in cerebral CGM volume at near-term age. The finding supports concerns regarding possible glial precursor cell loss after germinal matrix IVH, but its clinical significance is still unclear. The alteration in brain development demonstrated in this report supports closer neurodevelopmental follow-up monitoring of preterm infants with uncomplicated IVH.