Neonatal physiological correlates of near-term brain development on MRI and DTI in very-low-birth-weight preterm infants

Abstract

Structural brain abnormalities identified at near-term age have been recognized as potential predictors of neurodevelopment in children born preterm. The aim of this study was to examine the relationship between neonatal physiological risk factors and early brain structure in very-low-birth-weight (VLBW) preterm infants using structural MRI and diffusion tensor imaging (DTI) at near-term age.Structural brain MRI, diffusion-weighted scans, and neonatal physiological risk factors were analyzed in a cross-sectional sample of 102 VLBW preterm infants (BW ≤ 1500 g, gestational age (GA) ≤ 32 weeks), who were admitted to the Lucile Packard Children's Hospital, Stanford NICU and recruited to participate prior to routine near-term brain MRI conducted at 36.6 ± 1.8 weeks postmenstrual age (PMA) from 2010 to 2011; 66/102 also underwent a diffusion-weighted scan. Brain abnormalities were assessed qualitatively on structural MRI, and white matter (WM) microstructure was analyzed quantitatively on DTI in six subcortical regions defined by DiffeoMap neonatal brain atlas. Specific regions of interest included the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, the thalamus, and the globus pallidus. Regional fractional anisotropy (FA) and mean diffusivity (MD) were calculated using DTI data and examined in relation to neonatal physiological risk factors including gestational age (GA), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and sepsis, as well as serum levels of C-reactive protein (CRP), glucose, albumin, and total bilirubin.Brain abnormalities were observed on structural MRI in 38/102 infants including 35% of females and 40% of males. Infants with brain abnormalities observed on MRI had higher incidence of BPD (42% vs. 25%) and sepsis (21% vs. 6%) and higher mean and peak serum CRP levels, respectively, (0.64 vs. 0.34 mg/dL, p = .008; 1.57 vs. 0.67 mg/dL, p= .006) compared to those without. The number of signal abnormalities observed on structural MRI correlated to mean and peak CRP (rho = .316, p = .002; rho = .318, p= .002). The number of signal abnormalities observed on MRI correlated with thalamus MD (left: r= .382, p= .002; right: r= .400, p= .001), controlling for PMA-at-scan. Thalamus WM microstructure demonstrated the strongest associations with neonatal risk factors. Higher thalamus MD on the left and right, respectively, was associated with lower GA (r = −.322, p = .009; r= −.381, p= .002), lower mean albumin (r = −.276, p= .029; r= −.385, p= .002), and lower mean bilirubin (r = −.293, p= .020; r= −.337 p= .007).Results suggest that at near-term age, thalamus WM microstructure may be particularly vulnerable to certain neonatal risk factors. Interactions between albumin, bilirubin, phototherapy, and brain development warrant further investigation. Identification of physiological risk factors associated with selective vulnerability of certain brain regions at near-term age may clarify the etiology of neurodevelopm...

A New Ultrasound Marker for Bedside Monitoring of Preterm Brain Growth

“…Several studies showed impaired thalamus volume and extreme vulnerability of the thalamus to be neonatal risk factors after preterm birth. 23,24 Whether thalamic injury or growth impairment directly influences CCF length needs to be further studied.…”

Neonatal brain microstructure correlates of neurodevelopment and gait in preterm children 18–22 mo of age: an MRI and DTI study

“…(BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and sepsis (19)(20)(21). This study examined nearterm brain structure in VLBW preterm neonates in relation to neurodevelopment and gait at 18-22 mo of adjusted age.…”

“…Serum CRP was sampled 3.72 ± 1.9 times over the first 2 postnatal wk, obtained through a search conducted with Stanford Center for Clinical Informatics and STRIDE. Analysis of neonatal clinical risk factors and neuroimaging in the same cohort was previously published (21).…”

Preterm neuroimaging and neurodevelopmental outcome: a focus on intraventricular hemorrhage, post-hemorrhagic hydrocephalus, and associated brain injury

“…This is suggestive of more advanced development in posterior and central areas at term [98, 99]. There is also a male-female DTI difference in preterms; males have a higher CC splenium FA and genu MD [100]. Preterm children with ventriculomegaly (as well as moderate to severe white matter injury) tend to have a slower increase of FA values and higher MDs than preterm comparisons [101].…”

“…Ventricular dilation causes compression of the posterior limb of the internal capsule (PLIC), resulting in a decrease in the extra-cellular space and increase in fiber crowding, coherence, and alignment among the PLIC [100, 102]. Multiple studies show that in term children with hydro­cephalus, PLIC FA values are significantly lower than comparisons [103, 104, 106].…”