Perinatal factors and regional brain volume abnormalities at term in a cohort of extremely low birth weight infants.

Nehal A Parikh,Robert E Lasky,Jon E Tyson,Georgia Mcdavid,Kathleen A Kennedy,Jean-Claude Baron

doi:10.1371/journal.pone.0062804

Abstract

Our objective was to investigate diverse clinical antecedents of total and regional brain volume abnormalities and white matter hyperintensity volume on term MRI in extremely low birth weight (birth weight ≤1000 g) survivors. A consecutive cohort of extremely low birth weight infants who survived to 38 weeks postmenstrual age (n = 122) and a control group of 16 healthy term newborns underwent brain MRI at term-equivalent age. Brain volumes were measured using semi-automated and manual segmentation methods. Using multivariable linear regression, clinical antecedents were correlated with volumes of total brain tissue, white matter hyperintensities, and regional tissues/structures, adjusted for age at MRI, total cranial volume, and total tissue volume. Regional brain volumes were markedly reduced in extremely low birth weight infants as compared to term newborns (relative difference range: −11.0%, −35.9%). Significant adverse clinical associations for total brain tissue volume included: small for gestational age, seizures, caffeine therapy/apnea of prematurity, duration of parenteral nutrition, pulmonary hemorrhage, and white matter injury (p<0.01 for each; relative difference range: −1.4% to −15.0%). Surgery for retinopathy of prematurity and surgery for necrotizing enterocolitis or spontaneous intestinal perforation were significantly associated with increasing volume of white matter hyperintensities. Regional brain volumes are sensitive to multiple perinatal factors and neonatal morbidities or interventions. Brain growth measurements in extremely low birth weight infants can advance our understanding of perinatal brain injury and development.

Highlights

While survival rates for extremely low birth weight infants (ELBW; #1000 g) over the past two decades have improved dramatically, rates of neurodevelopmental impairments (NDI) remain alarmingly high [1], [2]
As we have described previously, this software systematically mislabeled regions of periventricular and subcortical white matter hyperintensities (WMH) as cerebrospinal fluid (CSF), when WM intensity approached CSF intensity values
We observed globally smaller cerebral tissue and structural volumes in a cohort of high-risk ELBW infants as compared to term controls. These marked reductions were accompanied by a compensatory increase in CSF volume and smaller total brain size, suggesting cerebral atrophy was partially responsible for smaller volumes

Summary

Introduction

While survival rates for extremely low birth weight infants (ELBW; #1000 g) over the past two decades have improved dramatically, rates of neurodevelopmental impairments (NDI) remain alarmingly high [1], [2]. Regional brain volume abnormalities and white matter signal abnormalities on T2weighted MRI scans, known as diffuse excessive high signal intensity (DEHSI), are the most common findings in ELBW infants on MRI at term-equivalent age [5,6,7,8]. In preliminary investigations, such abnormalities have been associated with cerebral palsy, memory deficits, and intellectual impairments [6], [9,10,11,12,13]. Development of more objective quantitative measures of DEHSI and regional volumes may reduce measurement error and resolve this debate [16]

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