Invited Review: Factors associated with atypical brain development in preterm infants: insights from magnetic resonance imaging

Abstract

Preterm birth (PTB) is a leading cause of neurodevelopmental and neurocognitive impairment in childhood and is closely associated with psychiatric disease. The biological and environmental factors that confer risk and resilience for healthy brain development and long-term outcome after PTB are uncertain, which presents challenges for risk stratification and for the discovery and evaluation of neuroprotective strategies. Neonatal magnetic resonance imaging reveals a signature of PTB that includes dysconnectivity of neural networks and atypical development of cortical and deep grey matter structures. Here we provide a brief review of perinatal factors that are associated with the MRI signature of PTB. We consider maternal and foetal factors including chorioamnionitis, foetal growth restriction, socioeconomic deprivation and prenatal alcohol, drug and stress exposures; and neonatal factors including co-morbidities of PTB, nutrition, pain and medication during neonatal intensive care and variation conferred by the genome/epigenome. Association studies offer the first insights into pathways to adversity and resilience after PTB. Future challenges are to analyse quantitative brain MRI data with collateral biological and environmental data in study designs that support causal inference, and ultimately to use the output of such analyses to stratify infants for clinical trials of therapies designed to improve outcome.

Keywords: brain; development; magnetic resonance imaging; neonate; preterm birth.

Figure 1

(A) (i) T1‐ and (ii) T2‐weighted images of an infant at 26 weeks gestational age (GA) and (iii) T1‐ and (iv) T2‐weighted images of an infant at 42 weeks GA at the level of the basal ganglia. (B) Diffusion magnetic resonance imaging maps at the level of the basal ganglia (i) fractional anisotropy, FA (ii) mean diffusivity, MD (iii) orientation dispersion index, ODI and (iv) neurite density index, NDI. (C) Brain segmentation in an infant born at 27⁺⁴ weeks gestational age and imaged at 41⁺² weeks postmenstrual age. Key: Green = cortical grey matter, blue = white matter, grey = deep grey matter, pink = extracerebral cerebrospinal fluid. (D) Correlation between gestational age at birth and FA measures in white matter assessed using tract‐based spatial statistics. Mean FA skeleton (green) overlaid on mean FA map in the axial plane. Voxels showing a significant correlation (P < 0.05) between GA at birth FA are shown in red. (E) Diffusion MR tractography (i) arcuate fasciculus and (ii) optic radiations

Figure 2

Maternal, foetal and neonatal factors associated with brain development in preterm infants