IVH, germinal matrix haemorrhageintraventricular haemorrhage; HPI, haemorrhagic periventricular infarction; PCW, postconceptional week; WM, white matter; WMI, white matter injury. Sciences Library. Protected by copyright. on May 17, 2021 at CU Anschutz Strauss Health http://fn.bmj.com/ Arch Dis Child Fetal Neonatal Ed: first published as 10.1136/archdischild-2020-319450 on 10 May 2021. Downloaded from Soni R, et al. Arch Dis Child Fetal Neonatal Ed 2021;0:F1–F8. doi:10.1136/archdischild-2020-319450 F3 Review The neural architecture of each sensory system is built at 22–40 weeks’ gestation and further develops in the neonatal period. The hearing system is fully developed at 20 PCW. At 23 PCW, an unborn baby can respond to loud noises. A newborn baby’s eyes are susceptible to bright light but are short-sighted at only 8–12 inches in front of their face. Adverse neonatal experiences can alter brain development and subsequent behaviour in preterm infants.15 16 They are exposed to many stimuli from which they would have been protected in utero, including the NICU environment and its related stressful events. Calming experiences are few, including lower levels of maternal oxytocin. The nature of delivery of sensory experience received in the NICU can overstimulate later developing sensory systems (auditory and visual) and understimulate earlier developing systems (tactile and vestibular), while also reducing the amount and availability of intersensory redundancy.14 The interplay of these sensory experiences and its influence on future neurodevelopment is not yet well understood. BRAIN MRI ABNORMALITIES ASSOCIATED WITH PREMATURITY Survival at lower gestations has seen the emergence of new phenotypes of preterm brain injury. With the incidence of germinal matrix haemorrhage-intraventricular haemorrhage (GMH-IVH) and cystic periventricular leucomalacia (PVL) reducing,17 a more diffuse pattern of white matter (WM) injury, characterised by loss of oligodendrocyte precursors, is more frequently seen. Punctate WM lesions are the most common MRI abnormality in preterms imaged at term-equivalent age and are associated with an increased risk of poor motor outcome18 (figure 3). The term ‘encephalopathy of prematurity’ describes the combination of destructive and dysmaturational effects leading to abnormal WM and grey matter (GM) development.19 Neonatal MRI has shown a signature pattern of preterm birth that includes alterations in WM and GM microstructure, impaired cortical folding and disturbances in regional brain growth. These structural changes reflect a dysconnectivity of neural networks and atypical development of cortical and deep GM structures.8 20 While MRI has advanced our understanding of preterm brain injury, predicting neurodevelopmental outcome based on lesions other than PVL and haemorrhagic periventricular infarction is still elusive.21 Brain growth Although brain growth is rapid between 25 and 40 weeks in a preterm baby on the NICU, the growth trajectory is less than in a healthy fetus over the same duration. MRI studies of preterm infants have identified reduced cortical (figure 4) and subcortical GM volumes22 diminished cerebellar volumes23 and alterations in thalamocortical development at term-equivalent age.24 The long-term effects of prematurity are observed by alterations in WM and GM volumes seen in adolescence.25 Microstructural brain development of WM and GM Diffusion MRI (dMRI) has demonstrated altered WM development in preterm infants without focal lesions,26 which is related to neurodevelopmental performance in early childhood27 and adolescence. Using dMRI to assess macrostructural connectivity,28 the organisation of structural brain networks during the preterm period has been characterised, demonstrating a relative preservation of specific core connections at term-equivalent age.29 Of great interest, Batalle and colleagues recently demonstrated relative preservation of these specific core connections; whereas regional connectivity involving thalamus, cerebellum, superior frontal lobe, cingulate gyrus and short-range corticocortical connections were related to the degree of prematurity.30 Compared with term-born infants, preterm infants at termcorrected age have impaired cortical development with decreased cortical folding24; reduced GM volumes are associated with fetal growth restriction and slower postnatal growth.31 Factors associated with the preterm birth signature have been elegantly reviewed by Boardman and Counsell. Maternal factors associated with altered brain development include chorioamnionitis, fetal growth restriction, socioeconomic deprivation, and prenatal alcohol, drug and stress exposures; fetal factors include nutrition, pain and medication, and variation conferred by the genome/epigenome.20 NEURODEVELOPMENTAL OUTCOMES OF PRETERM INFANTS Although rates of severe neurological disability, cerebral palsy (CP) and intellectual disability are reduced compared with previously reported, 5%–15% of very preterm survivors are still affected. Milder cognitive disabilities, learning difficulties and behavioural problems are detected in 25%–50% of preterm survivors at preschool and school age.9 32 While the extremely preterm