Early general movements and brain magnetic resonance imaging at term-equivalent age in infants born < 30 weeks' gestation
Introduction
The high prevalence of neurodevelopmental impairment in infants born very preterm (< 32 weeks' gestation) is a challenging issue for clinicians working in neonatal care. Neurodevelopmental assessment in the neonatal period in conjunction with neuroimaging affords valuable information for counselling parents and targeting infants for early intervention [1]. There is increasing recognition that preterm birth may disrupt the growth and maturational process of neural development and organisation [2]. As development occurs at variable rates within different cerebral regions and structures according to gestational age, preterm birth can result in diverse cerebral alterations depending on the region of insult, and the timing of disruption to maturational processes, particularly myelination [3]. Abnormal brain development can occur secondary to injury, or as a result of disruption of neuromaturational processes following preterm birth [4].
Cerebral magnetic resonance imaging (MRI) conducted at term-equivalent age (TEA) is a sensitive tool that can provide important information about preterm infant brain injury and structure, which is associated with long-term neurodevelopment, including motor and cognitive outcomes [5], [6]. However, it is crucial to note, that MRI alone cannot predict the functional outcome for individual infants with 100% accuracy [7], [8]. Neurodevelopmental assessments have an important role as they can identify infants at risk for later neurological impairment, and may enhance the prognostic utility of MRI if used in combination [9], [10], [11]. Prechtl's qualitative assessment of General Movements (GMA) [12] is an observational assessment of the infant's spontaneous movements with good predictive validity for neurodevelopmental outcomes, including cerebral palsy, motor impairment and cognitive outcomes [7], [13], [14]. Previous reports indicate that cerebral MRI and the GMA are reliable as complementary assessments to predict later neurodevelopmental outcome in very preterm infants [9], [10], [11]. Abnormal general movements (GMs) at one and three months' corrected age are associated with white matter abnormalities on MRI at TEA [15], [16]; and combined GMA and white matter abnormality predict motor outcomes at 12 months' corrected age, with abnormal GMs and moderate-severe white matter abnormality demonstrating 100% sensitivity for predicting cerebral palsy in our previous study of very preterm infants [9].
While there is evidence of associations between brain structure [17] and injury on MRI at TEA and GMs assessed post-term [15], [16], [18], [19], the relationships between GMs assessed prior to term and cerebral MRI remains largely unexplored, particularly in the early preterm phase. This is important information for two reasons. Firstly, to understand the relationships between cerebral structure, particularly size and maturation, and early neurodevelopment in very preterm infants, for whom critical brain development occurs in the neonatal intensive care environment. Secondly, to help clinicians identify optimal times for GMA so that infants with adverse neurodevelopment can be targeted for early intervention, including within the neonatal intensive care environment [20], [21], [22], and to ensure timely referrals and access to community-based early intervention services upon discharge from hospital. Only two studies have included GMs assessed prior to term and cerebral MRI [11], [23] and neither study examined the relationship of GMs assessed prior to term, or at TEA, and MRI. The largest study [11] reported on the predictive accuracy for neurodevelopmental outcome of concurrent GMs and MRI assessed close to term at 36 weeks' postmenstrual age (PMA); MRI scoring included three measures of brain injury, but not brain size or maturation. MRI scoring systems that only measure brain injury may not be sensitive given that the prevalence of brain injury is low [6].
The aim of this study was to examine the relationships between GMs assessed from birth to TEA and brain MRI at TEA in infants born < 30 weeks' gestation. It was hypothesised that abnormal GMs assessed soon after birth and at subsequent assessments would be associated with MRI-defined cerebral abnormalities at TEA.
Section snippets
Participants
Infants born < 30 weeks' gestation were recruited from the Royal Women's Hospital, Melbourne, Australia, between January 2011 and December 2013 as part of a larger prospective longitudinal cohort study [24]. Infants with congenital abnormalities known to affect neurodevelopment, non-English speaking parents (as there was no funding for interpreters), and those unlikely to survive in the early neonatal period as assessed by clinical staff, were excluded from the study. Infants were enrolled within
Participants
One hundred and forty nine infants born < 30 weeks' gestation were recruited from the Royal Women's Hospital in Melbourne between January 2011 and Dec. 2013 (Fig. 1). Six infants died prior to term age. Of the remaining 143 infants, there were 32 infants who did not have a MRI, with the reasons outlined in Fig. 1. As the MRI scan was an optional component of the larger study, there were 14 infants who did not have a MRI due to parent preference and one scan was not usable due to movement
Discussion
This study demonstrated that abnormal GMs in very preterm infants in both the preterm and term periods were associated with more brain abnormality and smaller brains on MRI at TEA. Our study provides further validation of the GMA as a measure of neurological function and that GMs quality reflects central nervous system integrity in very preterm infants. Unlike other studies that have assessed GMs prior to TEA [11], [23], the MRI analysis in the current study included measures of brain size and
Conclusion
Abnormal GMs in very preterm infants were associated with more marked brain abnormality and smaller brains on MRI at TEA. Abnormal GMs assessed prior to term were associated with larger interhemispheric distance and higher cortical grey matter abnormality on MRI at TEA, indicating that abnormal GMs are an early marker for disrupted brain development in very preterm infants. Term-equivalent was highlighted as an important age for GMA given the associations of abnormal GMs with smaller brain size
Acknowledgements
This study was funded by grants from the National Health and Medical Research Council (Centre of Research Excellence in Newborn Medicine 1060733; Project Grants 1024516 and 1028822, Career Development Fellowship 1108714-AJS, 1085754-DKT and 1053609-KJL; Early Career Fellowship 1053787-JLYC, Senior Research Fellowship 1081288-PJA); Australian Postgraduate Association Scholarship, University of Melbourne (JEO), Murdoch Childrens Research Institute and the Victorian Government's Operational
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