White Matter Injury and General Movements in High-Risk Preterm Infants

Peyton, Colleen; Yang, Edward; Msall, Michael E.; Adde, Lars; Støen, Ragnhild; Fjørtoft, Toril; Bos, Arie; Einspieler, Christa; Zhou, Yi; Schreiber, Michael D.; Marks, Jeremy D.; Drobyshevsky, Alexander

doi:10.3174/ajnr.a4955

Cited by 37 publications

(45 citation statements)

References 29 publications

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“…repetitive self-grooming and a reduction in social play behavior. In line with these findings, recent clinical studies revealed an association between diffuse WMI and motor abnormalities in preterm infants (Guo et al, 2017;Peyton et al, 2016Peyton et al, , 2017. Also, multiple studies have demonstrated that preterm infants are at risk to develop ASD later in life (Dudova et al, 2014;Johnson et al, 2010;Joseph et al, 2017;Kuzniewicz et al, 2014;Limperopoulos et al, 2008;Pritchard et al, 2016;Treyvaud et al, 2013).…”

Section: Discussionmentioning

confidence: 84%

“…Additionally, activation of microglia and astrogliosis are important pathophysiological hallmarks of diffuse WMI (Buser et al, ; Haynes et al, ; Verney et al, ). Functionally, WMI is associated with behavioral, cognitive, motor and psychological problems, like autism spectrum disorders (ASD), later in life (Back & Miller, ; Dudova et al, ; Guo et al, ; Johnson, Hollis, Kochhar, Hennessy, Wolke, & Marlow, ; Joseph et al, ; Kuzniewicz et al, ; Limperopoulos et al, ; Peyton et al, ; Pritchard et al, ; Treyvaud et al, ). While antenatal administration of magnesium sulfate in women at risk for preterm delivery reduces the risk of cerebral palsy in the fetus (Crowther, Hiller, Doyle, & Haslam, ; Doyle, Crowther, Middleton, Marret, & Rouse, ; Gano et al, ; Rouse et al, ), limited treatment options are currently available to protect preterm infants against diffuse WMI.…”

Section: Introductionmentioning

confidence: 99%

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Combined fetal inflammation and postnatal hypoxia causes myelin deficits and autism‐like behavior in a rat model of diffuse white matter injury

Tilborg

Achterberg

Kammen

et al. 2017

Glia

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Diffuse white matter injury (WMI) is a serious problem in extremely preterm infants, and is associated with adverse neurodevelopmental outcome, including cognitive impairments and an increased risk of autism‐spectrum disorders. Important risk factors include fetal or perinatal inflammatory insults and fluctuating cerebral oxygenation. However, the exact mechanisms underlying diffuse WMI are not fully understood and no treatment options are currently available. The use of clinically relevant animal models is crucial to advance knowledge on the pathophysiology of diffuse WMI, allowing the definition of novel therapeutic targets. In the present study, we developed a multiple‐hit animal model of diffuse WMI by combining fetal inflammation and postnatal hypoxia in rats. We characterized the effects on white matter development and functional outcome by immunohistochemistry, MRI and behavioral paradigms. Combined fetal inflammation and postnatal hypoxia resulted in delayed cortical myelination, microglia activation and astrogliosis at P18, together with long‐term changes in oligodendrocyte maturation as observed in 10 week old animals. Furthermore, rats with WMI showed impaired motor performance, increased anxiety and signs of autism‐like behavior, i.e. reduced social play behavior and increased repetitive grooming. In conclusion, the combination of fetal inflammation and postnatal hypoxia in rats induces a pattern of brain injury and functional impairments that closely resembles the clinical situation of diffuse WMI. This animal model provides the opportunity to elucidate pathophysiological mechanisms underlying WMI, and can be used to develop novel treatment options for diffuse WMI in preterm infants.

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Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Combined fetal inflammation and postnatal hypoxia causes myelin deficits and autism‐like behavior in a rat model of diffuse white matter injury

Tilborg

Achterberg

Kammen

et al. 2017

Glia

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“…Phenomenologically, assessment of infants' spontaneous behavior has recently gained a lot of interest for three reasons: First, it is well accepted that the highest ecological validity comes from studies performed in subject's native environment, i.e., the lab or hospital environment is at most sub-optimal for genuinely assessing neurodevelopmental performance. Second, the novel recording and analysis methodologies have made it possible to study subject's spontaneous activities in both lab and other environments [19,25] Third, both fundamental and applied research has shown that infant's spontaneous movements may provide an important global window to the infant brain function [7,17]. Besides bodily movements per se, spontaneous movements also support the development of higher cognitive functions through the organization of the action-perception-loop, gradually also enabling intentional exploration of the surrounding world.…”

Section: Introductionmentioning

confidence: 99%

Automatic Posture and Movement Tracking of Infants with Wearable Movement Sensors

Airaksinen

Räsänen

Ilén

et al. 2020

Sci Rep

102

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Infant's spontaneous movements mirror integrity of brain networks, and thus also predict the future development of higher cognitive functions. Early recognition of infants with compromised motor development holds promise for guiding early therapies to improve lifelong neurocognitive outcomes. It has been challenging, however, to assess motor performance in ways that are objective and quantitative. Novel wearable technology has shown promise for offering efficient, scalable and automated methods in movement assessment. Here, we describe the development of an infant wearable, a multi-sensor smart jumpsuit that allows mobile data collection during independent movements. A deep learning algorithm, based on convolutional neural networks (CNNs), was then trained using multiple human annotations that incorporate the substantial inherent ambiguity in movement classifications. We also quantify the substantial ambiguity of a human observer, allowing its transfer to improving the automated classifier. Comparison of different sensor configurations and classifier designs shows that four-limb recording and end-toend CNN classifier architecture allows the best movement classification. Our results show that quantitative tracking of independent movement activities is possible with a human equivalent accuracy, i.e. it meets the human inter-rater agreement levels in infant posture and movement classification.

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“…Infant and Toddler Development -Third Edition (BSID-III) at 2 years of corrected age. 18 Studies focusing on very preterm children and the potential association between DTI metrics at term age and later motor development at school age are scarce. In this study, our aim was to assess whether DTI metrics at term age are associated with motor development at 11 years of age in very preterm children.…”

Section: Dti Metrics and Motor Outcomes Measured With The Bayley Scalmentioning

confidence: 99%

“…In these studies, the DTI metrics of the corpus callosum, posterior limb of the internal capsule and corticospinal tracts have been reported to associate with motor development . However, there is also one study reporting no associations between DTI metrics and motor outcomes measured with the Bayley Scales of Infant and Toddler Development – Third Edition (BSID‐III) at 2 years of corrected age …”

Section: Introductionmentioning

confidence: 99%

Diffusion tensor imaging is associated with motor outcomes of very preterm born children at 11 years of age

et al. 2019

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Aim Very preterm children born <32 weeks of gestation are at risk for motor difficulties such as cerebral palsy and developmental coordination disorder. This study explores the association between diffusion tensor imaging metrics at term and motor outcomes at 11 years of age. Methods A cohort of 37 very preterm infants (mean gestational age 29 4/7, SD 2 0/7) born in 2004‐2006 in Turku University Hospital underwent diffusion tensor imaging at term. A region of interest analysis of fractional anisotropy and mean diffusivity was performed. Motor outcomes at 11 years of age were measured with the Movement Assessment Battery for Children – Second Edition. Results The diffusion metrics of the corpus callosum (genu P = .005, splenium P = .049), the left corona radiata (P = .035) and the right optic radiation (P = .017) were related to later motor performance. Mean diffusivity decreased and fractional anisotropy increased in proportion to the improving performance. Conclusion The diffusion metrics of the genu and splenium of the corpus callosum, the left corona radiata and the right optic radiation at term were associated with motor skills at 11 years of age. Diffusion tensor imaging should be further studied as a potential tool in recognising children at risk for motor impairment.

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White Matter Injury and General Movements in High-Risk Preterm Infants

Cited by 37 publications

References 29 publications

Combined fetal inflammation and postnatal hypoxia causes myelin deficits and autism‐like behavior in a rat model of diffuse white matter injury

Combined fetal inflammation and postnatal hypoxia causes myelin deficits and autism‐like behavior in a rat model of diffuse white matter injury

Automatic Posture and Movement Tracking of Infants with Wearable Movement Sensors

Diffusion tensor imaging is associated with motor outcomes of very preterm born children at 11 years of age

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