RESUMO
OBJECTIVES: To evaluate whether the number of postnatal infections is associated with abnormal white matter maturation and poorer motor neurodevelopmental outcomes at 36 months of corrected age. STUDY DESIGN: A prospective longitudinal cohort study was undertaken of 219 newborns born preterm at 24-32 weeks of gestational age recruited between 2006 and 2013 with magnetic resonance imaging of the brain both early in life and at term-equivalent age. Postnatal infection was defined as any clinical infection or positive culture ≥72 hours after birth. White matter maturation was assessed by magnetic resonance spectroscopic imaging, magnetic resonance diffusion tensor imaging, and tract-based spatial statistics. Neurodevelopmental outcomes were assessed in 175 (82% of survivors) infants with Bayley Scales of Infant and Toddler Development-III composite scores and Peabody Developmental Motor Scales at 35 months of corrected age (IQR 34-37 months). Infection groups were compared via the Fisher exact test, Kruskal-Wallis test, and generalized estimating equations. RESULTS: Of 219 neonates born preterm (median gestational age 27.9 weeks), 109 (50%) had no postnatal infection, 83 (38%) had 1 or 2 infections, and 27 (12%) had ≥3 infections. Infants with postnatal infections had more cerebellar hemorrhage. Infants with ≥3 infections had lower N-acetylaspartate/choline in the white matter and basal ganglia regions, lower fractional anisotropy in the posterior limb of the internal capsule, and poorer maturation of the corpus callosum, optic radiations, and posterior limb of the internal capsule on tract-based spatial statistics analysis as well as poorer Bayley Scales of Infant and Toddler Development-III (P = .02) and Peabody Developmental Motor Scales, Second Edition, motor scores (P < .01). CONCLUSIONS: In newborns born preterm, ≥3 postnatal infections predict impaired development of the motor pathways and poorer motor outcomes in early childhood.
Assuntos
Infecções Bacterianas/diagnóstico , Encéfalo/diagnóstico por imagem , Deficiências do Desenvolvimento/etiologia , Destreza Motora , Infecções Bacterianas/complicações , Imagem de Tensor de Difusão , Vias Eferentes , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Estudos Longitudinais , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Estudos Prospectivos , Substância BrancaRESUMO
Preterm birth is associated with brain injury and altered cognitive development. However, the consequences of extrauterine development are not clearly distinguished from perinatal brain injury. Therefore, we characterized cortical growth patterns from 30 to 46 postmenstrual weeks (PMW) in 27 preterm neonates (25-32 PMW at birth) without detectable brain injury on magnetic resonance imaging. We introduce surface-based morphometric descriptors that quantify radial (thickness) and tangential (area) change rates. Within a tensor-based morphometry framework, we use a temporally weighted formulation of regression to simultaneously model local age-related changes in cortical gray matter (GM) and underlying white matter (WM) mapped onto the cortical surface. The spatiotemporal pattern of GM and WM development corresponded to the expected gyrification time course of primary sulcal deepening and branching. In primary gyri, surface area and thickness rates were below average along sulcal pits and above average on gyral banks and crests in both GM and WM. Above average surface area rates in GM corresponded to emergence of secondary and tertiary folds. These findings map the development of neonatal cortical morphometry in the context of extrauterine brain development using a novel approach. Future studies may compare this developmental trajectory to preterm populations with brain injury. Hum Brain Mapp 38:4322-4336, 2017. © 2017 Wiley Periodicals, Inc.
Assuntos
Encéfalo/crescimento & desenvolvimento , Substância Cinzenta/crescimento & desenvolvimento , Recém-Nascido Prematuro/crescimento & desenvolvimento , Substância Branca/crescimento & desenvolvimento , Encéfalo/diagnóstico por imagem , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento Tridimensional/métodos , Recém-Nascido , Imageamento por Ressonância Magnética/métodos , Masculino , Tamanho do Órgão , Estudos Prospectivos , Substância Branca/diagnóstico por imagemRESUMO
OBJECTIVE: To identify clinical risk factors for punctate white matter lesions (PWML) on early magnetic resonance imaging (MRI) in 2 cohorts of newborns born extremely preterm in different neonatal centers. STUDY DESIGN: A total of 250 newborns born preterm at less than 28 weeks of gestation (mean 26.4 ± 1.1 weeks) with an early MRI were identified from 2 neonatal centers, in Vancouver, Canada (cohort A, n = 100) and Utrecht, the Netherlands (cohort B, n = 150). Cohort A was imaged as part of a prospective research study and cohort B was imaged as part of routine clinical care. PWML were defined as cluster type foci of hyperintensity on T1-weighted imaging and were identified at a mean postmenstrual age of 31.1 (±1.9) weeks. Multivariable analysis was used to identify clinical factors predictive of PWML. RESULTS: Cluster type PWML were found in 47 newborns born extremely preterm (18.8%) and were more common in cohort A (32%) than in cohort B (10%). Newborns in cohort A generally were sicker than those in cohort B. Multivariable analyses revealed that greater birth weight (B = 0.002; P < .02), grade II-III intraventricular hemorrhage (B = 0.83; P < .02), and cohort A (B = 1.34; P < .0001) were independent predictors of PWML. CONCLUSION: Several risk factors for PWML on early MRI were identified. The interaction among birth weight, intraventricular hemorrhage, and other aspects of postnatal illness as risk factors for PWML warrants further investigation in newborns born extremely preterm and may help to identify modifiable risk factors for PWML.
Assuntos
Doenças do Prematuro/patologia , Imageamento por Ressonância Magnética/métodos , Substância Branca/patologia , Canadá , Feminino , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Países Baixos , Estudos Prospectivos , Fatores de RiscoRESUMO
OBJECTIVE: Very preterm-born neonates (24-32 weeks of gestation) are exposed to stressful and painful procedures during neonatal intensive care. Analgesic and sedation therapies are essential, and opiates and benzodiazepines are commonly used. These medications may negatively impact brain development. The hippocampus may be especially vulnerable to the effects of pain and analgesic and/or sedative therapies and contribute to adverse outcomes. The effect of invasive procedures and analgesic-sedative exposure on hippocampal growth was assessed, as was that of hippocampal growth on neurodevelopmental outcome. METHODS: A total of 138 neonates (51% male, median gestational age = 27.7 weeks) underwent magnetic resonance imaging and diffusion tensor imaging (DTI) scans, early in life (postmenstrual age [PMA] = 32.3 weeks) and at term-equivalent age (PMA = 40.2 weeks). Volumes and DTI measures of axial diffusivity, radial diffusivity, and mean diffusivity (MD) were obtained from the hippocampus. Cognitive, language, and motor abilities were assessed using the Bayley Scales of Infant Development-III at 18.7 months median corrected age. Models testing the association of invasive procedures with hippocampal volumes and DTI measures accounted for birth gestational age, sex, PMA, dose of analgesics/sedatives (fentanyl, morphine, midazolam), mechanical ventilation, hypotension, and surgeries. RESULTS: Total midazolam dose predicted decreased hippocampal volumes (ß = -1.8, p < 0.001) and increased MD (ß = 0.002, p = 0.02), whereas invasive procedures did not (ß = 0, p > 0.5 each). Lower cognitive scores were associated with hippocampal growth (ß = -0.31, p = 0.003), midazolam dose (ß = -0.27, p = 0.03), and surgery (ß = -8.32, p = 0.04). INTERPRETATION: Midazolam exposure was associated with macro- and microstructural alterations in hippocampal development and poorer outcomes consistent with hippocampal dysmaturation. Use of midazolam in preterm neonates, particularly those not undergoing surgery, is cautioned.
Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Deficiências do Desenvolvimento/etiologia , Hipocampo/efeitos dos fármacos , Hipnóticos e Sedativos/efeitos adversos , Midazolam/efeitos adversos , Deficiências do Desenvolvimento/induzido quimicamente , Deficiências do Desenvolvimento/fisiopatologia , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Idade Gestacional , Hipocampo/crescimento & desenvolvimento , Hipocampo/patologia , Humanos , Hipnóticos e Sedativos/administração & dosagem , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido Prematuro , Imageamento por Ressonância Magnética , Masculino , Midazolam/administração & dosagem , Avaliação de Resultados em Cuidados de SaúdeRESUMO
AIM: To characterize corpus callosum development in neonates born very preterm from early in life to term-equivalent age and its relationship with neurodevelopmental outcome at 18 months corrected age. METHOD: In a prospective cohort of 193 neonates born preterm, 24 to 32 weeks' gestation, we used magnetic resonance imaging and diffusion tensor imaging acquired early in life (n=193) and at term-equivalent age (n=159) to measure corpus callosum development: mid-sagittal area (including corpus callosum subdivisions) and length, and fractional anisotropy from the genu and splenium. We examined the association of (1) intraventricular haemorrhage (IVH) and white matter injury (WMI) severity, and (2) neurodevelopmental outcome at 18 months corrected age with corpus callosum development. RESULTS: Severe WMI and severe IVH were strongly associated with reduced corpus callosum area (both p<0.001) and WMI with lower fractional anisotropy (p=0.002). Mild WMI predicted smaller corpus callosum area only posteriorly; mild IVH predicted smaller area throughout. Adverse motor outcome was associated with smaller corpus callosum size in the posterior subdivision (p=0.003). Abnormal cognitive outcomes were associated with lower corpus callosum fractional anisotropy (p=0.008). INTERPRETATION: In newborn infants born very preterm, brain injury is associated with changes in simple metrics of corpus callosum development. In this population, the development of the corpus callosum, as reflected by size and microstructure, is associated with neurodevelopmental outcomes at 18 months corrected age.
Assuntos
Lesões Encefálicas/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Corpo Caloso , Deficiências do Desenvolvimento/diagnóstico por imagem , Imagem de Tensor de Difusão , Lactente Extremamente Prematuro , Estudos de Coortes , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/crescimento & desenvolvimento , Corpo Caloso/patologia , Feminino , Idade Gestacional , Humanos , Processamento de Imagem Assistida por Computador , Lactente , Lactente Extremamente Prematuro/fisiologia , Hemorragias Intracranianas/diagnóstico por imagem , Masculino , Atividade Motora/fisiologiaRESUMO
Accurate automated tissue segmentation of premature neonatal magnetic resonance images is a crucial task for quantification of brain injury and its impact on early postnatal growth and later cognitive development. In such studies it is common for scans to be acquired shortly after birth or later during the hospital stay and therefore occur at arbitrary gestational ages during a period of rapid developmental change. It is important to be able to segment any of these scans with comparable accuracy. Previous work on brain tissue segmentation in premature neonates has focused on segmentation at specific ages. Here we look at solving the more general problem using adaptations of age specific atlas based methods and evaluate this using a unique manually traced database of high resolution images spanning 20 gestational weeks of development. We examine the complimentary strengths of age specific atlas-based Expectation-Maximization approaches and patch-based methods for this problem and explore the development of two new hybrid techniques, patch-based augmentation of Expectation-Maximization with weighted fusion and a spatial variability constrained patch search. The former approach seeks to combine the advantages of both atlas- and patch-based methods by learning from the performance of the two techniques across the brain anatomy at different developmental ages, while the latter technique aims to use anatomical variability maps learnt from atlas training data to locally constrain the patch-based search range. The proposed approaches were evaluated using leave-one-out cross-validation. Compared with the conventional age specific atlas-based segmentation and direct patch based segmentation, both new approaches demonstrate improved accuracy in the automated labeling of cortical gray matter, white matter, ventricles and sulcal cortical-spinal fluid regions, while maintaining comparable results in deep gray matter.
Assuntos
Encéfalo/anatomia & histologia , Processamento de Imagem Assistida por Computador/métodos , Recém-Nascido Prematuro , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Algoritmos , Feminino , Humanos , Recém-Nascido , MasculinoRESUMO
We introduce the STEAM DTI analysis engine: a whole brain voxel-based analysis technique for the examination of diffusion tensor images (DTIs). Our STEAM analysis technique consists of two parts. First, we introduce a collection of statistical templates that represent the distribution of DTIs for a normative population. These templates include various diffusion measures from the full tensor, to fractional anisotropy, to 12 other tensor features. Second, we propose a voxel-based analysis (VBA) pipeline that is reliable enough to identify areas in individual DTI scans that differ significantly from the normative group represented in the STEAM statistical templates. We identify and justify choices in the VBA pipeline relating to multiple comparison correction, image smoothing, and dealing with non-normally distributed data. Finally, we provide a proof of concept for the utility of STEAM on a cohort of 134 very preterm infants. We generated templates from scans of 55 very preterm infants whose T1 MRI scans show no abnormalities and who have normal neurodevelopmental outcome. The remaining 79 infants were then compared to the templates using our VBA technique. We show: (a) that our statistical templates display the white matter development expected over the modeled time period, and (b) that our VBA results detect abnormalities in the diffusion measurements that relate significantly with both the presence of white matter lesions and with neurodevelopmental outcomes at 18months. Most notably, we show that STEAM produces personalized results while also being able to highlight abnormalities across the whole brain and at the scale of individual voxels. While we show the value of STEAM on DTI scans from a preterm infant cohort, STEAM can be equally applied to other cohorts as well. To facilitate this whole-brain personalized DTI analysis, we made STEAM publicly available at http://www.sfu.ca/bgb2/steam.
Assuntos
Mapeamento Encefálico/métodos , Encéfalo/anormalidades , Recém-Nascido Prematuro , Triagem Neonatal/métodos , Substância Branca/anormalidades , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Recém-Nascido , MasculinoRESUMO
OBJECTIVE: To examine the relationship between morphine exposure and growth of the cerebellum and cerebrum in very preterm neonates from early in life to term-equivalent age, as well as to examine morphine exposure and brain volumes in relation to neurodevelopmental outcomes at 18 months corrected age (CA). STUDY DESIGN: A prospective cohort of 136 very preterm neonates (24-32 weeks gestational age) was serially scanned with magnetic resonance imaging near birth and at term-equivalent age for volumetric measurements of the cerebellum and cerebrum. Motor outcomes were assessed with the Peabody Developmental Motor Scales, Second Edition and cognitive outcomes with the Bayley Scales of Infant and Toddler Development, Third Edition at 18 months CA. Generalized least squares models and linear regression models were used to assess relationships between morphine exposure, brain volumes, and neurodevelopmental outcomes. RESULTS: A 10-fold increase in morphine exposure was associated with a 5.5% decrease in cerebellar volume, after adjustment for multiple clinical confounders and total brain volume (P = .04). When infants exposed to glucocorticoids were excluded, the association of morphine was more pronounced, with an 8.1% decrease in cerebellar volume. Morphine exposure was not associated with cerebral volume (P = .30). Greater morphine exposure also predicted poorer motor (P < .001) and cognitive outcomes (P = .006) at 18 months CA, an association mediated, in part, by slower brain growth. CONCLUSIONS: Morphine exposure in very preterm neonates is independently associated with impaired cerebellar growth in the neonatal period and poorer neurodevelopmental outcomes in early childhood. Alternatives to better manage pain in preterm neonates that optimize brain development and functional outcomes are urgently needed.
Assuntos
Analgésicos Opioides/efeitos adversos , Cerebelo/anormalidades , Cerebelo/efeitos dos fármacos , Cérebro/crescimento & desenvolvimento , Deficiências do Desenvolvimento/induzido quimicamente , Morfina/efeitos adversos , Malformações do Sistema Nervoso/induzido quimicamente , Cerebelo/crescimento & desenvolvimento , Cérebro/efeitos dos fármacos , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Imageamento por Ressonância Magnética , Masculino , Estudos ProspectivosRESUMO
AIM: To determine the association between lowest plasma magnesium concentration and brain metabolism, and whether magnetic resonance imaging brain injury patterns moderated the association in hypoxic-ischemic encephalopathy. METHODS: In 131 early (day-of-life 3) and 65 late (day-of-life 10) scans of term encephalopathic infants born between 2004 and 2012, we examined the association of lowest plasma magnesium (until day-of-life 3) on basal ganglia and white matter peak metabolite ratios on magnetic resonance spectroscopy independent of covariates, stratified by the predominant patterns of injury (normal, basal nuclei/total, watershed, multifocal) using multiple linear regression. RESULTS: Lowest plasma magnesium was associated with lower white matter N-acetyl-aspartate/choline in the multifocal pattern on early scan (regression-coefficient, ß: 0.13; 95% CI: 0.04, 0.22) and in the basal nuclei/total pattern on late scan (ß: 0.08; 95% CI: 0.02, 0.15), and was negatively associated with basal ganglia lactate/N-acetyl-aspartate (ß: -0.16; 95% CI: -0.05, -0.28) and lactate/choline (ß: -0.1; 95% CI: -0.03, -0.17) ratio in the basal nuclei/total pattern on late scan independent of hypomagnesaemia correction, cooling and postmenstrual age at scan. Lowest plasma magnesium was not associated with metabolite ratios in other brain injury patterns. CONCLUSION: In infants with hypoxic-ischaemic encephalopathy, predominant patterns of brain injury moderated the association between lowest plasma magnesium in the first three days of life and impaired brain metabolism.
Assuntos
Encéfalo/metabolismo , Hipóxia-Isquemia Encefálica/metabolismo , Magnésio/sangue , Feminino , Humanos , Recém-Nascido , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: To examine whether specific neonatal factors differentially influence cerebellar subregional volumes and to investigate relationships between subregional volumes and outcomes in very preterm children at 7 years of age. STUDY DESIGN: Fifty-six children born very preterm (24-32 weeks gestational age) followed longitudinally from birth underwent 3-dimensional T(1)-weighted neuroimaging at median age 7.6 years. Children with severe brain injury were excluded. Cerebellar subregions were automatically segmented using the multiple automatically generated templates algorithm. The relation between cerebellum subregional volumes (adjusted for total brain volume and sex) and neonatal clinical factors were examined using constrained principal component analysis. Cognitive and visual-motor integration functions in relation to cerebellar volumes were also investigated. RESULTS: Higher neonatal procedural pain and infection, as well as other clinical factors, were differentially associated with reduced cerebellar volumes in specific subregions. After adjusting for clinical risk factors, neonatal procedural pain was distinctively associated with smaller volumes bilaterally in the posterior VIIIA and VIIIB lobules. Specific smaller cerebellar subregional volumes were related to poorer cognition and motor/visual integration. CONCLUSIONS: In very preterm children, exposure to painful procedures, as well as additional neonatal risk factors such as infection, were associated with reduced cerebellar volumes in specific subregions and poorer outcomes at school age.
Assuntos
Cerebelo/patologia , Recém-Nascido Prematuro , Infecções/fisiopatologia , Dor/fisiopatologia , Criança , Desenvolvimento Infantil , Cognição , Feminino , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Fatores de RiscoRESUMO
Preterm infants develop differently than those born at term and are at higher risk of brain pathology. Thus, an understanding of their development is of particular importance. Diffusion tensor imaging (DTI) of preterm infants offers a window into brain development at a very early age, an age at which that development is not yet fully understood. Recent works have used DTI to analyze structural connectome of the brain scans using network analysis. These studies have shown that, even from infancy, the brain exhibits small-world properties. Here we examine a cohort of 47 normal preterm neonates (i.e., without brain injury and with normal neurodevelopment at 18 months of age) scanned between 27 and 45 weeks post-menstrual age to further the understanding of how the structural connectome develops. We use full-brain tractography to find white matter tracts between the 90 cortical and sub-cortical regions defined in the University of North Carolina Chapel Hill neonatal atlas. We then analyze the resulting connectomes and explore the differences between weighting edges by tract count versus fractional anisotropy. We observe that the brain networks in preterm infants, much like infants born at term, show high efficiency and clustering measures across a range of network scales. Further, the development of many individual region-pair connections, particularly in the frontal and occipital lobes, is significantly correlated with age. Finally, we observe that the preterm infant connectome remains highly efficient yet becomes more clustered across this age range, leading to a significant increase in its small-world structure.
Assuntos
Encéfalo/anatomia & histologia , Imagem de Tensor de Difusão/métodos , Rede Nervosa/anatomia & histologia , Encéfalo/crescimento & desenvolvimento , Conectoma , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Rede Nervosa/crescimento & desenvolvimentoRESUMO
OBJECTIVE: To determine whether prenatal diagnosis lowers the risk of preoperative brain injury by assessing differences in the incidence of preoperative brain injury across centers. STUDY DESIGN: From 2 prospective cohorts of newborns with complex congenital heart disease studied by preoperative cerebral magnetic resonance imaging, one cohort from the University Medical Center Utrecht (UMCU) and a combined cohort from the University of California San Francisco (UCSF) and University of British Columbia (UBC), patients with aortic arch obstruction were selected and their imaging and clinical course reviewed. RESULTS: Birth characteristics were comparable between UMCU (n = 33) and UCSF/UBC (n = 54). Patients had a hypoplastic aortic arch with either coarctation/interruption or hypoplastic left heart syndrome. In subjects with prenatal diagnosis, there was a significant difference in the prevalence of white matter injury (WMI) between centers (11 of 22 [50%] at UMCU vs 4 of 30 [13%] at UCSF/UBC; P < .01). Prenatal diagnosis was protective for WMI at UCSF/UBC (13% prenatal diagnoses vs 50% postnatal diagnoses; P < .01), but not at UMCU (50% vs 46%, respectively; P > .99). Differences in clinical practice between prenatally diagnosed subjects at UMCU vs UCSF/UBC included older age at surgery, less time spent in the intensive care unit, greater use of diuretics, less use of total parenteral nutrition (P < .01), and a greater incidence of infections (P = .01). In patients diagnosed postnatally, the prevalence of WMI was similar in the 2 centers (46% at UMCU vs 50% at UCSF/UBC; P > .99). Stroke prevalence was similar in the 2 centers regardless of prenatal diagnosis (prenatal diagnosis: 4.5% at Utrecht vs 6.7% at UCSF/UBC, P = .75; postnatal diagnosis: 9.1% vs 13%, respectively, P > .99). CONCLUSION: Prenatal diagnosis can be protective for WMI, but this protection may be dependent on specific clinical management practices that differ across centers.
Assuntos
Síndromes do Arco Aórtico/cirurgia , Cardiopatias Congênitas/cirurgia , Leucoencefalopatias/prevenção & controle , Humanos , Recém-Nascido , Leucoencefalopatias/diagnóstico , Leucoencefalopatias/patologia , Nutrição Parenteral Total , Diagnóstico Pré-Natal , Cuidados Pré-Operatórios , Fatores de RiscoRESUMO
Cranial fasciitis is a fibroblastic lesion found in the cranium of children three weeks to six years of age. It most commonly manifests as a solitary, rapid growing mass on the scalp with frequent involvement of underlying bone and occasional intracranial expansion. Patients with cranial fasciitis may present with a wide range of associated symptoms. Otologic symptoms such as otalgia, otorrhea, hearing loss and middle ear effusion are not frequently encountered. We present a case of cranial fasciitis with intracranial involvement and associated otologic symptoms in a four year old boy with subsequent follow up 14 years later.
Assuntos
Fasciite/patologia , Fasciite/cirurgia , Osso Temporal/patologia , Osso Temporal/cirurgia , Biópsia , Pré-Escolar , Diagnóstico Diferencial , Fasciite/diagnóstico por imagem , Humanos , Masculino , Osso Temporal/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Preterm infants are exposed to multiple painful procedures in the neonatal intensive care unit (NICU) during a period of rapid brain development. Our aim was to examine relationships between procedural pain in the NICU and early brain development in very preterm infants. METHODS: Infants born very preterm (N=86; 24-32 weeks gestational age) were followed prospectively from birth, and studied with magnetic resonance imaging, 3-dimensional magnetic resonance spectroscopic imaging, and diffusion tensor imaging: scan 1 early in life (median, 32.1 weeks) and scan 2 at term-equivalent age (median, 40 weeks). We calculated N-acetylaspartate to choline ratios (NAA/choline), lactate to choline ratios, average diffusivity, and white matter fractional anisotropy (FA) from up to 7 white and 4 subcortical gray matter regions of interest. Procedural pain was quantified as the number of skin-breaking events from birth to term or scan 2. Data were analyzed using generalized estimating equation modeling adjusting for clinical confounders such as illness severity, morphine exposure, brain injury, and surgery. RESULTS: After comprehensively adjusting for multiple clinical factors, greater neonatal procedural pain was associated with reduced white matter FA (ß=-0.0002, p=0.028) and reduced subcortical gray matter NAA/choline (ß=-0.0006, p=0.004). Reduced FA was predicted by early pain (before scan 1), whereas lower NAA/choline was predicted by pain exposure throughout the neonatal course, suggesting a primary and early effect on subcortical structures with secondary white matter changes. INTERPRETATION: Early procedural pain in very preterm infants may contribute to impaired brain development.
Assuntos
Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/patologia , Recém-Nascido Prematuro/crescimento & desenvolvimento , Unidades de Terapia Intensiva Neonatal , Fibras Nervosas Mielinizadas/patologia , Dor/patologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Encéfalo/patologia , Córtex Cerebral/metabolismo , Imagem de Tensor de Difusão/métodos , Feminino , Seguimentos , Humanos , Recém-Nascido , Recém-Nascido Prematuro/metabolismo , Masculino , Fibras Nervosas Mielinizadas/metabolismo , Dor/metabolismo , Medição da Dor/métodos , Estudos ProspectivosRESUMO
BACKGROUND: Brain injury in term neonatal hypoxic-ischemic encephalopathy (HIE) emerges on magnetic resonance imaging (MRI) by day 3. This study aimed to address the relationship of MRI, diffusion tensor imaging (DTI), and MR spectroscopic imaging (MRSI) findings on days 1 and 3 in a prospective cohort of term newborns with HIE. METHODS: A total of 24 term newborns with HIE were prospectively studied with MRI on days 1 and 3; 19 were imaged with DTI and MRSI on days 1 and 3. MRI was assessed using validated scores. The relationship between MRI, DTI, and MRSI values on days 1 and 3 was determined using linear regression for repeated measures. RESULTS: Conventional MRI showed a complex variation of findings from day 1 to 3. In gray matter, mean diffusivity (Dav) and metabolite ratios measured on day 1 were predictive of values on day 3 (all P ≤ 0.04). In white matter, Dav, fractional anisotropy (FA), and N-acetylaspartate (NAA)/choline on days 1 and 3 were strongly related (all P ≤ 0.003). Hypothermia appeared to attenuate the severity and progression of brain injury in the six treated newborns. CONCLUSION: In term newborns with HIE, quantitative MR values on days 1 and 3 are strongly associated, providing an objective measure of injury before qualitative images.
Assuntos
Hipóxia-Isquemia Encefálica/patologia , Imageamento por Ressonância Magnética/métodos , Feminino , Humanos , Recém-Nascido , MasculinoRESUMO
BACKGROUND: Term newborns with congenital heart disease (CHD) show delayed brain development as early as the third trimester, especially in single-ventricle physiology (SVP). Mechanisms causing delayed brain development in CHD are uncertain but may include impaired fetal brain blood flow. Our objective was to determine if cardiac anatomy associated with obstruction to antegrade flow in the ascending aorta is predictive of delayed brain development as measured by diffusion tensor imaging and magnetic resonance spectroscopic (MRS) imaging. METHODS: Echocardiograms from 36 term newborns with SVP were reviewed for the presence of aortic atresia and the diameter of the ascending aorta. Quantitative magnetic resonance imaging parameters measuring brain microstructural (fractional anisotropy (FA) and average diffusivity (Dav)) or metabolic development (N-acetylaspartate (NAA) and lactate/choline (Lac/Cho)) were recorded. RESULTS: Increasing NAA/Cho and white matter (WM) FA, and decreasing Dav and Lac/Cho characterize normal brain development. Consistent with the hypothesis that delayed brain development is related to impaired brain perfusion, smaller ascending aortic diameter and aortic atresia were associated with higher Dav and lower WM FA. Echocardiogram variables were not associated with brain metabolic measures. CONCLUSIONS: These observations support the hypothesis that obstruction to fetal cerebral blood flow impairs brain microstructural development.
Assuntos
Encéfalo/ultraestrutura , Ventrículos Cerebrais/anatomia & histologia , Encéfalo/crescimento & desenvolvimento , Ecocardiografia , Feminino , Humanos , Recém-Nascido , MasculinoRESUMO
INTRODUCTION: Intensive resuscitation at birth has been linked to intraventricular haemorrhage (IVH) in the preterm neonate. However, the impact of less intensive resuscitation on more subtle alterations in brain metabolic development is largely unknown. Our objective was to determine the relationship between the intensity of neonatal resuscitation following preterm birth on brain metabolic development. METHODS: One hundred thirty-three very preterm-born neonates (median gestational age [GA] 27 ± 2 weeks) underwent MR spectroscopic imaging early in life (median postmenstrual age 32 weeks) and again at term-equivalent age (median 40 weeks). Severity of white matter injury, IVH and cerebellar haemorrhage on magnetic resonance imaging were scored. Ratios of N-acetylaspartate (NAA) and lactate to choline (Cho) were calculated in eight regions of interest and were assessed in relation to intensiveness of resuscitation strategy (bag and mask, continuous positive airway pressure [CPAP], intubation, cardiopulmonary resuscitation [CPR]). RESULTS: Within the first hour of life, 14 newborns had no intervention, 3 received bag and mask, 30 had CPAP, 79 were intubated and 7 had CPR. Resuscitated infants were more likely to have IVH (p = 0.02). More intensive resuscitation was associated with decreased NAA/Cho maturation (p < 0.001, adjusting for birth GA). Metabolic development was similar in neonates requiring CPAP in comparison to those receiving no intervention. The change in lactate/Cho did not differ across resuscitation categories (p = 0.8). CONCLUSIONS: Intensity of resuscitation at birth is related to changes in metabolic brain development from early in life to term-equivalent age. Results suggest that preventing the need for intensive neonatal resuscitation may provide an opportunity to improve brain development in preterm neonates.
Assuntos
Encefalopatias Metabólicas/epidemiologia , Encefalopatias Metabólicas/reabilitação , Lesões Encefálicas/epidemiologia , Lesões Encefálicas/reabilitação , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/reabilitação , Ressuscitação/estatística & dados numéricos , Colúmbia Britânica/epidemiologia , Causalidade , Comorbidade , Feminino , Humanos , Recém-Nascido Prematuro , Masculino , Fatores de Risco , Resultado do TratamentoRESUMO
INTRODUCTION: Infection is a risk factor for adverse neurodevelopmental outcome in preterm newborns. Our objective was to characterize the association of postnatal infection with adverse microstructural and metabolic brain development in premature newborns. RESULTS: In 34/117 newborns studied, clinical signs were accompanied by positive cultures whereas 17 had clinical signs of sepsis alone. White matter injury (WMI) was identified in 34 newborns. In multivariate regression models, infected newborns had brain imaging measures indicative of delayed brain development: lower N-acetylaspartate/choline, elevated average diffusivity (D(AV)), and decreased white matter fractional anisotropy. These widespread brain abnormalities were found in both newborns with positive-culture infection and in those with clinical infection. DISCUSSION: These findings suggest that postnatal infection, even without a positive culture, is an important risk factor for widespread abnormalities in brain development. These abnormalities extend beyond brain injuries apparent with conventional magnetic resonance injury (MRI). METHODS: 117 preterm newborns (24-32 wk gestation) were studied prospectively at a median of 32.0 and 40.3 wk ostmenstrual age with MRI (WMI, hemorrhage), magnetic resonance (MR) spectroscopy (metabolism), and diffusion tensor imaging (microstructure). Newborns were categorized as having "no infection," "clinical infection," or "positive-culture infection." We compared brain injuries as well as metabolic and microstructural development across these infection groups.
Assuntos
Infecções Bacterianas/complicações , Encéfalo/anormalidades , Encéfalo/crescimento & desenvolvimento , Recém-Nascido Prematuro , Encéfalo/patologia , Estudos de Coortes , Imagem de Tensor de Difusão , Feminino , Humanos , Técnicas In Vitro , Recém-Nascido , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Análise Multivariada , Estudos Prospectivos , Estudos Retrospectivos , Fatores de RiscoRESUMO
Children born very preterm, even when intelligence is broadly normal, often experience selective difficulties in executive function and visual-spatial processing. Development of structural cortical connectivity is known to be altered in this group, and functional magnetic resonance imaging (fMRI) evidence indicates that very preterm children recruit different patterns of functional connectivity between cortical regions during cognition. Synchronization of neural oscillations across brain areas has been proposed as a mechanism for dynamically assigning functional coupling to support perceptual and cognitive processing, but little is known about what role oscillatory synchronization may play in the altered neurocognitive development of very preterm children. To investigate this, we recorded magnetoencephalographic (MEG) activity while 7-8 year old children born very preterm and age-matched full-term controls performed a visual short-term memory task. Very preterm children exhibited reduced long-range synchronization in the alpha-band during visual short-term memory retention, indicating that cortical alpha rhythms may play a critical role in altered patterns functional connectivity expressed by this population during cognitive and perceptual processing. Long-range alpha-band synchronization was also correlated with task performance and visual-perceptual ability within the very preterm group, indicating that altered alpha oscillatory mechanisms mediating transient functional integration between cortical regions may be relevant to selective problems in neurocognitive development in this vulnerable population at school age.
Assuntos
Ritmo alfa/fisiologia , Sincronização Cortical , Memória de Curto Prazo/fisiologia , Algoritmos , Criança , Cognição/fisiologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Magnetoencefalografia , Masculino , Estimulação Luminosa , Desempenho Psicomotor/fisiologia , Percepção Espacial/fisiologia , Percepção Visual/fisiologia , Escalas de WechslerRESUMO
OBJECTIVE: To hypothesize that detailed examination of early cerebellar volumes in time would distinguish differences in cerebellar growth associated with intraventricular hemorrhage (IVH) and white matter injury in preterm infants. STUDY DESIGN: Preterm newborns at the University of California San Francisco (n = 57) and the University of British Columbia (n = 115) were studied with serial magnetic resonance imaging scans near birth and again at near term-equivalent age. Interactive semi-automated tools were used to determine volumes of the cerebellar hemispheres. RESULTS: Adjusting for supratentorial brain injury, cerebellar hemorrhage, and study site, cerebellar volume increased 1.7 cm(3)/week postmenstrual age (95% CI, 1.6-1.7; P < .001). More severe supratentorial IVH was associated with slower growth of cerebellar volumes (P < .001). Volumes by 40 weeks were 1.4 cm(3) lower in premature infants with grade 1 to 2 IVH and 5.4 cm(3) lower in infants with grade 3 to 4 IVH. The same magnitude of decrease was found between ipsilateral and contralateral IVH. No association was found with severity of white matter injury (P = .3). CONCLUSIONS: Early effects of decreased cerebellar volume associated with supratentorial IVH in either hemisphere may be a result of concurrent cerebellar injury or direct effects of subarachnoid blood on cerebellar development.