RESUMO
OBJECTIVES: To investigate how glucose abnormalities correlate with brain function on amplitude-integrated electroencephalography (aEEG) in infants with neonatal encephalopathy. STUDY DESIGN: Neonates born at full term with encephalopathy were enrolled within 6 hours of birth in a prospective cohort study at a pediatric academic referral hospital. Continuous interstitial glucose monitors and aEEG were placed soon after birth and continued for 3 days. Episodes of hypoglycemia (≤50 mg/dL; ≤2.8 mmol/L) and hyperglycemia (>144 mg/dL; >8.0 mmol/L) were identified. aEEG was classified in 6-hour epochs for 3 domains (background, sleep-wake cycling, electrographic seizures). Generalized estimating equations assessed the relationship of hypo- or hyperglycemia with aEEG findings, adjusting for clinical markers of hypoxia-ischemia (Apgar scores, umbilical artery pH, and base deficit). RESULTS: Forty-five infants (gestational age 39.5 ± 1.4 weeks) were included (24 males). During aEEG monitoring, 16 episodes of hypoglycemia were detected (9 infants, median duration 77.5, maximum 220 minutes) and 18 episodes of hyperglycemia (13 infants, median duration 237.5, maximum 3125 minutes). Epochs of hypoglycemia were not associated with aEEG changes. Compared with epochs of normoglycemia, epochs of hyperglycemia were associated with worse aEEG background scores (B 1.120, 95% CI 0.501-1.738, P < .001), less sleep-wake cycling (B 0.587, 95% CI 0.417-0.757, P < .001) and more electrographic seizures (B 0.433, 95% CI 0.185-0.681, P = .001), after adjusting for hypoxia-ischemia severity. CONCLUSIONS: In neonates with encephalopathy, epochs of hyperglycemia were temporally associated with worse global brain function and seizures, even after we adjusted for hypoxia-ischemia severity. Whether hyperglycemia causes neuronal injury or is simply a marker of severe brain injury requires further study.
Assuntos
Encefalopatias/diagnóstico por imagem , Eletroencefalografia/métodos , Hiperglicemia/complicações , Hipoglicemia/complicações , Convulsões/diagnóstico por imagem , Centros Médicos Acadêmicos , Índice de Apgar , Glicemia/análise , Encefalopatias/epidemiologia , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Hiperglicemia/diagnóstico , Hipoglicemia/diagnóstico , Hipóxia Encefálica/diagnóstico por imagem , Hipóxia Encefálica/fisiopatologia , Recém-Nascido , Masculino , Prevalência , Estudos Prospectivos , Convulsões/epidemiologia , Índice de Gravidade de DoençaRESUMO
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
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
OBJECTIVE: To investigate the contribution of hypoglycemia in the first 24 hours after birth to brain injury in term newborns at risk for neonatal encephalopathy. STUDY DESIGN: A prospective cohort of 94 term neonates born between 1994 and 2010 with early postnatal brain magnetic resonance imaging studies were analyzed for regions of brain injury. Neurodevelopmental outcome was assessed at 1 year of age. RESULTS: Hypoglycemia (glucose <46 mg/dL) in the first 24 hours after birth was detected in 16% of the cohort. Adjusting for potential confounders of early perinatal distress and need for resuscitation, neonatal hypoglycemia was associated with a 3.72-fold increased odds of corticospinal tract injury (P=.047). Hypoglycemia was also associated with 4.82-fold increased odds of 1-point worsened neuromotor score (P=.038) and a 15-point lower cognitive and language score on the Bayley Scales of Infant Development (P=.015). CONCLUSION: Neonatal hypoglycemia is associated with additional risks in the setting of neonatal encephalopathy with increased corticospinal tract injury and adverse motor and cognitive outcomes.
Assuntos
Encefalopatias/etiologia , Desenvolvimento Infantil , Hipoglicemia/complicações , Sistema Nervoso/crescimento & desenvolvimento , Encefalopatias/epidemiologia , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Prospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To investigate the relationship between cerebellar hemorrhage in preterm infants seen on magnetic resonance imaging (MRI), but not on ultrasonography, and neurodevelopmental outcome. STUDY DESIGN: Images from a cohort study of MRI in preterm newborns were reviewed for cerebellar hemorrhage. The children were assessed at a mean age of 4.8 years with neurologic examination and developmental testing using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. RESULTS: Cerebellar hemorrhage was detected on both ultrasonography and MRI in 3 of the 131 preterm newborns evaluated, whereas smaller hemorrhages were seen only on MRI in 10 newborns (total incidence, 10%). Adjusting for gestational age at birth, intraventricular hemorrhage, and white matter injury, cerebellar hemorrhage detectable solely by MRI was associated with a 5-fold increased odds of abnormal neurologic examination compared with newborns without cerebellar hemorrhage (outcome data in 74%). No association with the Wechsler Preschool and Primary Scale of Intelligence, Third Edition score was found. CONCLUSIONS: Cerebellar hemorrhage is not uncommon in preterm newborns. Although associated with neurologic abnormalities, hemorrhage seen only on MRI is associated with much more optimistic outcomes than that visible on ultrasonography.
Assuntos
Cerebelo/patologia , Hemorragia Cerebral/patologia , Deficiências do Desenvolvimento/etiologia , Recém-Nascido Prematuro , Imageamento por Ressonância Magnética/métodos , Estudos de Casos e Controles , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Pré-Escolar , Estudos de Coortes , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/fisiopatologia , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Testes de Inteligência , Modelos Lineares , Modelos Logísticos , Masculino , Exame Neurológico/métodos , Medição de Risco , Índice de Gravidade de Doença , Ultrassonografia DopplerRESUMO
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.