Background and Purpose WM injury is the dominant form of injury in preterm infants. However, other cerebral structures, including deep GM and cerebellum, can also be affected by injury and/or impaired growth. Current MRI injury assessment scales are subjective and challenging to apply. Thus, we developed a new assessment tool and applied it to MRI studies obtained from VPT infants at term-equivalent postmenstrual age to describe the spectrum of brain abnormalities. Methods MRI scans from 97 VPT infants (<30 weeks gestation) and 22 healthy term-born infants were evaluated retrospectively. The severity of brain injury (defined by signal abnormalities) and impaired brain growth (defined with biometrics) was scored in the WM, cortical GM, deep GM and cerebellum. Perinatal variables for clinical risks were collected from medical records. Results Of 97 VPT infants, brain injury was observed in WM (n=23), deep GM (n=5) and cerebellum (n=23). Combining measures of injury and impaired growth showed moderate-severe abnormalities most commonly in WM (n=38) and cerebellum (n=32), but still notable in cortical GM (n=16) and deep GM (n=11). None of 22 term-born infants had moderate-severe abnormalities. Multiple clinical risk factors, including prolonged intubation, prolonged parenteral nutrition, postnatal corticosteroid use and postnatal sepsis, were associated with increased global MRI abnormality. Conclusions VPT infants demonstrate a high prevalence of injury and growth impairment in both WM and GM. This MRI scoring system provides a more comprehensive and objective classification of the nature and extent of abnormalities in VPT infants than existing measures.

Brain Injury and Altered Brain Growth in Preterm Infants: Predictors and PrognosisWHAT'S KNOWN ON THIS SUBJECT: Term MRI can assist in identifying the nature and extent of brain injury in preterm infants. However, brain injury detected by MRI does not fully account for neurodevelopmental impairments, particularly cognitive and behavioral impairments, common in preterm survivors. WHAT THIS STUDY ADDS:In addition to brain injury, an assessment of brain growth by using one-dimensional measurements on MRI is helpful for predicting neurodevelopment. Two different patterns of impaired brain growth are observed that relate independently to early cognitive development in preterm infants. abstract BACKGROUND: To define the nature and frequency of brain injury and brain growth impairment in very preterm (VPT) infants by using MRI at term-equivalent age and to relate these findings to perinatal risk factors and 2-year neurodevelopmental outcomes.METHODS: MRI scans at term-equivalent age from 3 VPT cohorts (n = 325) were reviewed. The severity of brain injury, including periventricular leukomalacia and intraventricular and cerebellar hemorrhage, was graded. Brain growth was assessed by using measures of biparietal width (BPW) and interhemispheric distance. Neurodevelopmental outcome at age 2 years was assessed across all cohorts (n = 297) by using the Bayley Scales of Infant Development, Second Edition (BSID-II) or Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), and evaluation for cerebral palsy. RESULTS:Of 325 infants, 107 (33%) had some grade of brain injury and 33 (10%) had severe injury. Severe brain injury was more common in infants with lower Apgar scores, necrotizing enterocolitis, inotropic support, and patent ductus arteriosus. Severe brain injury was associated with delayed cognitive and motor development and cerebral palsy. Decreased BPW was related to lower gestational age, inotropic support, patent ductus arteriosus, necrotizing enterocolitis, prolonged parenteral nutrition, and oxygen at 36 weeks and was associated with delayed cognitive development. In contrast, increased interhemispheric distance was related to male gender, dexamethasone use, and severe brain injury. It was also associated with reduced cognitive development, independent of BPW.CONCLUSIONS: At term-equivalent age, VPT infants showed both brain injury and impaired brain growth on MRI. Severe brain injury and impaired brain growth patterns were independently associated with perinatal risk factors and delayed cognitive development. Pediatrics 2014;134:e444-e453 Dr Kidokoro contributed to the study concept and design, assessed the MRI findings, performed the statistical analyses, and wrote the first draft of the manuscript; Drs Anderson and Doyle contributed to the collection of the Australian data presented in this article and revised the manuscript for important intellectual content; Dr Woodward contributed to the collection of the New Zealand data presented in this article and revised the manuscript for important i...

Objective To evaluate associations between neonatal intensive care unit (NICU) room type (open ward and private room) and medical outcomes; neurobehavior, electrophysiology and brain structure at hospital discharge; and developmental outcomes at two years of age. Study design In this prospective longitudinal cohort study, we enrolled 136 preterm infants born <30 weeks gestation from an urban, 75-bed level III NICU from 2007-2010. Upon admission, each participant was assigned to a bedspace in an open ward or private room within the same hospital, based on space and staffing availability, where they remained for the duration of hospitalization. The primary outcome was developmental performance at two years of age (n=86 infants returned for testing, which was 83% of survivors) measured using the Bayley Scales of Infant and Toddler Development, 3rd Edition. Secondary outcomes were 1) medical factors throughout the hospitalization, 2) neurobehavior, and 3) cerebral injury and maturation (determined by magnetic resonance imaging and electroencephalography). Results At term equivalent age, infants in private rooms were characterized by a diminution of normal hemispheric asymmetry and a trend toward having lower amplitude integrated electroencephalography cerebral maturation scores [p= 0.02; β=−0.52 (CI −0.95, −0.10)]. At age two years, infants from private rooms had lower language scores [p= 0.006; β=−8.3 (CI −14.2, −2.4)] and a trend toward lower motor scores [p= 0.02; β=−6.3 (CI −11.7, −0.99)], which persisted after adjustment for potential confounders. Conclusion These findings raise concerns that highlight the need for further research into the potential adverse effects of different amounts of sensory exposure in the NICU environment.

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Background Uncertainty remains about the rate of specific psychiatric disorders and associated predictive factors for very preterm (VPT) children. The aims of this study were to document rates of psychiatric disorders in VPT children aged 7 years compared with term born children, and to examine potential predictive factors for psychiatric diagnoses in VPT children. Methods Participants were 177 VPT and 65 term born children. Perinatal medical data were collected, which included brain abnormalities detected using magnetic resonance imaging. The Infant-Toddler Social-Emotional Assessment (ITSEA) and Strengths and Difficulties Questionnaire (SDQ) were administered at 2 and 5 years respectively. At 7 years of age, the Developmental and Well-being Assessment (DAWBA) was used to indicate psychiatric diagnoses. Results Compared with term born children, VPT children had three times the odds of meeting criteria for any psychiatric diagnosis at age 7 years (odds ratio 3.03; 95% confidence interval 1.23, 7.47, p = .02). The most common diagnoses were anxiety disorders (11% VPT, 8% term), attention-deficit/hyperactivity disorder (10% VPT, 3% term) and autism spectrum disorder (4.5% VPT, 0% term). For VPT children, those with severe global brain abnormalities (p = .02), those who displayed social-emotional problems at age 5 (p = .000) and those with higher social risk at age 7 (p = .001) were more likely to meet criteria for a psychiatric illness at age 7. Conclusions Compared with term born children, VPT children have higher rates of psychiatric diagnoses at early school age, predicted by neonatal brain abnormalities, prior social-emotional problems and social factors.

ObjectiveWe investigated whether particular demographic, maternal psychosocial, and infant factors identified mothers of very preterm infants at risk for postpartum depression or anxiety at the time of discharge from a level III urban Neonatal Intensive Care Unit (NICU).Study DesignA racially diverse cohort of mothers (N=73) of preterm infants (gestational age <30 weeks) completed a comprehensive questionnaire at discharge from the NICU assessing postpartum depression, anxiety, and psychosocial and demographic factors. Additionally, infants underwent brain magnetic resonance imaging prior to discharge.ResultTwenty percent of mothers had clinically significant levels of depression while 43% had moderate-severe anxiety. Being married (p<.01), parental role alteration (p<.01) and prolonged ventilation (p<.05) were associated with increased depressive symptoms. No psychosocial, demographic, or infant factors, including severity of brain injury, were associated with state anxiety levels.ConclusionMaternal factors, such as marital status, stress from parental role alteration, and infant factors, such as prolonged ventilation, are associated with increased depression. However, clinically significant levels of anxiety are common in mothers of very preterm infants with few identifiable risk factors. These findings support the need for universal screening within the NICU.

Objective Preterm children are at risk for social-emotional difficulties, including autism and attention deficit hyperactivity disorder. We assessed the relationship of regional brain development in preterm children, evaluated via MRI at term-equivalent postmenstrual age (TEA), to later social-emotional difficulties. Method MR images obtained at TEA from 184 very preterm infants (gestation <30 weeks or birthweight <1250 g) were analyzed for white matter abnormalities, hippocampal volume, and brain metrics. 111 infants underwent diffusion tensor imaging, which provided values for fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Social-emotional development was assessed with the Infant Toddler Social and Emotional Assessment (ITSEA) at age 2 and the Strengths and Difficulties Questionnaire (SDQ) at age 5. Results Higher ADC in the right orbitofrontal cortex was associated with social-emotional problems at age 5 (peer problems, p<0.01). In females, smaller hippocampal volume was associated with increased hyperactivity (p<0.01), peer problems (p<0.05) and SDQ total score (p<0.01). In males, a smaller frontal region was associated with poorer prosocial (p<0.05) scores. Many of the hippocampal findings remained significant after adjusting for birthweight z score, intelligence, social risk, immaturity at birth, and parental mental health. These associations were present in children who had social-emotional problems in similar domains at age 2 and those who did not. Conclusions Early alterations in regional cerebral development in very preterm infants relate to specific deficits in social-emotional performance by school-age. These results vary by gender. Our results provide further evidence for a neuroanatomical basis for behavioral challenges found in very preterm children.

Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term born controls. Neonatal brain abnormalities, and in particular deep grey matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children, especially global, white-matter, grey-matter and cerebellar abnormalities. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function.