Recent resting-state functional MRI investigations have demonstrated that much of the large-scale functional network architecture supporting motor, sensory and cognitive functions in older pediatric and adult populations is present in term- and prematurely-born infants. Application of new analytical approaches can help translate the improved understanding of early functional connectivity provided through these studies into predictive models of neurodevelopmental outcome. One approach to achieving this goal is multivariate pattern analysis, a machine-learning, pattern classification approach well-suited for high-dimensional neuroimaging data. It has previously been adapted to predict brain maturity in children and adolescents using structural and resting state-functional MRI data. In this study, we evaluated resting state-functional MRI data from 50 preterm-born infants (born at 23–29 weeks of gestation and without moderate–severe brain injury) scanned at term equivalent postmenstrual age compared with data from 50 term-born control infants studied within the first week of life. Using 214 regions of interest, binary support vector machines distinguished term from preterm infants with 84% accuracy (p < 0.0001). Inter- and intra-hemispheric connections throughout the brain were important for group categorization, indicating that widespread changes in the brain's functional network architecture associated with preterm birth are detectable by term equivalent age. Support vector regression enabled quantitative estimation of birth gestational age in single subjects using only term equivalent resting state-functional MRI data, indicating that the present approach is sensitive to the degree of disruption of brain development associated with preterm birth (using gestational age as a surrogate for the extent of disruption). This suggests that support vector regression may provide a means for predicting neurodevelopmental outcome in individual infants.

Background Preterm infants are at risk for white matter injury and adverse neurodevelopmental outcomes. Methods Serial diffusion tensor MRI data were obtained from very preterm infants (N=78) born <30 weeks gestation imaged up to four times from 26-42 weeks postmenstrual age. Slopes were calculated for fractional anisotropy (FA) and mean diffusivity (MD) within regions of interest for infants with ≥2 scans (N=50). Sixty-five children underwent neurodevelopmental testing at age two years. Results FA slope for the posterior limb of the internal capsule was greater than other regions. The anterior limb of the internal capsule (ALIC), corpus callosum and optic radiations demonstrated greater FA slope with increasing gestational age. Infants with PDA had lower FA slope in the ALIC. MD slope was lower with prolonged ventilation or lack of antenatal steroids. At age 2 years, lower motor scores were associated with lower FA in the left but higher FA in the right inferior temporal lobe at term-equivalent. Better social-emotional competence was related to lower FA in the left cingulum bundle. Conclusion This study demonstrates regional variability in the susceptibility/sensitivity of white matter maturation to perinatal factors and relationships between altered diffusion measures and developmental outcomes in preterm neonates.

Objective: To assess the extent to which social and family factors explain variability in cognitive, language, and motor development among very preterm (VPT; <30 weeks of gestation) children from 2 to 5 years of age. Study design: As part of a longitudinal study, VPT children recruited as neonates were assessed at 2 (n=87) and 5 (n=83) years using standardized tests of cognitive, language, and motor ability alongside demographically-matched full term (FT) children (n=63). For VPT children, developmental change scores were calculated for each domain to assess within-individual variability to 5 years of age. Multivariate regression and mixed-effect models examined social risk index, parenting stress, family functioning, and maternal intellectual ability as predictors of developmental variation among VPT children. Results: VPT children demonstrated poorer cognitive, language, and motor abilities than FT children at 2 (P ≤ .001) and 5 (p<.002) years of age. Social adversity was associated with cognitive (p<.001) and language (p<.001) outcomes at both ages, with parenting stress also related to cognitive outcomes (p=.03). Infant medical risk was associated with motor outcome at 5 years (p=.01). VPT children showed considerable within-individual variation between assessments. Among VPT children, neonatal white matter abnormalities predicted worsening cognitive (p=.04) and motor development (p=.01). Social risk index predicted worsening language development (p=.04), but this association was subsequently explained by dysfunctional maternal affective involvement (p=.01) and lower maternal intellectual ability (p=.05). Conclusions: Both clinical and socioenvironmental factors are associated with cognitive, language and motor developmental variation among VPT children from infancy to early school age.

Spatial and functional gradients of development have been described for the maturation of cerebral gray and white matter using histological and radiological approaches. We evaluated these patterns in very preterm (VPT) infants using diffusion tensor imaging. Data were obtained from 3 groups: 1) 22 VPT infants without white matter injury (WMI), of whom all had serial MRI studies during the neonatal period, 2) 19 VPT infants with WMI, of whom 3 had serial MRI studies and 3) 12 healthy, term-born infants. Regions of interest were placed in the cortical gray and adjacent white matter in primary motor, primary visual, visual association, and prefrontal regions. From the MRI data at term-equivalent postmenstrual age, differences in mean diffusivity were found in all areas between VPT infants with WMI and the other 2 groups. In contrast, minimal differences in fractional anisotropy were found between the 3 groups. These findings suggest that cortical maturation is delayed in VPT infants with WMI when compared with term control infants and VPT infants without WMI. From the serial MRI data from VPT infants, synchronous development between gray and white matter was evident in all areas and all groups, with maturation in primary motor and sensory regions preceding that of association areas. This finding highlights the regionally varying but locally synchronous nature of the development of cortical gray matter and its adjacent white matter.

Background Very preterm (VPT; <30 weeks gestation) children are a heterogeneous group, yet the co‐occurrence of psychiatric and neurodevelopmental impairments remains unclear. Moreover, the clinical and socio‐environmental factors that promote resilient developmental outcomes among VPT children are poorly understood. Methods One hundred and twenty five children (85 VPT and 40 full‐term) underwent neurodevelopmental evaluation at age 5‐years. Parents and teachers completed measures of internalizing, externalizing, attention‐deficit/hyperactivity (ADHD), and autism symptoms. Psychiatric and neurodevelopmental measures were analyzed using Latent Profile Analysis. Multinomial regression examined the extent that infant, sociodemographic, and family factors, collected prospectively from birth to follow‐up, independently differentiated resilient and impaired children. Results Four latent profiles were identified, including a Typically Developing Group which represented 27.1% of the VPT group and 65.0% of the full‐term group, an At‐Risk Group with mild psychiatric and neurodevelopmental problems (VPT 44.7%, full‐term 22.5%), a Psychiatric Group with moderate‐to‐severe psychiatric ratings (VPT 12.9%, full‐term 10.0%), and a school‐based Inattentive/Hyperactive Group (VPT 15.3%, full‐term 2.5%). Clinical diagnoses were highest among the Psychiatric Group (80%). Factors that differentiated resilient and impaired subgroups of VPT children included prolonged exposure to maternal psychosocial distress (p ≤ .04), current family dysfunction (p ≤ .05), and maternal ADHD symptoms (p ≤ .02), whereas social risk index scores differentiated resilient and impaired full‐term children (p < .03). Conclusions Lower levels of maternal distress, family dysfunction, and maternal ADHD symptoms were associated with resilience among VPT children. Maternal distress and family dysfunction are modifiable factors to be targeted as part of psychiatric interventions embedded in the long‐term care of VPT children.