OBJECTIVES: The goal was to examine whether indomethacin use, gender, neonatal, and sociodemographic factors predict patterns of receptive language development from 3 to 12 years of age in preterm children. METHODS: A total of 355 children born in 1989-1992 with birth weights of 600 to 1250 g were evaluated at 3, 4.5, 6, 8, and 12 years with the Peabody Picture Vocabulary Test-Revised. Hierarchical growth modeling was used to explore differences in language trajectories. RESULTS: From 3 to 12 years, preterm children displayed catch-up gains on the Peabody Picture Vocabulary Test-Revised. Preterm children started with an average standardized score of 84.1 at 3 years and gained 1.2 points per year across the age period studied. Growth-curve analyses of Peabody Picture Vocabulary Test-Revised raw scores revealed an indomethacin-gender effect on initial scores at 3 years, with preterm boys assigned randomly to receive indomethacin scoring, on average, 4.2 points higher than placebo-treated boys. However, the velocity of receptive vocabulary development from 3 to 12 years did not differ for the treatment groups. Children with severe brain injury demonstrated slower gains in skills over time, compared with those who did not suffer severe brain injury. Significant differences in language trajectories were predicted by maternal education and minority status. CONCLUSION: Although indomethacin yielded an initial benefit for preterm boys, this intervention did not alter the developmental trajectory of receptive language scores. Severe brain injury leads to long-term sequelae in language development, whereas a socioeconomically advantaged environment supports better language development among preterm children.

Converging data suggest recovery from injury in the preterm brain. We used functional Magnetic Resonance Imaging (fMRI) to test the hypothesis that cerebral connectivity involving Wernicke's area and other important cortical language regions would differ between preterm (PT) and term (T) control school age children during performance of an auditory language task. Fifty-four PT children (600 - 1250 g birth weight) and 24 T controls were evaluated using an fMRI passive language task and neurodevelopmental assessments including: the Wechsler Intelligence Scale for Children - III (WISC - III), the Peabody Individual Achievement Test - Revised (PIAT-R) and the Peabody Picture Vocabulary Test - Revised (PPVT- R) at 8 years of age. Neural activity was assessed for language processing and the data were evaluated for connectivity and correlations to cognitive outcomes. We found PT subjects scored significantly lower on all components of the WISC - III (p < 0.009), the PIAT- R reading comprehension test (p = 0.013), and the PPVT-R (p = 0.001) compared to term subjects. Connectivity analyses revealed significantly stronger neural circuits in PT children between Wernicke's area and the right inferior frontal gyrus (R IFG, Broca's area homologue) and both the left and the right supramarginal gyri (SMG) components of the inferior parietal lobules (p < 0.02 for all). We conclude that PT subjects employ neural systems for auditory language function at school age differently than T controls; these alterations may represent a delay in maturation of neural networks or the engagement of alternate circuits for language processing.

OBJECTIVES: This study examined risk of maltreatment among children exiting foster care using a statewide sample of children reunified between 2001 and 2004 in Rhode Island. The objectives were:(1) to compare rates of maltreatment following parental reunification for youth in care as a result of maltreatment with those in care for other reasons; and (2) to assess the effects of child, family, and case characteristics on rates of re-maltreatment among children placed in foster care due to maltreatment. METHOD: A longitudinal dataset of all reunified cases was matched with state records of substantiated Child Protective Service (CPS) investigations. Two Cox proportional hazards models were tested. The first model compared rates of subsequent maltreatment for two groups: children in foster care as a result of maltreatment, and those in care for other reasons. The second model investigated the effects of child, family, and case characteristics on re-maltreatment rates for those in care as a result of maltreatment. RESULTS: Children in foster care due to maltreatment were significantly more likely to be maltreated following reunification. Among children in foster care due to maltreatment, factors that raised risk for re-maltreatment included a previous foster care placement, exiting care from a non-relative foster home, and removal due to neglect. Older adolescents had lower rates of re-maltreatment than infants. Child neglect was the primary type of recurrent maltreatment that occurred following reunification. CONCLUSIONS: Supports are needed for families about to be reunified, particularly when the removal was prompted by incidents of abuse or neglect. Incidents of neglect are particularly likely and appropriate services should specifically target factors contributing to neglect. Cases involving youth with a history of repeated foster care placement or in which non-relative placements are utilized may need additional supports. PRACTICE IMPLICATIONS: This study suggests that services should be developed to minimize the risk for recurrent maltreatment following reunification. Services would be most useful for high-risk cases prior to reunification and during the first year following reunification. Understanding the risks associated with maltreatment will help guide development of appropriate interventions.

OBJECTIVES. Our goals were to compare cognitive, language, behavioral, and educational outcomes of preterm children to term controls and to evaluate the impact of neonatal brain injury, indomethacin, and environmental risk factors on intellectual function at 12 years of age. METHODS. A total of 375 children born in 1989-1992 with birth weights of 600 to 1250 g enrolled in the Indomethacin Intraventricular Hemorrhage Prevention Trial and 111 controls were evaluated. Neuropsychometric testing, neurologic examination, and interviews on educational needs were completed. Severe brain injury was defined as the presence of grade 3 to 4 indomethacin intraventricular hemorrhage, periventricular leukomalacia, or severe ventriculomegaly on cranial ultrasound. RESULTS. On the Wechsler Scales of Intelligence for Children, the preterm cohort obtained a full-scale IQ of 87.9 +/- 18.3, verbal IQ of 90.8 +/- 18.9, and performance IQ of 86.8 +/- 17.9. Preterm children obtained scores 6 to 14 points lower than term controls on all psychometric tests after adjustment for sociodemographic factors. On the Clinical Evaluation of Language Fundamentals (test of basic language skills), 22% to 24% of preterm children scored in the abnormal ranges (<70) as opposed to 2% to 4% of controls. Preterm children with and without brain injury required more school services (76% and 44% vs 16%), and support in reading (44% and 28% vs 9%), writing (44% and 20% vs 4%), and mathematics (47% and 30% vs 6%) compared with controls. Preterm children also displayed more behavior problems than their term counterparts. Severe neonatal brain injury was the strongest predictor of poor intelligence. Antenatal steroids, higher maternal education, and 2-parent family were associated with better cognition, whereas minority status incurred a disadvantage. Indomethacin did not affect intellectual function among preterm children. CONCLUSIONS. Preterm children born in the early 1990s, especially those with severe brain injury, demonstrate serious deficits in their neuropsychological profile, which translates into increased use of school services at 12 years.

OBJECTIVE. Although preterm very low birth weight infants have a high prevalence of neuroanatomical abnormalities when evaluated at term-equivalent age, patterns of brain growth in prematurely born infants during school age and adolescence remain largely unknown. Our goal was to test the hypothesis that preterm birth results in long-term dynamic changes in the developing brain. METHODS. We performed serial volumetric MRI studies at ages 8 and 12 years in 55 preterm infants born weighing 600 to 1250 g and 20 term control children who participated in the follow-up component of a prospective, randomized, placebo-controlled intraventricular hemorrhage prevention study. RESULTS. Total brain volumes increased 2% to 3% between the ages of 8 and 12 years for both preterm and term children. These changes involved reductions in cerebral gray matter while white matter increased. Between 8 and 12 years of age, preterm subjects experienced a 2% decrease in left cerebral gray matter compared with a 10% reduction in left cerebral gray for term controls. For right cerebral gray matter, preterm children experienced a 3% decrease in volume between years 8 and 12, compared with 9% for term controls (group-by-time). In contrast, preterm subjects had a 10% increase in cerebral white matter volumes bilaterally between ages 8 and 12 years, compared with >26% increases for both hemispheres for term controls. Significant differences in regional volume changes between study groups were found in bilateral temporal gray and in parietal white matter. CONCLUSIONS. Preterm birth continues to perturb the trajectory of cerebral development during late childhood and early adolescence with preterm children, showing both lower gray matter reduction and less white matter gain over time compared with term control subjects.

Recent data suggest recovery of language systems but persistent structural abnormalities in the prematurely born. We tested the hypothesis that subjects who were born prematurely develop alternative networks for processing language. Subjects who were born prematurely (n = 22; 600-1250 g birth weight), without neonatal brain injury on neonatal cranial ultrasound, and 26 term control subjects were examined with a functional magnetic resonance imaging (fMRI) semantic association task, the Wechsler Intelligence Scale for Children-III (WISC-III) and the Clinical Evaluation of Language Fundamentals (CELF). In-magnet task accuracy and response times were calculated, and fMRI data were evaluated for the effect of group on blood oxygen level dependent (BOLD) activation, the correlation between task accuracy and activation and the functional connectivity between regions activating to task. Although there were differences in verbal IQ and CELF scores between the preterm (PT) and term control groups, there were no significant differences for either accuracy or response time for the in-magnet task. Both groups activated classic semantic processing areas including the left superior and middle temporal gyri and inferior frontal gyrus, and there was no significant difference in activation patterns between groups. Clear differences between the groups were observed in the correlation between task accuracy and activation to task at P < 0.01, corrected for multiple comparisons. Left inferior frontal gyrus correlated with accuracy only for term controls and left sensory motor areas correlated with accuracy only for PT subjects. Left middle temporal gyri correlated with task accuracy for both groups. Connectivity analyses at P < 0.001 revealed the importance of a circuit between left middle temporal gyri and inferior frontal gyrus for both groups. In addition, the PT subjects evidenced greater connectivity between traditional language areas and sensory motor areas but significantly fewer correlated areas within the frontal lobes when compared to term controls. We conclude that at 12 years of age, children born prematurely and children born at term had no difference in performance on a simple lexical semantic processing task and activated similar areas. Connectivity analyses, however, suggested that PT subjects rely upon different neural pathways for lexical semantic processing when compared to term controls. Plasticity in network connections may provide the substrate for improving language skills in the prematurely born.

OBJECTIVES: To more precisely examine regional and subregional microstructural brain changes associated with preterm birth. STUDY DESIGN: We obtained brain volumes from 29 preterm children, age 12 years, with no ultrasound scanning evidence of intraventricular hemorrhage or cystic periventricular leukomalacia in the newborn period, and 22 age- and sex-matched term control subjects. RESULTS: Preterm male subjects demonstrated significantly lower white matter volumes in bilateral cingulum, corpus callosum, corticospinal tract, prefrontal cortex, superior and inferior longitudinal fasciculi compared with term male subjects. Gray matter volumes in prefrontal cortex, basal ganglia, and temporal lobe also were significantly reduced in preterm male subjects. Brain volumes of preterm female subjects were not significantly different from those of term female control subjects. Voxel-based morphometry results were not correlated with perinatal variables or cognitive outcome. Higher maternal education was associated with higher cognitive performance in preterm male subjects. CONCLUSIONS: Preterm male children continue to demonstrate abnormal neurodevelopment at 12 years of age. However, brain morphology in preterm female children may no longer differ from that of term female children. The neurodevelopmental abnormalities we detected in preterm male subjects appear to be relatively diffuse, involving multiple neural systems. The relationship between aberrant neurodevelopment and perinatal variables may be mediated by genetic factors, environmental factors, or both reflected in maternal education level.

OBJECTIVE. The goal was to use diffusion tensor imaging to test the hypothesis that prematurely born children demonstrate long-term, white matter, microstructural differences, relative to term control subjects. METHODS. Twenty-nine preterm subjects (birth weight: 600-1250 g) without neonatal brain injury and 22 matched, term, control subjects were evaluated at 12 years of age with MRI studies, including diffusion tensor imaging and volumetric imaging; voxel-based morphometric strategies were used to corroborate regional diffusion tensor imaging results. Subjects also underwent neurodevelopmental assessments. RESULTS. Neurodevelopmental assessments showed significant differences in full-scale, verbal, and performance IQ and Developmental Test of Visual Motor Integration scores between the preterm and term control subjects. Diffusion tensor imaging studies demonstrated widespread decreases in fractional anisotropy (a measure of fiber tract organization) in the preterm children, compared with the control subjects. Regions included both intrahemispheric association fibers subserving language skills, namely, the right inferior frontooccipital fasciculus and anterior portions of the uncinate fasciculi bilaterally, and the deep white matter regions to which they project, as well as the splenium of the corpus callosum. These changes in fractional anisotropy occurred in subjects with significant differences in frontal, temporal, parietal, and deep white matter volumes. Fractional anisotropy values in the left anterior uncinate correlated with verbal IQ, full-scale IQ, and Peabody Picture Vocabulary Test-Revised scores for preterm male subjects. In addition, preterm male subjects were found to have the lowest values for fractional anisotropy in the right anterior uncinate fasciculus, and fractional anisotropy values in that region correlated with both verbal IQ and Peabody Picture Vocabulary Test-Revised scores for the preterm groups; these findings were supported by changes identified with voxel-based morphometric analyses. CONCLUSIONS. Compared with term control subjects, prematurely born children with no neonatal ultrasound evidence of white matter injury manifest changes in neural connectivity at 12 years of age.