Intellectual Functioning of Children With Isolated PRS, PRS-Plus, and Syndromic PRS.

OBJECTIVE: Describe the intelligence quotient (IQ) of children with Pierre Robin sequence (PRS). DESIGN: Prospective cohort study. SETTING: Neurodevelopmental follow-up clinic within a hospital. PATIENTS: Children with PRS (n = 45) who had been in the Neonatal Intensive Care Unit (NICU) were classified by a geneticist into 3 subgroups of isolated PRS (n = 20), PRS-plus additional medical features (n = 8), and syndromic PRS (n = 17) based on medical record review and genetic testing. MAIN OUTCOME MEASURE: Children with PRS completed IQ testing at 5 or 8 years of age with the Wechsler Preschool and Primary Scale of Intelligence, Third Edition (WPPSI-III) or Fourth Edition (WPPSI-IV) or the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) or Fifth Edition (WISC-V). RESULTS: IQ scores were more than 1 to 2 standard deviations below the mean for 36% of the overall sample, which was significantly greater compared to test norms (binomial test P = .001). There was a significant association between PRS subtype and IQ (Fisher's exact P = .026). While only 20% of children with isolated PRS were within 1 standard deviation below average and 35% of children with syndromic PRS were below 1 to 2 standard deviations, 75% of PRS-plus children scored lower than 1 to 2 standard deviations below the mean. CONCLUSION: PRS subgroups can help identify children at risk for cognitive delay. The majority of children with PRS-plus had low intellectual functioning, in contrast to the third of children with syndromic PRS who had low IQ and the majority of children with isolated PRS who had average or higher IQ.

Mental health in young adults born extremely preterm or extremely low birthweight with contemporary neonatal intensive care.

BACKGROUND: For infants born in the contemporary era of neonatal care, little is known about adult mental health outcomes of extremely preterm birth (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g). This study aimed to compare attention deficit hyperactivity disorder (ADHD), anxiety, mood, and substance use disorder prevalence in young adults born EP/ELBW and normal birthweight (NBW; >2499 g) controls, and to compare change in prevalence of mental health symptoms and disorders from 18 to 25 years. METHODS: Participants were a prospective geographical cohort of 297 consecutive survivors born EP/ELBW during 1991-1992 and 260 NBW controls. At age 25 years, 174 EP/ELBW and 139 NBW participants completed the Adult ADHD Rating Scale, Structured Clinical Interview for DSM-IV Disorders, Beck Anxiety Inventory, and Center for Epidemiologic Studies Depression Scale-Revised. Data from follow-up at 18 years were also utilized. Multiple imputation was used to account for attrition. RESULTS: Mental health outcomes at 25 years were similar between groups: prevalence rates were ADHD 7% v. 5%; anxiety 32% v. 27%; mood 38% v. 35%; substance use 12% v. 14% in the EP/ELBW and NBW groups, respectively. In both groups, ADHD declined between 18 and 25 years [odds ratio (OR) per year = 0.87, 95% confidence interval (CI) 0.79-0.95], and generalized anxiety disorder and major depressive episode became more common (OR 1.22, 95% CI 1.10-1.35 per year; OR 1.20, 95% CI 1.10-1.30 respectively). CONCLUSIONS: This contemporary EP/ELBW cohort has comparable young adult mental health outcomes to controls, and similar patterns of change in mental health from late adolescence.

Episodic and prospective memory difficulties in 13-year-old children born very preterm.

OBJECTIVES: Children born very preterm (VP) are susceptible to a range of cognitive impairments, yet the effects of VP birth on long-term, episodic, and prospective memory remains unclear. This study examined episodic and prospective memory functioning in children born VP compared with their term-born counterparts at 13 years. METHOD: VP (n = 81: born <30 weeks' gestation) and term (n = 26) groups were aged between 12 and 14 years. Children completed: (i) standardized verbal and visuospatial episodic memory tests; and (ii) an experimental time- and event-based prospective memory test that included short-term (within assessment session) and long-term (up to 1-week post-session) tasks. Parents completed a questionnaire assessing memory functions in everyday life. RESULTS: The VP group performed worse on all measures of verbal and visuospatial episodic memory than the term group. While there were no group differences in event-based or long-term prospective memory, the VP group performed worse on time-based and short-term prospective memory tasks than term-born counterparts. Parents of children born VP reported more everyday memory difficulties than parents of children born at term, with parent-ratings indicating significantly elevated rates of everyday memory challenges in children born VP. CONCLUSIONS: Children born VP warrant long-term surveillance, as challenges associated with VP birth include memory difficulties at 13 years. This study highlights the need for greater research and clinical attention into childhood functional memory outcomes.

Motor performance and attention outcomes in children born very preterm.

AIM: To examine the relationship between motor performance and attention in children born very preterm and at term, and investigate the presence of individual profiles of motor and attention performance. METHOD: Attention and motor performance at 7 and 13 years were assessed in 197 children born very preterm (52.5% male) and 69 children born at term (47.8% male) between 2001 and 2003. Linear regression models were fitted including an interaction term for birth group. Subgroups of children with similar attention and motor performance profiles were identified using latent profile analysis. RESULTS: Balance was positively associated with all attention outcomes at both ages (p < 0.006). There were specific birth group interactions for aiming and catching and manual dexterity with attention at 13 years, with positive associations observed only for children born very preterm (p < 0.001). At 7 years, three profiles were observed: average attention and motor functioning; average motor functioning and low attention functioning; and low attention and motor functioning. At 13 years, two profiles of average attention and motor functioning emerged, as well as one profile of below-average attention and motor functioning. Children born very preterm were overrepresented in the lower functioning profiles (born very preterm 56%; born at term 29%). INTERPRETATION: Motor functioning at age 7 years may be a useful marker of later attention skills, particularly for children born very preterm who are at greater risk of poorer long-term cognitive outcomes. WHAT THIS PAPER ADDS: Balance was positively associated with attention in children born very preterm and at term. Relationships between motor performance and attention at age 13 years differed between children born very preterm and at term. Heterogeneous motor functioning and attention outcomes were noted for children born very preterm and at term. Children born very preterm were more likely to have lower attention and motor functioning profiles than children born at term. There was greater movement in motor functioning and attention profiles between the ages of 7 and 13 years in children born very preterm.

Thirteen-Year Outcomes of a Randomized Clinical Trial of Early Preventive Care for Very Preterm Infants and Their Parents.

OBJECTIVE: To evaluate 13-year outcomes of a randomized controlled trial of preventive care (VIBeS Plus) for infants born very preterm and their parents and examine whether possible effects of intervention varied by family social risk. STUDY DESIGN: Families were randomized to an intervention arm (n = 61) or a standard care arm (n = 59). The intervention was delivered at home by psychologists and physiotherapists over the infants' first year, focusing on infant development and parental mental health. At 13 years corrected age, cognitive, motor, and behavioral outcomes, and parental mental health were assessed. Primary estimands were between-group mean differences, estimated using multiple imputed regression models. RESULTS: Follow-up included 81 surviving children (69%). There was little evidence of benefits of the intervention for IQ, attention, executive functioning, working memory, and academic skills regardless of level of social risk. Specifically, mean differences in adolescent cognitive outcomes ranged from -2.0 units (95% CI, -9.9 to 5.9) in favor of standard treatment to 5.1 units (95% CI, -2.3 to 12.5) favoring the intervention. A group-by-social risk interaction was observed only for adolescent motor outcomes, with mean differences favoring the intervention for those at higher social risk (balance, 4.9; 95% CI, 1.3-8.5; total motor, 3.2; 95% CI, 0.3-6.2), but not those at lower social risk (balance, -0.3; 95% CI, -2.4 to 1.9; total motor, 0.03; 95% CI, -1.9 to 2.0). Mean differences in adolescent behavior and parental mental health ranged from -6.6 (95% CI -13.8, 0.5) to -0.2 (95% CI, -1.9 to 1.4) and -1.8 (95% CI, -4.1 to 0.6) to -1.7 (95% CI, -4.3 to 1.0), respectively, indicating a pattern of fewer symptoms in the intervention group. CONCLUSIONS: Benefits of the intervention persisted for adolescent behavior, with better motor outcomes observed in those from socially disadvantaged families. Replication with larger samples, multiple informant reports, and assessment of quality of life-related outcomes is warranted. TRIAL REGISTRATION: http://www.anzctr.org.au/: ACTRN12605000492651.

Development of regional brain gray matter volume across the first 13 years of life is associated with childhood math computation ability for children born very preterm and full term.

Very preterm birth (VP; <32 weeks' gestation) is associated with altered brain gray matter development and lower math ability. In typically developing children, the neural correlates of math ability may change dynamically with age, though evidence in VP children is limited. In a prospective longitudinal cohort of children born VP and full term (FT), we aimed to investigate associations between 1) concurrent regional brain volumes and math ability at 7 (n = 148 VP; n = 34 FT) and 13-years (n = 130 VP; n = 46 FT), and 2) regional volumetric growth across childhood (term-equivalent age (TEA) to 7-years; 7 to 13-years) and math ability from 7 to 13-years, and improvement in ability from 7 to 13 years. For both aims we investigated whether associations differed between birth groups. Cross-sectionally, frontal, temporal and subcortical regional volumes were positively associated with math ability for both birth groups. For FT children, greater growth of specific temporal regions was associated with higher math ability, and greater improvements. For VP children, similar associations were only observed for growth from TEA to 7-years with 13-year ability and improvements in ability. In conclusion, VP birth appears to alter associations of brain development across the first 13 years with childhood math ability.

Missing out on precious time: Extending paid parental leave for parents of babies admitted to neonatal intensive or special care units for prolonged periods.

In Australia, approximately 18% of newborn babies are admitted to a neonatal intensive or special care nursery. While most babies admitted to a neonatal intensive or special care nursery are discharged home within a few weeks, around 6% of babies spend more than 2 weeks in hospital. For the parents of these babies, much of their leave entitlements (Australian Government Paid Parental Leave Scheme is up to18 weeks for the primary care giver and up to 2 weeks for partners) are used before their baby comes home from hospital. The time babies and parents spend together in the early developmental period, during the hospitalisation and when the baby is discharged home, is crucial for optimal child development and bonding. Yet care givers who have a baby admitted to neonatal intensive or special care for extended periods are not currently entitled to any extra parental leave payments in Australia. We recommend the Australian Paid Parental Leave Act is changed to allow primary carers access to 1 week of extra parental leave pay for every week in hospital (for babies admitted to hospital for more than 2 weeks), up to a maximum of 14 weeks. For fathers and partners of these babies, we recommend an additional 2 weeks of extra Dad and Partner Pay. The net cost, taking into account likely productivity benefits, would be less than 1.5% of the current cost of the scheme and would improve health and socio-economic outcomes for the baby, family and society.

Rates of Developmental Coordination Disorder in Children Born Very Preterm.

OBJECTIVE: To examine the stability of developmental coordination disorder (DCD) throughout childhood in children born very preterm and term. Further, in the very preterm group, to compare perinatal variables and neurobehavioral outcomes at 13 years of age for children with persisting DCD and those with typical motor development. STUDY DESIGN: Prospective study of 180 very preterm and 73 term-born children assessed at 5, 7, and/or 13 years of age using the Movement Assessment Battery for Children, with scores ≤16th percentile used to classify DCD. Children with cerebral palsy or an IQ of <80 were excluded. RESULTS: Children born very preterm had increased odds for DCD at 5 (OR, 5.53; 95% CI, 2.53-12.0; P < .001), 7 (OR, 3.63; 95% CI, 1.43-9.18; P = .06), and 13 years (OR, 4.34; 95% CI, 1.61-11.7; P = .004) compared with term-born children. The rates of DCD in very preterm children reduced from 47.9% at 5 years of age, to 28.5% at 7 years and 27.8% at 13 years of age (OR per year of age, 0.81; 95% CI, 0.75-0.87; P < .001), but less so for term-born children (15.3%, 10.0%, and 8.5% at 5, 7, and 13-years respectively [OR, 0.91; 95% CI, 0.75-1.09; P = .31]). Within the very preterm group at 13 years of age, there was evidence that children with persisting DCD performed poorer across several cognitive domains compared with children with typical motor development, with differences in the order of 0.5-1.0 SD. CONCLUSIONS: Although the rates of DCD decreased across middle childhood for both groups, the odds for DCD were consistently higher for very preterm children compared with term, with important implications for cognitive functioning in the very preterm group.

Individual Attention Patterns in Children Born Very Preterm and Full Term at 7 and 13 Years of Age.

OBJECTIVE: To identify attention profiles at 7 and 13 years, and transitions in attention profiles over time in children born very preterm (VP; <30 weeks' gestation) and full term (FT), and examine predictors of attention profiles and transitions. METHODS: Participants were 167 VP and 60 FT children, evaluated on profiles across five attention domains (selective, shifting and divided attention, processing speed, and behavioral attention) at 7 and 13 years using latent profile analyses. Transitions in profiles were assessed with contingency tables. For VP children, biological and social risk factors were tested as predictors with a multinomial logistic regression. RESULTS: At 7 and 13 years, three distinct profiles of attentional functioning were identified. VP children were 2-3 times more likely to show poorer attention profiles compared with FT children. Transition patterns between 7 and 13 years were stable average, stable low, improving, and declining attention. VP children were two times less likely to have a stable average attention pattern and three times more likely to have stable low or improving attention patterns compared with FT children. Groups did not differ in declining attention patterns. For VP children, brain abnormalities on neonatal MRI and greater social risk at 7 years predicted stable low or changing attention patterns over time. CONCLUSIONS: VP children show greater variability in attention profiles and transition patterns than FT children, with almost half of the VP children showing adverse attention patterns over time. Early brain pathology and social environment are markers for attentional functioning.

Early environment and long-term outcomes of preterm infants.

Prematurity is associated with an increased risk of long-term health and neurodevelopmental problems. Key perinatal and neonatal factors that affect these outcomes have long been studied. However, more recently, there has been an appreciation of the importance of environmental factors in long-term outcomes of preterm babies, particularly in light of the rapid maturation of the brain during these babies' early days of life. Breastmilk and breastfeeding is the gold standard for infant feeding, including preterm babies. The benefits are well established in regard to protection from serious complications like necrotising enterocolitis. Although theoretically plausible, the benefits for neurodevelopment are less clear. Noise, pain and the environment of the neonatal intensive care can also affect infant neurodevelopment. It is established that noise and pain have deleterious effects. However, the benefits of single-room vs open-bay neonatal units remain under debate. Developmental care practices, of which there are many, are increasingly embraced worldwide. There are benefits both for the parents and the baby, however, the evidence is difficult to pool due to the heterogeneity of studies and study populations. Finally, it is important to remember the importance of the role of parents in shaping long-term neurodevelopment of the high-risk preterm newborn. Increasingly, positive parenting and parents' mental health are shown to have long lasting advantages for preterm infants. A deeper understanding of early environmental factors is key to developing future interventions to optimise outcomes of preterm newborns.

Epigenetic Influences on Neurodevelopment at 11 Years of Age: Protocol for the Longitudinal Peri/Postnatal Epigenetic Twins Study at 11 Years of Age (PETS@11).

Neurodevelopment is sensitive to genetic and pre/postnatal environmental influences. These effects are likely mediated by epigenetic factors, yet current knowledge is limited. Longitudinal twin studies can delineate the link between genetic and environmental factors, epigenetic state at birth and neurodevelopment later in childhood. Building upon our study of the Peri/postnatal Epigenetic Twin Study (PETS) from gestation to 6 years of age, here we describe the PETS 11-year follow-up in which we will use neuroimaging and cognitive testing to examine the relationship between early-life environment, epigenetics and neurocognitive outcomes in mid-childhood. Using a within-pair twin model, the primary aims are to (1) identify early-life epigenetic correlates of neurocognitive outcomes; (2) determine the developmental stability of epigenetic effects and (3) identify modifiable environmental risk factors. Secondary aims are to identify factors influencing gut microbiota between 6 and 11 years of age to investigate links between gut microbiota and neurodevelopmental outcomes in mid-childhood. Approximately 210 twin pairs will undergo an assessment at 11 years of age. This includes a direct child cognitive assessment, multimodal magnetic resonance imaging, biological sampling, anthropometric measurements and a range of questionnaires on health and development, behavior, dietary habits and sleeping patterns. Data from complementary data sources, including the National Assessment Program - Literacy and Numeracy and the Australian Early Development Census, will also be sought. Following on from our previous focus on relationships between growth, cardiovascular health and oral health, this next phase of PETS will significantly advance our understanding of the environmental interactions that shape the developing brain.

Hand Preference and Cognitive, Motor, and Behavioral Functioning in 10-Year-Old Extremely Preterm Children.

The association of hand preference (left, mixed, and right) with cognitive, academic, motor, and behavioral function was evaluated in 864 extremely preterm children at 10 years of age. Left-handed and right-handed children performed similarly but mixed-handed children had greater odds of functional deficits across domains than right-handed children.

Language Trajectories of Children Born Very Preterm and Full Term from Early to Late Childhood.

OBJECTIVE: To identify distinct language trajectories of children born very preterm and full term from 2 to 13 years of age and examine predictors for the identified trajectories. STUDY DESIGN: A cohort of 224 children born very preterm and 77 full term controls recruited at birth were followed up at ages 2, 5, 7, and 13 years. The number of distinct language trajectories was examined using latent growth mixture modeling allowing for linear and quadratic time trends. Potential predictors in the neonatal period (eg, birth group, sex, and medical risk) and at 2 years (ie, social risk and use of allied health services) for the language trajectories were tested using multinomial logistic regression. RESULTS: Five distinct language trajectories were identified across childhood: stable normal (32% of study cohort), resilient development showing catch-up (36%), precocious language skills (7%), stable low (17%), and high-risk (5%) development. The very preterm group was 8 times more likely to have a language trajectory that represented poorer language development compared with full term controls (very preterm, 40%; full term, 6%). Greater social risk and use of allied health services were associated with poorer language development. CONCLUSIONS: Variable language trajectories were observed, with a substantial proportion of children born very preterm exhibiting adverse language development. These findings highlight the need for monitoring language skills in children born very preterm before school entry and across middle childhood.

Goal Setting Deficits at 13 Years in Very Preterm Born Children.

OBJECTIVES: Preterm children demonstrate deficits in executive functions including inhibition, working memory, and cognitive flexibility; however, their goal setting abilities (planning, organization, strategic reasoning) remain unclear. This study compared goal setting abilities between very preterm (VP: <30 weeks/<1250 grams) and term born controls during late childhood. Additionally, early risk factors (neonatal brain abnormalities, medical complications, and sex) were examined in relationship to goal setting outcomes within the VP group. METHODS: Participants included 177 VP and 61 full-term born control children aged 13 years. Goal setting was assessed using several measures of planning, organization, and strategic reasoning. Parents also completed the Behavior Rating Inventory of Executive Function. Regression models were performed to compare groups, with secondary analyses adjusting for potential confounders (sex and social risk), and excluding children with major neurosensory impairment and/or IQ<70. Within the VP group, regression models were performed to examine the relationship between brain abnormalities, medical complications, and sex, on goal setting scores. RESULTS: The VP group demonstrated a clear pattern of impairment and inefficiency across goal setting measures, consistent with parental report, compared with their full-term born peers. Within the VP group, moderate/severe brain abnormalities on neonatal MRI predicted adverse goal setting outcomes at 13. CONCLUSIONS: Goal setting difficulties are a significant area of concern in VP children during late childhood. These difficulties are associated with neonatal brain abnormalities, and are likely to have functional consequences academically, socially and vocationally. (JINS, 2018, 24, 372-381).

Brain Volumes at Term-Equivalent Age Are Associated with 2-Year Neurodevelopment in Moderate and Late Preterm Children.

OBJECTIVE: To explore the association between brain maturation, injury, and volumes at term-equivalent age with 2-year development in moderate and late preterm children. STUDY DESIGN: Moderate and late preterm infants were recruited at birth and assessed at age 2 years using the Bayley Scales of Infant and Toddler Development, Third Edition. Brain magnetic resonance imaging (MRI) was performed at term-equivalent age and qualitatively assessed for brain maturation (myelination of the posterior limb of the internal capsule and gyral folding) and injury. Brain volumes were measured using advanced segmentation techniques. The associations between brain MRI measures with developmental outcomes were explored using linear regression analyses. RESULTS: A total of 197 children underwent MRI and assessed using the Bayley Scales of Infant and Toddler Development, Third Edition. Larger total brain tissue volumes were associated with higher cognitive and language scores (adjusted coefficients per 10% increase in brain size; 95% CI of 3.2 [0.4, 5.6] and 5.6 [2.4, 8.8], respectively). Similar relationships were documented for white matter volumes with cognitive and language scores, multiple cerebral structures with language scores, and cerebellar volumes with motor scores. Larger cerebellar volumes were independently associated with better language and motor scores, after adjustment for other perinatal factors. There was little evidence of relationships between myelination of the posterior limb of the internal capsule, gyral folding, or injury with 2-year development. CONCLUSIONS: Larger total brain tissue, white matter, and cerebellar volumes at term-equivalent age are associated with better neurodevelopment in moderate and late preterm children. Brain volumes may be an important marker for neurodevelopmental deficits described in moderate and late preterm children.

Altered posterior cingulate brain metabolites and cognitive dysfunction in preterm adolescents.

BACKGROUND: Extremely preterm (EP, <28 wk gestation) individuals have increased the risk of cognitive deficits compared with controls. The posterior cingulate region has an important role in cognitive function, but how this is affected by preterm birth is unknown. We aimed to compare brain metabolite ratios of neurons and cell membranes between EP 18-y olds and controls, and explore the association between metabolite ratios and cognitive outcomes. METHOD: A regional cohort of 150 EP and 134 controls were recruited for the study. Cerebral metabolites were measured using proton magnetic resonance spectroscopy (MRS) obtained from a left posterior cingulate voxel. Total N-acetylaspartate (tNAA, neuronal marker)/total creatine (tCr), and total choline (tCho, cell membrane marker)/tCr ratios were compared between groups using linear regression. Metabolite ratios were correlated with tests of general intelligence (IQ), memory, and attention using linear or logistic regression. RESULTS: Compared with controls, EP had lower tNAA/tCr (mean difference (95% CI) of -2.27% (-4.09, -0.45)) and tCho/tCr (mean difference (95% CI) of -11.11% (-20.37, -1.85)), all P = 0.02. Higher tCho/tCr correlated with better IQ in the EP group only; whereas higher tNAA/tCr ratios correlated with better scores in working memory and attention in both groups. CONCLUSION: EP birth is associated with long-term brain metabolite ratio alterations. This may underlie poorer cognitive performance in EP survivors.

Abnormalities in orbitofrontal cortex gyrification and mental health outcomes in adolescents born extremely preterm and/or at an extremely low birth weight.

Extremely preterm (EP, <28 weeks) and/or extremely low birth weight (ELBW, <1000 g) infants are at high risk of aberrant neurodevelopment. Sulcogyral folding patterns of the orbitofrontal cortex (OFC) are determined during the third trimester, however little is known about OFC patterning in EP/ELBW cohorts, for whom this gestational period is disturbed. This study investigated whether the distribution of OFC pattern types and frequency of intermediate and/or posterior orbital sulci (IOS/POS) differed between EP/ELBW and control adolescents. This study also investigated whether OFC pattern type was associated with mental illness or executive function outcome in adolescence. Magnetic resonance images of 194 EP/ELBW and 147 full term (>37 completed weeks) and/or normal birth weight (> 2500 g) adolescents were acquired, from which the OFC pattern of each hemisphere was classified as Type I, II, or III. Compared with controls, more EP/ELBW adolescents possessed a Type II in the left hemisphere (P = 0.019). The EP/ELBW group had fewer IOS (P = 0.024) and more POS (P = 0.021) in the left hemisphere compared with controls. OFC pattern type was not associated with mental illness, however in terms of executive functioning, Type III in the left hemisphere was associated with better parent-reported metacognition scores overall (P = 0.008) and better self-reported behavioral regulation scores in the control group (P = 0.001) compared with Type I. We show, for the first time that EP/ELBW birth is associated with changes in orbitofrontal development, and that specific patterns of OFC folding are associated with executive function at age 18 years in both EP/ELBW and control subjects.

Neurodevelopmental Outcomes and Neural Mechanisms Associated with Non-right Handedness in Children Born Very Preterm.

Non-right handedness (NRH) is reportedly more common in very preterm (VPT; <32 weeks' gestation) children compared with term-born peers, but it is unclear whether neonatal brain injury or altered brain morphology and microstructure underpins NRH in this population. Given that NRH has been inconsistently reported to be associated with cognitive and motor difficulties, this study aimed to examine associations between handedness and neurodevelopmental outcomes in VPT 7-year-olds. Furthermore, the relationship between neonatal brain injury and integrity of motor tracts (corpus callosum and corticospinal tract) with handedness at age 7 years in VPT children was explored. One hundred seventy-five VPT and 69 term-born children completed neuropsychological and motor assessments and a measure of handedness at 7 years' corrected age. At term-equivalent age, brain injury on MRI was assessed and diffusion tensor measures were obtained for the corpus callosum and posterior limb of the internal capsule. There was little evidence of stronger NRH in the VPT group compared with term controls (regression coefficient [b] -1.95, 95% confidence interval [-5.67, 1.77]). Poorer academic and working memory outcomes were associated with stronger NRH in the VPT group. While there was little evidence that neonatal unilateral brain injury was associated with stronger NRH, increased area and fractional anisotropy of the corpus callosum splenium were predictive of stronger NRH in the VPT group. VPT birth may alter the relationship between handedness and academic outcomes, and neonatal corpus callosum integrity predicts hand preference in VPT children at school age. (JINS, 2015, 21, 610-621).

Brain structural and microstructural alterations associated with cerebral palsy and motor impairments in adolescents born extremely preterm and/or extremely low birthweight.

AIM: To elucidate neurobiological changes underlying motor impairments in adolescents born extremely preterm (gestation <28wks) and/or with extremely low birthweight (ELBW, <1000g), our aims were the following: (1) to compare corticospinal tract (CST) microstructure and primary motor cortex (M1) volume, area, and thickness between extremely preterm/ELBW adolescents and a comparison group with normal birthweight (>2499g); (2) to compare CST microstructure and M1 volume, area, and thickness between extremely preterm/ELBW adolescents with cerebral palsy (CP), motor impairment without CP, and no motor impairment; and (3) to investigate associations between CST microstructure and M1 measures. METHOD: This study used diffusion and structural magnetic resonance imaging to examine the CST and M1 in a geographical cohort of 191 extremely preterm/ELBW adolescents (mean age 18y 2.4mo [SD 9.6mo]; 87 males, 104 females) and 141 adolescents in the comparison group (mean age 18y 1.2mo [SD 9.6mo]; 59 males, 82 females). RESULTS: Extremely preterm/ELBW adolescents had higher CST axial, radial, and mean diffusivities and lower M1 thickness than the comparison group. Extremely preterm/ELBW adolescents with CP had higher CST diffusivities than non-motor-impaired extremely preterm/ELBW adolescents. CST diffusivities correlated with M1 volume and area. INTERPRETATION: Extremely preterm/ELBW adolescents have altered CST microstructure, which is associated with CP. Furthermore, the results elucidate how CST and M1 alterations interrelate to potentially influence motor function in extremely preterm/ELBW adolescents.