Low to moderate prenatal alcohol exposure and neurodevelopment in a prospective cohort of early school aged children.

Evidence is strong for adverse fetal effects of high level or chronic prenatal alcohol exposure (PAE), but many pregnant women continue to drink at lower levels. The 'Asking Questions about Alcohol in pregnancy' prospective cohort aimed to determine the neurodevelopmental consequences at 6-8 years of age of low to moderate PAE. 1570 women from seven public antenatal clinics in Melbourne, Australia, provided information on frequency and quantity of alcohol use, and obstetric, lifestyle and socio-environmental confounders at four gestation timepoints. PAE was classified into five trajectories plus controls. At 6-8 years, 802 of 1342 eligible families took part and completed a questionnaire (60%) and 696 children completed neuropsychological assessments (52%). Multiple linear regressions examined mean outcome differences between groups using complete case and multiple imputation models. No meaningful relationships were found between any of the PAE trajectories and general cognition, academic skills, motor functioning, behaviour, social skills, social communication, and executive function. Maternal education most strongly influenced general cognition and academic skills. Parenting behaviours and financial situation were associated with academic skills, behaviour, social skills and/or executive function. The lack of association between PAE and neurodevelopment at 6-8 years may partly be explained by cumulative positive effects of socio-environmental factors.

Updates to the Melbourne Children's Regional Infant Brain Software Package (M-CRIB-S).

The delineation of cortical areas on magnetic resonance images (MRI) is important for understanding the complexities of the developing human brain. The previous version of the Melbourne Children's Regional Infant Brain (M-CRIB-S) (Adamson et al. Scientific Reports, 10(1), 10, 2020) is a software package that performs whole-brain segmentation, cortical surface extraction and parcellation of the neonatal brain. Available cortical parcellation schemes in the M-CRIB-S are the adult-compatible 34- and 31-region per hemisphere Desikan-Killiany (DK) and Desikan-Killiany-Tourville (DKT), respectively. We present a major update to the software package which achieves two aims: 1) to make the voxel-based segmentation outputs derived from the Freesurfer-compatible M-CRIB scheme, and 2) to improve the accuracy of whole-brain segmentation and cortical surface extraction. Cortical surface extraction has been improved with additional steps to improve penetration of the inner surface into thin gyri. The improved cortical surface extraction is shown to increase the robustness of measures such as surface area, cortical thickness, and cortical volume.

Associations between low-moderate prenatal alcohol exposure and brain development in childhood.

BACKGROUND: The effects of low-moderate prenatal alcohol exposure (PAE) on brain development have been infrequently studied. AIM: To compare cortical and white matter structure between children aged 6 to 8 years with low-moderate PAE in trimester 1 only, low-moderate PAE throughout gestation, or no PAE. METHODS: Women reported quantity and frequency of alcohol consumption before and during pregnancy. Magnetic resonance imaging was undertaken for 143 children aged 6 to 8 years with PAE during trimester 1 only (n = 44), PAE throughout gestation (n = 58), and no PAE (n = 41). T1-weighted images were processed using FreeSurfer, obtaining brain volume, area, and thickness of 34 cortical regions per hemisphere. Fibre density (FD), fibre cross-section (FC) and fibre density and cross-section (FDC) metrics were computed for diffusion images. Brain measures were compared between PAE groups adjusted for age and sex, then additionally for intracranial volume. RESULTS: After adjustments, the right caudal anterior cingulate cortex volume (pFDR = 0.045) and area (pFDR = 0.008), and right cingulum tract cross-sectional area (pFWE < 0.05) were smaller in children exposed to alcohol throughout gestation compared with no PAE. CONCLUSION: This study reports a relationship between low-moderate PAE throughout gestation and cingulate cortex and cingulum tract alterations, suggesting a teratogenic vulnerability. Further investigation is warranted.

Cortical growth from infancy to adolescence in preterm and term-born children.

Early life experiences can exert a significant influence on cortical and cognitive development. Very preterm birth exposes infants to several adverse environmental factors during hospital admission, which affect cortical architecture. However, the subsequent consequence of very preterm birth on cortical growth from infancy to adolescence has never been defined; despite knowledge of critical periods during childhood for establishment of cortical networks. Our aims were to: chart typical longitudinal cortical development and sex differences in cortical development from birth to adolescence in healthy term-born children; estimate differences in cortical development between children born at term and very preterm; and estimate differences in cortical development between children with normal and impaired cognition in adolescence. This longitudinal cohort study included children born at term (≥37 weeks' gestation) and very preterm (<30 weeks' gestation) with MRI scans at ages 0, 7 and 13 years (n = 66 term-born participants comprising 34 with one scan, 18 with two scans and 14 with three scans; n = 201 very preterm participants comprising 56 with one scan, 88 with two scans and 57 with three scans). Cognitive assessments were performed at age 13 years. Cortical surface reconstruction and parcellation were performed with state-of-the-art, equivalent MRI analysis pipelines for all time points, resulting in longitudinal cortical volume, surface area and thickness measurements for 62 cortical regions. Developmental trajectories for each region were modelled in term-born children, contrasted between children born at term and very preterm, and contrasted between all children with normal and impaired cognition. In typically developing term-born children, we documented anticipated patterns of rapidly increasing cortical volume, area and thickness in early childhood, followed by more subtle changes in later childhood, with smaller cortical size in females than males. In contrast, children born very preterm exhibited increasingly reduced cortical volumes, relative to term-born children, particularly during ages 0-7 years in temporal cortical regions. This reduction in cortical volume in children born very preterm was largely driven by increasingly reduced cortical thickness rather than area. This resulted in amplified cortical volume and thickness reductions by age 13 years in individuals born very preterm. Alterations in cortical thickness development were found in children with impaired language and memory. This study shows that the neurobiological impact of very preterm birth on cortical growth is amplified from infancy to adolescence. These data further inform the long-lasting impact on cortical development from very preterm birth, providing broader insights into neurodevelopmental consequences of early life experiences.

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.

Long-lasting effects of very preterm birth on brain structure in adulthood: A systematic review and meta-analysis.

Early life experiences, such as very preterm (VP) birth, can affect brain and cognitive development. Several prior studies investigated brain structure in adults born VP; synthesising these studies may help to provide a clearer understanding of long-term effects of VP birth on the brain. We systematically searched Medline and Embase for articles that investigated brain structure using MRI in adulthood in individuals born VP (<32 weeks' gestation) or with very low birth weight (VLBW; <1500 g), and controls born at term or with normal birth weight. In total, 77 studies met the review inclusion criteria, of which 28 studies were eligible for meta-analyses, including data from up to 797 VP/VLBW participants and 518 controls, aged 18-33 years. VP/VLBW adults exhibited volumetric, morphologic and microstructural alterations in subcortical and temporal cortical regions compared with controls, with pooled standardised mean differences up to - 1.0 (95% confidence interval: -1.2, -0.8). This study suggests there is a persisting neurological impact of VP birth, which may provide developmental neurobiological insights for adult cognition in high-risk populations.

Fiber-Specific Measures of White Matter Microstructure and Macrostructure Are Associated With Internalizing and Externalizing Symptoms in Children Born Very Preterm and Full-term.

BACKGROUND: Tensor-based investigations suggest that delayed or disrupted white matter development may relate to adverse behavioral outcomes in individuals born very preterm (VP); however, metrics derived from such models lack specificity. Here, we applied a fixel-based analysis framework to examine white matter microstructural and macrostructural correlates of concurrent internalizing and externalizing problems in VP and full-term (FT) children at 7 and 13 years. METHODS: Diffusion imaging data were collected in a longitudinal cohort of VP and FT individuals (130 VP and 29 FT at 7 years, 125 VP and 44 FT at 13 years). Fixel-based measures of fiber density, fiber-bundle cross-section, and fiber density and cross-section were extracted from 21 white matter tracts previously implicated in psychopathology. Internalizing and externalizing symptoms were assessed using the Strengths and Difficulties Questionnaire parent report at 7 and 13 years. RESULTS: At age 7 years, widespread reductions in fiber-bundle cross-section and fiber density and cross-section and tract-specific reductions in fiber density were related to more internalizing and externalizing symptoms irrespective of birth group. At age 13 years, fixel-based measures were not related to internalizing symptoms, while tract-specific reductions in fiber density, fiber-bundle cross-section, and fiber density and cross-section measures were related to more externalizing symptoms in the FT group only. CONCLUSIONS: Age-specific neurobiological markers of internalizing and externalizing problems identified in this study extend previous tensor-based findings to inform pathophysiological models of behavior problems and provide the foundation for investigations into novel preventative and therapeutic interventions to mitigate risk in VP and other high-risk infant populations.

Growth of prefrontal and limbic brain regions and anxiety disorders in children born very preterm.

BACKGROUND: Children born very preterm (VP) display altered growth in corticolimbic structures compared with full-term peers. Given the association between the cortiocolimbic system and anxiety, this study aimed to compare developmental trajectories of corticolimbic regions in VP children with and without anxiety diagnosis at 13 years. METHODS: MRI data from 124 VP children were used to calculate whole brain and corticolimbic region volumes at term-equivalent age (TEA), 7 and 13 years. The presence of an anxiety disorder was assessed at 13 years using a structured clinical interview. RESULTS: VP children who met criteria for an anxiety disorder at 13 years (n = 16) displayed altered trajectories for intracranial volume (ICV, p < 0.0001), total brain volume (TBV, p = 0.029), the right amygdala (p = 0.0009) and left hippocampus (p = 0.029) compared with VP children without anxiety (n = 108), with trends in the right hippocampus (p = 0.062) and left medial orbitofrontal cortex (p = 0.079). Altered trajectories predominantly reflected slower growth in early childhood (0-7 years) for ICV (ß = -0.461, p = 0.020), TBV (ß = -0.503, p = 0.021), left (ß = -0.518, p = 0.020) and right hippocampi (ß = -0.469, p = 0.020) and left medial orbitofrontal cortex (ß = -0.761, p = 0.020) and did not persist after adjusting for TBV and social risk. CONCLUSIONS: Region- and time-specific alterations in the development of the corticolimbic system in children born VP may help to explain an increase in anxiety disorders observed in this population.

Early parenting behaviour is associated with complex attention outcomes in middle to late childhood in children born very preterm.

Attention deficits are common in children born very preterm (VP), especially for children with higher social risk. The aim of this study was to examine the association between parenting behavior and attention in children born VP, and whether this association is influenced by familial social risk. Two hundred and twenty-four children born <30 weeks' gestation and/or with a birth weight <1250 g were recruited at birth. At 2 years, social risk was calculated and parenting behaviors were observed during a parent-child interaction task, with children's attention skills assessed at 7 and 13 years using standardized assessments. Higher levels of sensitive parenting at 2 years were positively associated with divided attention at age 7 years, and higher levels of intrusive parenting were negatively associated with divided attention at 13 years. Children born VP with higher social risk were more positively influenced by sensitive parenting behavior for sustained attention at 7 years, selective attention at 13 years, and divided attention at 7 and 13 years than children born VP with lower social risk. Additionally, children born VP with higher social risk were more negatively influenced by intrusive parenting for sustained attention outcomes at 7 years than those with lower social risk. In summary, the evidence for a contribution of early parenting to attention outcomes in children born VP was stronger for more complex attention (divided attention) compared with basic attention domains. Our findings also suggest that early parenting behavior has a particular influence on children born VP from socially disadvantaged environments for attention outcomes.

Effect of a NICU to Home Physical Therapy Intervention on White Matter Trajectories, Motor Skills, and Problem-Solving Skills of Infants Born Very Preterm: A Case Series.

Infants born very preterm (VPT; ≤29 weeks of gestation) are at high risk of developmental disabilities and abnormalities in neural white matter characteristics. Early physical therapy interventions such as Supporting Play Exploration and Early Development Intervention (SPEEDI2) are associated with improvements in developmental outcomes. Six VPT infants were enrolled in a randomised clinical trial of SPEEDI2 during the transition from the neonatal intensive care unit to home over four time points. Magnetic resonance imaging scans and fixel-based analysis were performed, and fibre density (FD), fibre cross-section (FC), and fibre density and cross-section values (FDC) were computed. Changes in white matter microstructure and macrostructure were positively correlated with cognitive, motor, and motor-based problem solving over time on developmental assessments. In all infants, the greatest increase in FD, FC, and FDC occurred between Visit 1 and 2 (mean chronological age: 2.68-6.22 months), suggesting that this is a potential window of time to optimally support adaptive development. Results warrant further studies with larger groups to formally compare the impact of intervention and disparity on neurodevelopmental outcomes in infants born VPT.

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.

Brain tissue microstructural and free-water composition 13 years after very preterm birth.

There have been many studies demonstrating children born very preterm exhibit brain white matter microstructural alterations, which have been related to neurodevelopmental difficulties. These prior studies have often been based on diffusion MRI modelling and analysis techniques, which commonly focussed on white matter microstructural properties in children born very preterm. However, there have been relatively fewer studies investigating the free-water content of the white matter, and also the microstructure and free-water content of the cortical grey matter, in children born very preterm. These biophysical properties of the brain change rapidly during fetal and neonatal brain development, and therefore such properties are likely also adversely affected by very preterm birth. In this study, we investigated the relationship of very preterm birth (<30 weeks' gestation) to both white matter and cortical grey matter microstructure and free-water content in childhood using advanced diffusion MRI analyses. A total of 130 very preterm participants and 45 full-term control participants underwent diffusion MRI at age 13 years. Diffusion tissue signal fractions derived by Single-Shell 3-Tissue Constrained Spherical Deconvolution were used to investigate brain tissue microstructural and free-water composition. The tissue microstructural and free-water composition metrics were analysed using a voxel-based analysis and cortical region-of-interest analysis approach. Very preterm 13-year-olds exhibited reduced white matter microstructural density and increased free-water content across widespread regions of the white matter compared with controls. Additionally, very preterm 13-year-olds exhibited reduced microstructural density and increased free-water content in specific temporal, frontal, occipital and cingulate cortical regions. These brain tissue composition alterations were strongly associated with cerebral white matter abnormalities identified in the neonatal period, and concurrent adverse cognitive and motor outcomes in very preterm children. The findings demonstrate brain microstructural and free-water alterations up to thirteen years from neonatal brain abnormalities in very preterm children that relate to adverse neurodevelopmental outcomes.

A data driven approach to identify trajectories of prenatal alcohol consumption in an Australian population-based cohort of pregnant women.

Accurate information on dose, frequency and timing of maternal alcohol consumption is critically important when investigating fetal risks from prenatal alcohol exposure. Identification of distinct alcohol use behaviours can also assist in developing directed public health messages about possible adverse child outcomes, including Fetal Alcohol Spectrum Disorder. We aimed to determine group-based trajectories of time-specific, unit-level, alcohol consumption using data from 1458 pregnant women in the Asking Questions about Alcohol in Pregnancy (AQUA) longitudinal study in Melbourne, Australia. Six alcohol consumption trajectories were identified incorporating four timepoints across gestation. Labels were assigned based on consumption in trimester one and whether alcohol use was continued throughout pregnancy: abstained (33.8%); low discontinued (trimester one) (14.4%); moderate discontinued (11.7%); low sustained (13.0%); moderate sustained (23.5%); and high sustained (3.6%). Median weekly consumption in trimester one ranged from 3 g (low discontinued) to 184 g of absolute alcohol (high sustained). Alcohol use after pregnancy recognition decreased dramatically for all sustained drinking trajectories, indicating some awareness of risk to the unborn child. Further, specific maternal characteristics were associated with different trajectories, which may inform targeted health promotion aimed at reducing alcohol use in pregnancy.

An ode to fetal, infant, and toddler neuroimaging: Chronicling early clinical to research applications with MRI, and an introduction to an academic society connecting the field.

Fetal, infant, and toddler neuroimaging is commonly thought of as a development of modern times (last two decades). Yet, this field mobilized shortly after the discovery and implementation of MRI technology. Here, we provide a review of the parallel advancements in the fields of fetal, infant, and toddler neuroimaging, noting the shifts from clinical to research use, and the ongoing challenges in this fast-growing field. We chronicle the pioneering science of fetal, infant, and toddler neuroimaging, highlighting the early studies that set the stage for modern advances in imaging during this developmental period, and the large-scale multi-site efforts which ultimately led to the explosion of interest in the field today. Lastly, we consider the growing pains of the community and the need for an academic society that bridges expertise in developmental neuroscience, clinical science, as well as computational and biomedical engineering, to ensure special consideration of the vulnerable mother-offspring dyad (especially during pregnancy), data quality, and image processing tools that are created, rather than adapted, for the young brain.

Cohort profile: early school years follow-up of the Asking Questions about Alcohol in Pregnancy Longitudinal Study in Melbourne, Australia (AQUA at 6).

PURPOSE: The Asking Questions about Alcohol in Pregnancy (AQUA) study, established in 2011, is a prebirth cohort of 1570 mother and child pairs designed to assess the effects of low to moderate prenatal alcohol exposure and sporadic binge drinking on long-term child development. Women attending general antenatal clinics in public hospitals in Melbourne, Australia, were recruited in their first trimester, followed up three times during pregnancy and at 12 and 24 months postpartum. The current follow-up of the 6-8-year-old children aims to strengthen our understanding of the relationship between these levels of prenatal alcohol exposure and neuropsychological functioning, facial dysmorphology, brain structure and function. PARTICIPANTS: Between June 2018 and April 2021, 802 of the 1342 eligible AQUA study families completed a parent-report questionnaire (60%). Restrictions associated with COVID-19 pandemic disrupted recruitment, but early school-age neuropsychological assessments were undertaken with 696 children (52%), and 482 (36%) craniofacial images were collected. A preplanned, exposure-representative subset of 146 children completed a brain MRI. An existing biobank was extended through collection of 427 (32%) child buccal swabs. FINDINGS TO DATE: Over half (59%) of mothers consumed some alcohol during pregnancy, with one in five reporting at least one binge-drinking episode prior to pregnancy recognition. Children's craniofacial shape was examined at 12 months of age, and low to moderate prenatal alcohol exposure was associated with subtle midface changes. At 2 years of age, formal developmental assessments showed no evidence that cognitive, language or motor outcome was associated with any of exposure level. FUTURE PLANS: We will investigate the relationship between prenatal alcohol exposure and specific aspects of neurodevelopment at 6-8 years, including craniofacial shape, brain structure and function. The contribution of genetics and epigenetics to individual variation in outcomes will be examined in conjunction with national and international collaborations.

Brain White Matter Development Over the First 13 Years in Very Preterm and Typically Developing Children Based on the T 1-w/T 2-w Ratio.

BACKGROUND AND OBJECTIVES: To investigate brain regional white matter development in full-term (FT) and very preterm (VP) children at term equivalent and 7 and 13 years of age based on the ratio of T 1- and T 2-weighted MRI (T 1-w/T 2-w), including (1) whether longitudinal changes differ between birth groups or sexes, (2) associations with perinatal risk factors in VP children, and (3) relationships with neurodevelopmental outcomes at 13 years. METHODS: Prospective longitudinal cohort study of VP (born <30 weeks' gestation or <1,250 g) and FT infants born between 2001 and 2004 and followed up at term equivalent and 7 and 13 years of age, including MRI studies and neurodevelopmental assessments. T 1-w/T 2-w images were parcellated into 48 white matter regions of interest. RESULTS: Of 224 VP participants and 76 FT participants, 197 VP and 55 FT participants had useable T 1-w/T 2-w data from at least one timepoint. T 1-w/T 2-w values increased between term equivalent and 13 years of age, with little evidence that longitudinal changes varied between birth groups or sexes. VP birth, neonatal brain abnormalities, being small for gestational age, and postnatal infection were associated with reduced regional T 1-w/T 2-w values in childhood and adolescence. Increased T 1-w/T 2-w values across the white matter at 13 years were associated with better motor and working memory function for all children. Within the FT group only, larger increases in T 1-w/T 2-w values from term equivalent to 7 years were associated with poorer attention and executive function, and higher T 1-w/T 2-w values at 7 years were associated with poorer mathematics performance. DISCUSSION: VP birth and multiple known perinatal risk factors are associated with long-term reductions in the T 1-w/T 2-w ratio in white matter regions in childhood and adolescence, which may relate to alterations in microstructure and myelin content. Increased T 1-w/T 2-w ratio at 13 years appeared to be associated with better motor and working memory function and there appeared to be developmental differences between VP and FT children in the associations for attention, executive functioning, and mathematics performance.

Investigating brain structural maturation in children and adolescents born very preterm using the brain age framework.

Very preterm (VP) birth is associated with an increased risk for later neurodevelopmental and behavioural challenges. Although the neurobiological underpinnings of such challenges continue to be explored, previous studies have reported brain volume and morphology alterations in children and adolescents born VP compared with full-term (FT)-born controls. How these alterations relate to the trajectory of brain maturation, with potential implications for later brain ageing, remains unclear. In this longitudinal study, we investigate the relationship between VP birth and brain development during childhood and adolescence. We construct a normative 'brain age' model to predict age over childhood and adolescence based on measures of brain cortical and subcortical volumes and cortical morphology from structural MRI of a dataset of typically developing children aged 3-21 years (n = 768). Using this model, we examined deviations from normative brain development in a separate dataset of children and adolescents born VP (<30 weeks' gestation) at two timepoints (ages 7 and 13 years) compared with FT-born controls (120 VP and 29 FT children at age 7 years; 140 VP and 47 FT children at age 13 years). Brain age delta (brain-predicted age minus chronological age) was, on average, higher in the VP group at both timepoints compared with controls, however this difference had a small to medium effect size and was not statistically significant. Variance in brain age delta was higher in the VP group compared with controls; this difference was significant at the 13-year timepoint. Within the VP group, there was little evidence of associations between brain age delta and perinatal risk factors or cognitive and motor outcomes. Under the brain age framework, our results may suggest that children and adolescents born VP have similar brain structural developmental trajectories to term-born peers between 7 and 13 years of age.

The Structural Connectome and Internalizing and Externalizing Symptoms at 7 and 13 Years in Individuals Born Very Preterm and Full Term.

BACKGROUND: Children born very preterm (VP) are at higher risk of emotional and behavioral problems compared with full-term (FT) children. We investigated the neurobiological basis of internalizing and externalizing symptoms in individuals born VP and FT by applying a graph theory approach. METHODS: Structural and diffusion magnetic resonance imaging data were combined to generate structural connectomes and calculate measures of network integration and segregation at 7 (VP: 72; FT: 17) and 13 (VP: 125; FT: 44) years. Internalizing and externalizing symptoms were assessed at 7 and 13 years using the Strengths and Difficulties Questionnaire. Linear regression models were used to relate network measures and internalizing and externalizing symptoms concurrently at 7 and 13 years. RESULTS: Lower network integration (characteristic path length and global efficiency) was associated with higher internalizing symptoms in VP and FT children at 7 years, but not at 13 years. The association between network integration (characteristic path length) and externalizing symptoms at 7 years was weaker, but there was some evidence for differential associations between groups, with lower integration in the VP group and higher integration in the FT group associated with higher externalizing symptoms. At 13 years, there was some evidence that associations between network segregation (average clustering coefficient, transitivity, local efficiency) and externalizing symptoms differed between the VP and FT groups, with stronger positive associations in the VP group. CONCLUSIONS: This study provides insights into the neurobiological basis of emotional and behavioral problems after preterm birth, highlighting the role of the structural connectome in internalizing and externalizing symptoms in childhood and adolescence.

Predictors of long-term neurodevelopmental outcomes of children born extremely preterm.

Children born extremely preterm (<28 weeks' gestation) are at high risk of a range of adverse neurodevelopmental outcomes in later childhood compared with their peers born at term, including cognitive, motor, and behavioral difficulties. These difficulties can be associated with poorer academic achievement and health outcomes at school age. In this review, we discuss several predictors in the newborn period of early childhood neurodevelopmental outcomes including perinatal risk factors, neuroimaging findings and neurobehavioral assessments, along with social and environmental influences for children born extremely preterm. Given the complexity of predicting long-term outcomes in children born extremely preterm, we recommend multi-disciplinary teams in clinical practice to assist in determining an individual child's risk for adverse long-term outcomes and need for referral to targeted intervention, based upon their risk.

Development of brain white matter and math computation ability in children born very preterm and full-term.

Children born very preterm (VPT; <32 weeks' gestation) have alterations in brain white matter and poorer math ability than full-term (FT) peers. Diffusion-weighted magnetic resonance imaging studies suggest a link between white matter microstructure and math in VPT and FT children, although longitudinal studies using advanced modelling are lacking. In a prospective longitudinal cohort of VPT and FT children we used Fixel-Based Analysis to investigate associations between maturation of white matter fibre density (FD), fibre-bundle cross-section (FC), and combined fibre density and cross-section (FDC) and math computation ability at 7 (n = 136 VPT; n = 32 FT) and 13 (n = 130 VPT; n = 44 FT) years, as well as between change in white matter and math computation ability from 7 to 13 years (n = 103 VPT; n = 21 FT). In both VPT and FT children, higher FD, FC and FDC in visual, sensorimotor and cortico-thalamic/thalamo-cortical white matter tracts were associated with better math computation ability at 7 and 13 years. Longitudinally, accelerated maturation of the posterior body of the corpus callosum (FDC) was associated with greater math computation development. White matter-math associations were similar for VPT and FT children. In conclusion, white matter maturation is associated with math computation ability across late childhood, irrespective of birth group.