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Objectives: Retrospective harmonisation of data obtained through different instruments creates measurement error, even if the underlying concepts are assumed the same. We tested a novel method for item‐level data harmonisation of two widely used instruments that measure emotional and behavioural problems: the Child Behavior Checklist (CBCL) and the Strengths and Difficulties Questionnaire (SDQ). Methods: Item content of the CBCL and SDQ was mapped onto four dimensions: emotional problems, peer relationship problems, hyperactivity/inattention and conduct problems. A diverse test sample was drawn from four prospective longitudinal birth cohort studies in Australia and Europe who used one or both instruments. The pooled sample included 5188 data points assessing children and adolescents aged 6–13 years (N = 257–704 participants per cohort). Measurement invariance was assessed using latent variable multi‐group confirmatory factor analysis. Results: Fifteen items from the CBCL and SDQ were mapped onto four dimensions allowing for measurement invariance testing as part of a stepwise process. Partial strict invariance between CBCL and SDQ assessments was established for all four dimensions. Conclusions: The harmonised dimensions of emotional, peer relationship, hyperactivity/inattention and conduct problems are invariant across the CBCL and SDQ suggesting that these dimensions can be reliably compared with limited measurement error. [ABSTRACT FROM AUTHOR]

Objective: Dysregulation of Fibroblast Growth Factor 10 (FGF10), a member of the family of Fibroblast Growth Factor (FGF) proteins, has been implicated in craniofacial and dental anomalies, including craniosynostosis, cleft palate, and Lacrimo‐Auriculo‐Dento‐Digital Syndrome. The aim of this murine study was to assess the craniofacial and dental phenotypes associated with a heterozygous FGF10 gene (FGF10+/−) mutation at skeletal maturity. Methods: Skulls of 40 skeletally mature mice, comprising two genotypes (heterozygous FGF10+/− mutation, n = 22; wildtype, n = 18) and two sexes (male, n = 23; female, n = 17), were subjected to micro‐computed tomography. Landmark‐based linear dimensions were measured for the cranial vault, maxilla, mandible, and first molar teeth. Multivariate analysis of variance was performed to assess whether there were significant differences in the craniofacial and dental structures between genotypes and sexes. Results: The craniomaxillary skeleton and the first molar teeth were smaller in the FGF10+/− mice (P <.05), but the mandible was unaffected. Sex did not have a significant effect on these structures (P >.05). Cranial sutural defects were noted in 5/22 (22.7%) mutant versus 2/18 (11.1%) wildtype mice, and cleft palate in only one (4.5%) mutant mouse. None of the mice displayed craniosynostosis, expansive bony lesions, bifid condyles, or impacted teeth. Conclusion: The FGF10+/− mutation was associated with craniomaxillary skeletal hypoplasia that probably arose from deficient (delayed) intramembranous ossification of the sutured bones. Overall, the skeletal and dental data suggest that the FGF10 gene plays an important role in the aetiology of craniofacial dysmorphology and malocclusion. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: Systemic postnatal corticosteroids are used to treat or prevent bronchopulmonary dysplasia (BPD) in extremely preterm (EP) or extremely low birth weight (ELBW) infants but are associated with long‐term harm. We aimed to assess the relationship between cumulative postnatal corticosteroid dose and neurodevelopmental outcomes. Methods: Longitudinal cohort study of all EP/ELBW livebirths in Victoria, Australia 2016–2017. Perinatal data were collected prospectively. Neurodevelopmental assessment was performed at 2 years' corrected age. Linear and logistic regression were used to determine relationships between cumulative corticosteroid dose and neurodevelopment, adjusted for gestational age, birth weight, sex and major intraventricular haemorrhage. Results: Seventy‐six EP/ELBW infants received postnatal corticosteroids to treat or prevent BPD, 62/65 survivors were seen at 2 years. Median (IQR) cumulative postnatal corticosteroid dose was 1.36 (0.92–3.45) mg/kg dexamethasone equivalent. Higher cumulative corticosteroid dose was associated with increased odds of cerebral palsy, adjusted OR (95% CI) 1.47 (1.04, 2.07). Higher cumulative corticosteroid dose was also associated with lower cognitive and motor developmental scores, however, this weakened after adjustment for confounding variables: cognitive composite score adjusted coefficient (95% CI) −1.3 (−2.7, 0.1) and motor composite score adjusted coefficient (95% CI) −1.3 (−2.8, 0.2). Conclusion: Higher cumulative postnatal corticosteroid dose in EP/ELBW infants is associated with increased odds of cerebral palsy at 2 years' corrected age. Adequately powered studies are needed to assess the independent effects of cumulative steroid dose on neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Thus, there is great interest in interventions that improve children's working memory, such as available working memory training programmes and understanding which children benefit most. Abbreviations ADHD attention deficit/hyperactiviy disorder CI confidence interval Grit-S short grit scale IQ intellectual quotient SD standard deviation Cognitive training programmes typically require intensive practice on challenging activities and can improve children's core cognitive abilities such as working memory for up to 6 months.[[1]] Working memory, the ability to briefly hold information in mind and work with it, is important for cognitive, behavioural and academic functioning and is more likely to be reduced in children with neurodevelopmental disorders than typically developing peers. [Extracted from the article]

Aim: To describe the presence and nature of parent concerns regarding the development of their children admitted to Australian neonatal units (NNUs), comprising neonatal intensive care or special care. Methods: In a cross‐sectional survey, mothers and fathers provided information regarding concerns for their child's development. The self‐administered survey was completed by two separate cohorts; (i) parents of child graduates from Australian NNUs (n = 381); (ii) parents of infant's inpatient in two South Australian NNUs (n = 209). Data were analysed using thematic analysis and descriptive statistics. Results: Information was provided for 730 children. Developmental concern was reported for 39% of NNU graduates and 35% of inpatients. Children born very preterm (< 32 weeks' gestation) elicited greater parent concern than those born more mature (Cohort 1: 41% vs 36%; Cohort 2: 49% vs 22%), including in multiple developmental domains (Cohort 1: 17% vs 15%; Cohort 2: 28% vs 4%). Parents with inpatient infants were predominantly concerned about general development‐milestones (19.1%) and the potential impact of medical or CNS issues (13.7%). Graduate parents commonly focused on specific domains, such as their child's speech‐language (13.7%) and motor (12.9%) development. Conclusion: Neurodevelopment is a substantial source of concern for mothers and fathers during NNU admission and childhood, particularly for children born very preterm. However, in the first year of life, developmental concerns are poorly defined. This highlights the need for clinical education resources detailing infant developmental expectations and supportive strategies for parents of these high‐risk infants. [ABSTRACT FROM AUTHOR]

Background: Although outcomes for infants born extremely low birthweight (ELBW; <1000 g birthweight) have improved over time, it is important to document survival and morbidity changes following the advent of modern neonatal intensive care in the 1990s. Objective: To describe trends in survival, perinatal outcomes and neurodevelopment to 2 years' corrected age over time across six discrete geographic cohorts born ELBW between 1979 and 2017. Methods: Analysis of data from discrete population‐based prospective cohort studies of all live births free of lethal anomalies with birthweight 500–999 g in the state of Victoria, Australia, over 6 eras: 1979–80, 1985–87, 1991–92, 1997, 2005 and 2016–17. Perinatal data collected included survival, duration and type of respiratory support, neonatal morbidities and two‐year neurodevelopmental outcomes. Results: More ELBW live births were inborn (born in a maternity hospital with a neonatal intensive care unit) over time (1979–80, 70%; 2016–17, 84%), and more were offered active care (1979–80, 58%; 2016–17, 90%). Survival to 2 years rose substantially, from 25% in 1979–80 to 80% in 2016–17. In survivors, rates of any assisted ventilation rose from 75% in 1979–80 to 99% in 2016–17. Cystic periventricular leukomalacia, severe retinopathy of prematurity and blindness improved across eras. Two‐year data were available for 95% (1054/1109) of survivors. Rates of cerebral palsy, deafness and major neurodevelopmental disability changed little over time. The annual numbers with major neurodevelopmental disability increased from 12.5 in 1979–80 to 30 in 2016–17, but annual numbers free of major disability increased much more, from 31 in 1979–80 to 147 in 2016–17. Conclusions: Active care and survival rates in ELBW children have increased dramatically since 1979 without large changes in neonatal morbidities. The numbers of survivors free of major neurodevelopmental disability have increased more over time than those with major disability. [ABSTRACT FROM AUTHOR]

The cognitive functioning of children who experience intimate partner violence (IPV) has received less attention than their emotional‐behavioral outcomes. Drawing upon data from 615 (48.4% female) 10‐year‐old Australian‐born children and their mothers (9.6% of mothers born in non‐English speaking countries) participating in a community‐based longitudinal study between 2004 and 2016, this study examined the associations between IPV in infancy and cognition in middle childhood (at age 10). Results showed that IPV in the first 12 months of life was associated with lower general cognitive ability and poorer executive attention but not working memory skills. IPV in middle childhood (in the 10th year postpartum) was not associated with cognition. This study provides evidence for the long‐term impact of early life exposure to IPV on children's cognition, and points to the importance of early intervention to optimize development. [ABSTRACT FROM AUTHOR]

Aim: To investigate the strength of the independent associations of mathematics performance in children born very preterm (<32wks' gestation or <1500g birthweight) with attending postsecondary education and their current employment status in young adulthood. Method: We harmonized data from six very preterm birth cohorts from five different countries and carried out one‐stage individual participant data meta‐analyses (n=954, 52% female) using mixed effects logistic regression models. Mathematics scores at 8 to 11 years of age were z‐standardized using contemporary cohort‐specific controls. Outcomes included any postsecondary education, and employment/education status in young adulthood. All models were adjusted for year of birth, gestational age, sex, maternal education, and IQ in childhood. Results: Higher mathematics performance in childhood was independently associated with having attended any postsecondary education (odds ratio [OR] per SD increase in mathematics z‐score: 1.36 [95% confidence interval {CI}: 1.03, 1.79]) but not with current employment/education status (OR 1.14 per SD increase [95% CI: 0.87, 1.48]). Interpretation: Among populations born very preterm, childhood mathematics performance is important for adult educational attainment, but not for employment status. [ABSTRACT FROM AUTHOR]

Aim: To assess the causal effect of being born extremely preterm (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g), compared with being born at term, on neurodevelopment and social‐emotional development at 2 years' corrected age. Methods: Prospective geographical cohort study of children born EP/ELBW over 12 months in 2016 from Victoria, Australia, and term‐born controls. Children were assessed at 2 years' corrected age with the Bayley Scales of Infant and Toddler Development–3rd edition and the Infant‐Toddler Social and Emotional Assessment. Delay was defined as <−1 standard deviation relative to the mean of controls. The estimand of interest was the mean difference/odds ratio (OR) between the EP/ELBW and control groups estimated using linear/logistic regression, adjusted for multiple pregnancy and social risk. Results: A total of 205 EP/ELBW and 201 controls were assessed at 2 years. Delay/concerns were more common in the EP/ELBW group compared with controls, for cognitive (OR 3.7 [95% confidence interval 2.3, 6.0]), language (5.3 [3.1, 9.0]) and motor (3.9 [2.3, 6.3]) development, and social‐emotional competence (4.1 [1.6, 10.2]). Conclusion: Being born EP/ELBW has an adverse effect on cognitive, language and motor development, and social‐emotional competence at 2 years' corrected age. Close developmental surveillance, including social‐emotional development, is recommended. [ABSTRACT FROM AUTHOR]

Advances in perinatal medicine in high-income countries have resulted in a significant reduction in mortality for infants born very preterm (<32 weeks gestation), such that most now survive. These results are in line with those from the study by Zayegh et al.1 showing trends in extremely low birthweight outcomes over four decades in Australia were concordant with investigations in later cohorts based on gestational age. Encouragingly, however, once the severity of the very low birth weight or very preterm birth was considered, the use of birthweight or gestational age did not contribute to heterogeneity in the meta-analysis estimates of the cognitive deficit associated with very preterm birth. [Extracted from the article]

Background: Magnesium sulphate was introduced for fetal neuroprotection in Australia in 2010. The aim of this study was to determine how often antenatal magnesium sulphate is used currently and its association with cerebral palsy in children born <28 weeks' gestation. Materials and Methods: Participants comprised all survivors born <28 weeks' gestational age in the state of Victoria in 2016‐17, and earlier, in 1991‐92, 1997, 2005. Rates of cerebral palsy, diagnosed at two years for the 2016‐17 cohort, and at eight years in the earlier cohorts, were compared across eras. Within 2016‐17, the proportions of children exposed to antenatal magnesium sulphate were determined, and rates of cerebral palsy were compared between those with and without exposure to magnesium sulphate. Results: Overall, cerebral palsy was present in 6% (11/171) of survivors born in 2016‐17, compared with 12% (62/499) of survivors born in the three earlier eras (odds ratio (OR) 0.48, 95% confidence interval (CI) 0.25–0.94; P = 0.032). Data were available for 213/215 (99%) survivors born in 2016‐17, of whom 147 (69%) received magnesium sulphate. Data on cerebral palsy at two years were available for 171 (80%) survivors with magnesium data. Cerebral palsy was present in 5/125 (4%) children exposed to magnesium sulphate and in 6/46 (13%) of those not exposed (OR 0.28, 95% CI 0.08–0.96; P = 0.043). Conclusions: Antenatal magnesium sulphate is being translated into clinical practice for infants born <28 weeks' gestation, but there is room for improvement. It is associated with lower rates of cerebral palsy in survivors. [ABSTRACT FROM AUTHOR]

Background: The highly conserved Grainyhead‐like (Grhl) family of transcription factors play critical roles in the development of the neural tube and craniofacial skeleton. In particular, deletion of family member Grainyhead‐like 2 (Grhl2) leads to mid‐gestational embryonic lethality, maxillary clefting, abdominoschisis, and both cranial and caudal neural tube closure defects. These highly pleiotropic and systemic defects suggest that Grhl2 plays numerous critical developmental roles to ensure correct morphogenesis and patterning. Results: Here, using four separate Cre‐lox conditional deletion models, as well as one genetic epistasis approach (Grhl2+/−;Edn1+/− double heterozygous mice) we have investigated tissue‐specific roles of Grhl2 in embryonic development, with a particular focus on the craniofacial skeleton. We find that loss of Grhl2 in the pharyngeal epithelium (using the ShhCre driver) leads to low‐penetrance micrognathia, whereas deletion of Grhl2 within the ectoderm of the pharynx (NestinCre) leads to small, albeit significant, differences in the proximal‐distal elongation of both the maxilla and mandible. Loss of Grhl2 in endoderm (Sox17‐2aiCre) resulted in noticeable lung defects and a single instance of secondary palatal clefting, although formation of other endoderm‐derived organs such as the stomach, bladder and intestines was not affected. Lastly, deletion of Grhl2 in cells of the neural crest (Wnt1Cre) did not lead to any discernible defects in craniofacial development, and similarly, our epistasis approach did not detect any phenotypic consequences of loss of a single allele of both Grhl2 and Edn1. Conclusion: Taken together, our study identifies a pharyngeal‐epithelium intrinsic, non‐cell‐autonomous role for Grhl2 in the patterning and formation of the craniofacial skeleton, as well as an endoderm‐specific role for Grhl2 in the formation and establishment of the mammalian lung. Key Findings: Deletion of Grhl2 in the Shh‐expressing pharyngeal epithelium leads to low‐penetrance micrognathia.Deletion of Grhl2 in the Sox17‐expressing endoderm leads to subtantial lung formation and cellularity defects, and is incompatible with life.Deletion of Grhl2 in the endoderm of intestine, bladder or other tissues in which Grhl2 expression has been reported does not result in detectable developmental defects. [ABSTRACT FROM AUTHOR]

Background: Of all newborns, 1%‐2% are born very preterm (VP; <32 weeks) or with very low birthweight (VLBW; ≤1500 g). Advances in prenatal and neonatal care have substantially improved their survival, and the first generations who have benefited from these advances are now entering middle age. While most lead healthy lives, on average these adults are characterised by a number of adversities. These include cardiometabolic risk factors, airway obstruction, less physical activity, poorer visual function, lower cognitive performance, and a behavioural phenotype that includes inattention and internalising and socially withdrawn behaviour that may affect life chances and quality of life. Outcomes in later adulthood are largely unknown, and identifying trajectories of risk or resilience is essential in developing targeted interventions. Joint analyses of data and maintenance of follow‐up of cohorts entering adulthood are essential. Such analyses are ongoing within the Adults Born Preterm International Collaboration (APIC; www.apic-preterm.org). Joint analyses require data harmonisation, highlighting the importance of consistent assessment methodologies. Objective: To present an expert recommendation on Common Core Assessments to be used in follow‐up assessments of adults born preterm. Methods: Principles of Common Core Assessments were discussed at APIC meetings. Experts for each specific outcome domain wrote the first draft on assessments pertaining to that outcome. These drafts were combined and reviewed by all authors. Consensus was reached by discussion at APIC meetings. Results: We present a recommendation by APIC experts on consistent measures to be used in adult follow‐up assessments. Conclusions: The recommendation encompasses both "core" measures which we recommend to use in all assessments of adults born preterm that include the particular outcome. This will allow comparability between time and location. The recommendation also lists optional measures, focusing on current gaps in knowledge. It includes sections on study design, cardiometabolic and related biomarkers, biological samples, life style, respiratory, ophthalmic, cognitive, mental health, personality, quality of life, sociodemographics, social relationships, and reproduction. [ABSTRACT FROM AUTHOR]

Brain atlases providing standardised identification of neonatal brain regions are key in investigating neurological disorders of early childhood. Our previously developed Melbourne Children's Regional Infant Brain (M‐CRIB) and M‐CRIB 2.0 neonatal brain atlases provide standardised parcellation of 100 brain regions including cortical, subcortical, and cerebellar regions. The aim of this study was to extend M‐CRIB atlas coverage to include 54 white matter (WM) regions. Participants were 10 healthy term‐born neonates that were used to create the initial M‐CRIB atlas. WM regions were manually segmented based on T2 images and co‐registered diffusion tensor imaging‐based, direction‐encoded colour maps. Our labelled regions imitate the Johns Hopkins University neonatal atlas, with minor anatomical modifications. All segmentations were reviewed and approved by a paediatric radiologist and a neurosurgery research fellow for anatomical accuracy. The resulting neonatal WM atlas comprises 54 WM regions: 24 paired regions, and six unpaired regions comprising five corpus callosum subdivisions, and one pontine crossing tract. Detailed protocols for manual WM parcellations are provided, and the M‐CRIB‐WM atlas is presented together with the existing M‐CRIB cortical, subcortical, and cerebellar parcellations in 10 individual neonatal MRI data sets. The novel M‐CRIB‐WM atlas, along with the M‐CRIB cortical and subcortical atlases, provide neonatal whole brain MRI coverage in the first multi‐subject manually parcellated neonatal atlas compatible with atlases commonly used at older time points. The M‐CRIB‐WM atlas is publicly available, providing a valuable tool that will help facilitate neuroimaging research into neonatal brain development in both healthy and diseased states. [ABSTRACT FROM AUTHOR]

This study in children born extremely preterm (EP; <28 weeks' gestational age) or extremely low birth weight (ELBW; <1,000 g) investigated whether adaptive working memory training using Cogmed® is associated with structural and/or functional brain changes compared with a placebo program. Ninety‐one EP/ELBW children were recruited at a mean (standard deviation) age of 7.8 (0.4) years. Children were randomly allocated to Cogmed or placebo (45‐min sessions, 5 days a week over 5–7 weeks). A subset had usable magnetic resonance imaging (MRI) data pretraining and 2 weeks posttraining (structural, n = 48; diffusion, n = 43; task‐based functional, n = 18). Statistical analyses examined whether cortical morphometry, white matter microstructure and blood oxygenation level‐dependent (BOLD) signal during an n‐back working memory task changed from pretraining to posttraining in the Cogmed and placebo groups separately. Interaction analyses between time point and group were then performed. There was a significant increase in neurite density in several white matter regions from pretraining to posttraining in both the Cogmed and placebo groups. BOLD signal in the posterior cingulate and precuneus cortices during the n‐back task increased from pretraining to posttraining in the Cogmed but not placebo group. Evidence for group‐by‐time interactions for the MRI measures was weak, suggesting that brain changes generally did not differ between Cogmed and placebo groups. Overall, while some structural and functional MRI changes between the pretraining and posttraining period in EP/ELBW children were observed, there was little evidence of training‐induced neuroplasticity, with changes generally identified in both groups. Trial registration Australian New Zealand Clinical Trials Registry, anzctr.org.au; ACTRN12612000124831. [ABSTRACT FROM AUTHOR]

Aim: Brain alterations in very preterm children at risk for developmental coordination disorder were investigated.Methods: Infants born very preterm with gestation age <30 weeks or birthweight <1250 g were recruited from Royal Women's Hospital Melbourne from 2001 to 2003. Volumetric imaging was performed at term equivalent age; at seven years, volumetric imaging and diffusion tensor imaging were performed. At seven years, 53 of 162 children without cerebral palsy had scores ≤16th percentile on the Movement Assessment Battery for Children-Second Edition and were considered at risk for developmental coordination disorder.Results: At term equivalent age, smaller brain volumes were found for total brain tissue, cortical grey matter, cerebellum, caudate accumbens, pallidum and thalamus in children at risk for developmental coordination disorder (p < 0.05); similar patterns were present at seven years. There was no evidence for catch-up brain growth in at-risk children. At seven years, at-risk children displayed altered microstructural organisation in many white matter tracts (p < 0.05).Conclusion: Infants born very preterm at risk for developmental coordination disorder displayed smaller brain volumes at term equivalent age and seven years, and altered white matter microstructure at seven years, particularly in motor areas. There was no catch-up growth from infancy to seven years. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Saethre–Chotzen syndrome (SCS), associated with TWIST‐1 mutations, is characterized by premature fusion of cranial sutures. TWIST‐1 haploinsufficiency, leads to alterations in suture mesenchyme cellular gene expression patterns, resulting in aberrant osteogenesis and craniosynostosis. We analyzed the expression of the TWIST‐1 target, Tyrosine kinase receptor c‐ros‐oncogene 1 (C‐ROS‐1) in TWIST‐1 haploinsufficient calvarial cells derived from SCS patients and calvaria of Twist‐1del/+ mutant mice and found it to be highly expressed when compared to TWIST‐1 wild‐type controls. Knock‐down of C‐ROS‐1 expression in TWIST‐1 haploinsufficient calvarial cells derived from SCS patients was associated with decreased capacity for osteogenic differentiation in vitro. Furthermore, treatment of human SCS calvarial cells with the tyrosine kinase chemical inhibitor, Crizotinib, resulted in reduced C‐ROS‐1 activity and the osteogenic potential of human SCS calvarial cells with minor effects on cell viability or proliferation. Cultured human SCS calvarial cells treated with Crizotinib exhibited a dose‐dependent decrease in alkaline phosphatase activity and mineral deposition, with an associated decrease in expression levels of Runt‐related transcription factor 2 and OSTEOPONTIN, with reduced PI3K/Akt signalling in vitro. Furthermore, Crizotinib treatment resulted in reduced BMP‐2 mediated bone formation potential of whole Twist‐1del/+ mutant mouse calvaria organotypic cultures. Collectively, these results suggest that C‐ROS‐1 promotes osteogenic differentiation of TWIST‐1 haploinsufficient calvarial osteogenic progenitor cells. Furthermore, the aberrant osteogenic potential of these cells is inhibited by the reduction of C‐ROS‐1. Therefore, targeting C‐ROS‐1 with a pharmacological agent, such as Crizotinib, may serve as a novel therapeutic strategy to alleviate craniosynostosis associated with aberrant TWIST‐1 function. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Caffeine therapy for apnea of prematurity has been reported to improve brain white matter microstructure at term‐equivalent age, but its long‐term effects are unknown. This study aimed to investigate whether caffeine affects (1) brain structure at 11 years of age, and (2) brain development from term‐equivalent age to 11 years of age, compared with placebo. Methods: Preterm infants born ≤1250 g were randomly allocated to caffeine or placebo. Magnetic resonance imaging (MRI) was performed on 70 participants (33 caffeine, 37 placebo) at term‐equivalent age and 117 participants (63 caffeine, 54 placebo) at 11 years of age. Global and regional brain volumes and white matter microstructure were measured at both time points. Results: In general, there was little evidence for differences between treatment groups in brain volumes or white matter microstructure at age 11 years. There was, however, evidence that the caffeine group had a smaller corpus callosum than the placebo group. Volumetric brain development from term‐equivalent to 11 years of age was generally similar between treatment groups. However, there was evidence that caffeine was associated with slower growth of the corpus callosum, and slower decreases in axial, radial, and mean diffusivities in the white matter, particularly at the level of the centrum semiovale, over time than placebo. Interpretation: This study suggests any benefits of neonatal caffeine therapy on brain structure in preterm infants weaken over time and are not clearly detectable by MRI at age 11 years, although caffeine may have long‐term effects on corpus callosum development. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Children born very preterm (VP; <32 weeks' gestational age) are at risk for unfavorable outcomes in several cognitive domains, including spatial working memory (WM). The underlying neural basis of these cognitive impairments is poorly understood. We investigated differences in neuronal activation during spatial WM using a backward span (BS) task relative to a control (C) task in 45 VP children and 19 term-born controls aged 13 years. VP children showed significantly more activation in the bilateral superior frontal gyrus and significantly less activation in the left parahippocampal gyrus compared with controls. We further explored the distinct contributions of maintenance and manipulation processes of WM using forward span (FS)>C and BS > FS, respectively. There were no significant group differences in neuronal activation for FS > C. However, BS > FS revealed that VP children had significantly greater activation in the left middle frontal gyrus, in the left superior parietal gyrus and right cerebellar tonsil, and significantly less activation in the right precentral and postcentral gyrus and left insula compared with controls. Taken together these results suggest that VP children at 13 years of age show an atypical neuronal activation during spatial WM, specifically related to manipulation of spatial information in WM. It is unclear whether these findings reflect delayed maturation and/or recruitment of alternative neuronal networks as a result of neuroplasticity. Hum Brain Mapp 38:6172-6184, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aim: To assess the predictive validity at 4 years of the Movement Assessment Battery for Children - Second Edition (MABC-2) for motor impairment at 8 years in children born preterm. We also aimed to determine if sex, cognition, medical, or social risks were associated with motor impairment at 8 years or with a change in MABC-2 score between 4 years and 8 years.Method: Ninety-six children born at less than 30 weeks' gestation were assessed with the MABC-2 at 4 years and 8 years of age. Motor impairment was defined as less than or equal to the 5th centile. The Differential Ability Scales - Second Edition (DAS-II) was used to measure General Conceptual Ability (GCA) at 4 years, with a score <90 defined as 'below average'.Results: There was a strong association between the MABC-2 total standard scores at 4 years and 8 years (59% variance explained, regression coefficient=0.80, 95% confidence interval [CI] 0.69-0.91, p<0.001). The MABC-2 at 4 years had high sensitivity (79%) and specificity (93%) for predicting motor impairment at 8 years. Below average cognition and higher medical risk were associated with increased odds of motor impairment at 8 years (odds ratio [OR]=15.3, 95% CI 4.19-55.8, p<0.001, and OR=3.77, 95% CI 1.28-11.1, p=0.016 respectively). Sex and social risk did not appear to be associated with motor impairment at 8 years. There was little evidence that any variables were related to change in MABC-2 score between 4 years and 8 years.Interpretation: The MABC-2 at 4 years is predictive of motor functioning in middle childhood. Below average cognition and higher medical risk may be predictors of motor impairment. [ABSTRACT FROM AUTHOR]

Aim: To examine the association between newborn neurobehavioural assessments and neurodevelopmental outcomes at 2 years in infants born moderate-to-late preterm (MLPT).Method: Two-hundred and one infants born MLPT (born 32-36+6 wks' gestation) were assessed with the Hammersmith Neonatal Neurological Examination (HNNE) and NICU Network Neurobehavioral Scale (NNNS), with suboptimal performance defined as scores lower than the 10th centile. Development was assessed at 2 years corrected age with the Bayley Scales of Infant and Toddler Development 3rd Edition, with delay defined as scores less than 1 standard deviation (SD) below the mean. The relationships between neurobehaviour at term and Bayley-III cognitive, language, and motor scales at 2 years were examined using linear regression.Results: Increased odds for cognitive delay were associated with suboptimal HNNE total scores (odds ratio [OR] 2.66; 95% confidence interval [CI] 1.14-6.23, p=0.020) and suboptimal NNNS excitability (OR 3.01; 95% CI 1.33-6.82, p=0.008) and lethargy (OR 4.05; 95% CI 1.75-9.31, p=0.001) scores. Suboptimal lethargy scores on the NNNS were associated with increased odds of language (OR 5.64; 95% CI 1.33-23.85, p=0.019) and motor delay (OR: 6.86; 95% CI 1.64-28.71, p=0.08).Interpretation: Suboptimal performance on specific aspects of newborn neurobehavioural assessments is associated with neurodevelopmental delay at 2 years in children born MLPT. [ABSTRACT FROM AUTHOR]

Background Severe retinopathy of prematurity ( ROP) is associated with an increased risk for ophthalmologic morbidity, but the long-term impact in other domains is less clear. The aim of the current study was to determine whether severe ROP was related to poorer visual, cognitive, and educational outcomes in a representative sample of EP adolescents, and whether this persisted after adjusting for confounding neonatal risk factors. Method One hundred and eighty extremely preterm ( EP; <28 weeks) adolescents (17-18 years) were assessed on a range of neurodevelopmental measures, including visual processing, IQ, visual learning, visual-motor integration, and academic achievement. EP adolescents were grouped according to ROP status, (1) severe ROP (stage 3 or greater) in the worse eye; or (2) no or mild ROP and were compared on each outcome. Longitudinal data were compared at 2, 5, 8, and 17-18 years for general cognitive outcome. Results The severe ROP group performed more poorly and had more impairments than the non-severe ROP group on measures of visual processing, visual-motor integration, visual learning, IQ, and some academic achievement tests at 17-18 years of age. Group differences diminished after controlling for perinatal risk factors (severe white matter injury, post-natal corticosteroid, and surgery in the neonatal period), and only visual acuity scores remained significantly different between the groups. IQ scores remained consistently lower in the severe ROP group over time, but the magnitude reduced after adjusting for perinatal risk factors. Conclusions Extremely preterm children with severe ROP are at increased risk for ongoing visual processing difficulties and lower IQ compared with EP peers without severe ROP. While severe ROP is a predictor of long-term impairments, this association is largely mediated by other neonatal risk factors. [ABSTRACT FROM AUTHOR]

Background Very preterm birth (VPT, <32 weeks' gestation) is associated with altered white matter fractional anisotropy (FA), the biological basis of which is uncertain but may relate to changes in axon density and/or dispersion, which can be measured using Neurite Orientation Dispersion and Density Imaging (NODDI). This study aimed to compare whole brain white matter FA, axon dispersion, and axon density between VPT children and controls (born ≥37 weeks' gestation), and to investigate associations with perinatal factors and neurodevelopmental outcomes. Methods FA, neurite dispersion, and neurite density were estimated from multishell diffusion magnetic resonance images for 145 VPT and 33 control 7-year-olds. Diffusion values were compared between groups and correlated with perinatal factors (gestational age, birthweight, and neonatal brain abnormalities) and neurodevelopmental outcomes (IQ, motor, academic, and behavioral outcomes) using Tract-Based Spatial Statistics. Results Compared with controls, VPT children had lower FA and higher axon dispersion within many major white matter fiber tracts. Neonatal brain abnormalities predicted lower FA and higher axon dispersion in many major tracts in VPT children. Lower FA, higher axon dispersion, and lower axon density in various tracts correlated with poorer neurodevelopmental outcomes in VPT children. Conclusions FA and NODDI measures distinguished VPT children from controls and were associated with neonatal brain abnormalities and neurodevelopmental outcomes. This study provides a more detailed and biologically meaningful interpretation of white matter microstructure changes associated with prematurity. Hum Brain Mapp 37:3080-3102, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background Parenting influences child development, but it is unclear whether early parenting behavior can influence school-age outcomes in very preterm ( VPT) children, and/or if certain groups of VPT children may be more affected by early parenting behavior. These research questions were examined. Methods Participants were 147 children born <30 weeks' gestation or birth weight <1250 g and their primary caregiver. At term corrected age ( CA), magnetic resonance imaging ( MRI) was used to determine presence and severity of brain abnormality and medical data collected. High medical risk was defined as the presence of at least one of sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, moderate to severe white matter abnormality on MRI, or postnatal corticosteroids. At 2 years CA, parent-child interaction was assessed, and at 7 years CA, general intelligence ( IQ), language, executive function, academic skills, and social-emotional functioning were assessed. Results Higher levels of parent-child synchrony, and parent facilitation, sensitivity and positive affect at 2 years were associated with better child outcomes at 7 years, while higher levels of intrusiveness and negative affect were associated with poorer outcomes. Many of these relationships remained after controlling for early child cognitive development. Interactions between child medical risk (higher/lower) and parenting were limited to child reading, math, and executive functioning outcomes, with stronger relationships for lower medical risk children. Conclusions The contribution of early parenting to VPT children's school-age performance is significant, with stronger effects for lower medical risk children in some outcomes. These findings support the premise that parenting strategies should be included in the NICU and early interventions programs for VPT infants. [ABSTRACT FROM AUTHOR]

Very preterm (VP) survivors are at increased risk of autism spectrum disorder (ASD) compared with term-born children. This study explored whether neonatal magnetic resonance (MR) brain features differed in VP children with and without ASD at 7 years. One hundred and seventy-two VP children (<30 weeks' gestation or <1250 g birth weight) underwent structural brain MR scans at term equivalent age (TEA; 40 weeks' gestation ±2 weeks) and were assessed for ASD at 7 years of age. The presence and severity of white matter, cortical gray matter, deep nuclear gray matter, and cerebellar abnormalities were assessed, and total and regional brain volumes were measured. ASD was diagnosed using a standardized parent report diagnostic interview and confirmed via an independent assessment. Eight VP children (4.7%) were diagnosed with ASD. Children with ASD had more cystic lesions in the cortical white matter at TEA compared with those without ASD (odds ratio [OR] 8.7, 95% confidence interval [CI] 1.5, 51.3, P = 0.02). There was also some evidence for smaller cerebellar volumes in children with ASD compared with those without ASD (OR = 0.82, CI = 0.66, 1.00, P = 0.06). Overall, the results suggest that VP children with ASD have different brain structure in the neonatal period compared with those who do not have ASD. Autism Res 2016, 9: 543-552. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: Neonatal intensive care is expensive, and thus it is essential that its long-term outcomes are measured. The costs of follow-up studies for high-risk children who survive are unknown. This study aims to determine current costs for the assessment of health and development of children followed up in our research programme.Methods: Costs were determined for children involved in the research follow-up programme at the Royal Women's Hospital, Melbourne, over the 6-month period between 1st January 2012 and 30th June 2012. The time required for health professionals involved in assessments in early and later childhood was estimated, and converted into dollar costs. Costs for equipment and data management were added. Estimated costs were compared with actual costs of running the research follow-up programme.Results: A total of 134 children were assessed over the 6-month period. The estimated average cost per child assessed was $1184, much higher than was expected. The estimated cost to assess a toddler was $1149, whereas for an 11-year-old it was $1443, the difference attributable to the longer psychological and paediatric assessments. The actual average cost per child assessed was $1623. The shortfall of $439 between the actual and estimated average costs per child arose chiefly because of the need to pay staff even when participants were late or failed to attend.Conclusions: The average costs of assessing children at each age for research studies are much higher than expected. These data are useful for planning similar long-term follow-up assessments for high-risk children. [ABSTRACT FROM AUTHOR]

Objectives To determine: (1) whether corpus callosum (CC) size and microstructure at 7 years of age or their change from infancy to 7 years differed between very preterm (VP) and full-term (FT) children; (2) perinatal predictors of CC size and microstructure at 7 years; and (3) associations between CC measures at 7 years or trajectories from infancy to 7 years and neurodevelopmental outcomes. Experimental design One hundred and thirty-six VP (gestational age [GA] <30 weeks and/or birth weight <1,250 g) and 33 FT children had usable magnetic resonance images at 7 years of age, and of these, 76 VP and 16 FT infants had usable data at term equivalent age. The CC was traced and divided into six sub-regions. Fractional anisotropy, mean, axial, radial diffusivity and volume were measured from tractography. Perinatal data were collected, and neurodevelopmental tests administered at 7 years' corrected age. Principal observations VP children had smaller posterior CC regions, higher diffusivity and lower fractional anisotropy compared with FT 7-year-olds. Reduction in diffusivity over time occurred faster in VP than FT children ( P ≤ 0.002). Perinatal brain abnormality and earlier GA were associated with CC abnormalities. Microstructural abnormalities at 7 years or slower development of the CC were associated with motor dysfunction, poorer mathematics and visual perception. Conclusions This study is the first to demonstrate an accelerated trajectory of CC white matter diffusion following VP birth, associated with improved neurodevelopmental functioning. Findings suggest there is a window of opportunity for neurorestorative intervention to improve outcomes. Hum Brain Mapp 36:3733-3748, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A review of the article "Gestational age and child development at age 5 in a population-based cohort of 97,989 Australian Aboriginal and non-Aboriginal children" by M. Hanly is presented.

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. Hum Brain Mapp 36:1138-1150, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aim To compare postural control at 4 years' corrected age in very preterm children ( VPT; <30wks gestational age) with term-born (>37wks gestational age) comparison participants. Method Ninety VPT children (45 males, 45 females; mean age at assessment 4y 1mo; mean birthweight 1022g; mean gestational age 27.3wks) and 36 term comparison participants (17 males, 19 females; mean age at assessment 4y; mean birthweight 3507g; mean gestational age 39.4wks) were assessed for postural stability with a portable force plate, the Wii Balance Board. Tasks included static two-limbed standing with eyes open, eyes closed, eyes open on a foam mat, eyes closed on a foam mat, a cognitive dual task, and single leg standing on each limb. The cognitive dual task involved showing the participants a series of pictures that appeared on screen at 2-second intervals. Impaired postural control was defined as increased postural sway measured by centre of pressure path-length velocity. Functional performance was assessed during dynamic jumping and hopping tasks using the outcome measure flight time, with shorter time indicating worse performance. Results VPT children had impaired static and dynamic balance, with increased postural sway under all conditions, and reduced flight times compared with children born at term. When results were adjusted for body weight, the only group differences in postural control were in the cognitive dual task (cm/s; mean difference 0.6; 95% confidence interval [ CI] 0.02, 1.2; p=0.04) and flight times (ms; jumping; mean difference −26.0; 95% CI −47.1, −5.0; p=0.02; left leg hopping; mean difference −30.1; 95% CI −48.5, −11.8; p=0.002). Interpretation VPT children demonstrated reduced postural control at 4 years of age compared with term-born children when presented with a cognitive dual task. They also performed worse during jumping and hopping tasks. [ABSTRACT FROM AUTHOR]

The effects of prematurity on hippocampal development through early childhood are largely unknown. The aims of this study were to (1) compare the shape of the very preterm (VPT) hippocampus to that of full-term (FT) children at 7 years of age, and determine if hippocampal shape is associated with memory and learning impairment in VPT children, (2) compare change in shape and volume of the hippocampi from term-equivalent to 7 years of age between VPT and FT children, and determine if development of the hippocampi over time predicts memory and learning impairment in VPT children. T1 and T2 magnetic resonance images were acquired at both term equivalent and 7 years of age in 125 VPT and 25 FT children. Hippocampi were manually segmented and shape was characterized by boundary point distribution models at both time-points. Memory and learning outcomes were measured at 7 years of age. The VPT group demonstrated less hippocampal infolding than the FT group at 7 years. Hippocampal growth between infancy and 7 years was less in the VPT compared with the FT group, but the change in shape was similar between groups. There was little evidence that the measures of hippocampal development were related to memory and learning impairments in the VPT group. This study suggests that the developmental trajectory of the human hippocampus is altered in VPT children, but this does not predict memory and learning impairment. Further research is required to elucidate the mechanisms for memory and learning difficulties in VPT children. Hum Brain Mapp 35:4129-4139, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background The study aimed to review the presentation and long-term visual outcomes of patients with orbitotemporal neurofibromatosis. Design Retrospective case series. Participants Patients with orbitotemporal neurofibromatosis presenting from 1981 to 2009. Methods Demographic data, examination findings, causes of vision impairment and interventions performed were recorded for each patient from presentation through subsequent follow-up encounters. Visual impairment was defined as an ipsilateral Snellen acuity of <6/12. Main Outcome Measures The proportion of patients with visual impairment or enucleation, the rate of new vision loss during follow up; and causes for vision loss or enucleation. Results Thirty-seven patients (17 female) were included. Median presenting age was 15 years (range 2-45) with an average follow up of 7.4 years (range 0.5-20.3). Visual impairment occurred in 54% of patients at presentation. Causes were amblyopia (13 of 37), optic atrophy (4 of 37), previous enucleation/evisceration (2 of 37), and optic nerve glioma (1 of 37). At presentation, 76% of patients had ptosis, and 51% had strabismus. Thirty-one patients had surgery, with an average of two procedures per patient. At final follow up, 62% had visual impairment. The rate of visual decline was 2% per patient-years. Causes of visual decline were two patients with optic nerve atrophy, one with exposure keratitis and one whose cause was unknown. Five blind patients had enucleation. Conclusions The first series of orbitotemporal neurofibromatosis to focus on visual outcomes was presented. Vision loss is common, with a high prevalence of amblyopia. Close monitoring from an early age is needed to prevent visual impairment. [ABSTRACT FROM AUTHOR]

Aims The aims of the study were to investigate (1) the impact of age at brain insult on functional outcome and (2) the influence of insult and environmental factors on cognitive and behavioural outcomes. Method The study was a cross-sectional, retrospective observational study, involving 138 children (76 males, 62 females; mean age 13y 1mo, SD 1y 11mo, range 10-16y) with magnetic resonance imaging ( MRI) evidence of focal brain insult sustained from the first trimester of pregnancy to adolescence. Children underwent MRI and intellectual, executive, behavioural, and social evaluation. Outcome predictors were insult (lesion location, laterality, and extent, history of seizures, age at insult) and environmental (social risk and family function) factors. Results Focal insult before the age of 3 years was associated with poorer outcomes than insult after the age of 3 years across all domains. For IQ outcomes, insult characteristics and seizures were highly predictive. For executive and behavioural domains, family function and social risk had the greatest impact. Earlier age at insult predicted poorer social competence. Interpretation Focal brain insult before age 3 years has devastating consequences for children's development. Findings suggest that greater emphasis should be placed on providing early intervention for children who sustain early focal brain insults. [ABSTRACT FROM AUTHOR]

Aims The American Academy of Pediatrics recommends that test scores should be corrected for prematurity up to 3 years of age, but this practice varies greatly in both clinical and research settings. The aim of this study was to contrast the effects of using chronological age and those of using corrected age on measures of cognitive outcome across childhood. Methods A theoretical model was constructed using norms from the Bayley Scales of Infant and Toddler Development, Third Edition; the Wechsler Preschool and Primary Scale of Intelligence, Third Edition Australian; and the Wechsler Intelligence Scales for Children, Fourth Edition Australian. Baseline scores representing different levels of functioning (70, below average; 85, borderline; and 100, average) were recalculated using the normative data for ages 6 months to 16 years to account for 1, 2, 3 and 4 months of prematurity. The model created depicted the difference in standardised scores between chronological and corrected age. Results Compared with scores corrected for prematurity, the absolute reduction in scores using chronological age was greater for increasing degree of prematurity, younger ages at assessment and higher baseline scores and was substantial even beyond 3 years of age. However, the pattern was erratic, with considerable fluctuation evident across different ages and baseline scores. Conclusions Chronological age results in a lowering of scores at all ages for preterm-born subjects that is greater in the first few years and in those born at earlier gestational ages. Whether or not to correct for prematurity depends upon the context of the assessment. [ABSTRACT FROM AUTHOR]

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

AIM: To assess the predictive validity of the Bayley Scales of Infant and Toddler Development - Third Edition (Bayley-III) for later motor outcome. METHOD: Ninety-six infants (49 males, 47 females) born at less than 30 weeks' gestation admitted to two tertiary hospitals in Melbourne, Australia, were assessed with the Bayley-III Motor Scale at 2 years' corrected age and were classified as suspect or definite motor impairment if they scored less than -1 or -2 standard deviations respectively, relative to the test mean. At 4 years' corrected age, children completed Movement Assessment Battery for Children - Second Edition (MABC-2); for the total motor score, cut-offs of not more than the 15th were used to classify motor development and cut-offs of not more than the 15th centile were classified as having a significant movement difficulty. RESULTS: Of the 96 children assessed at both ages, at 2 years 9% had suspect and 4% had definite motor impairment; however, by 4 years, rates had increased to 22% and 19% respectively. The specificity of the Bayley-III for motor impairments for later motor outcome was excellent (ranging from 94 to 100% for cerebral palsy [CP] and 97 to 100% for motor impairment), although the sensitivity was low (ranging from 67 to 83% for CP and 18 to 37% for motor impairment); many children with later impairment were not identified by the Bayley-III. INTERPRETATION: The Bayley-III Motor Scale at 2 years underestimates later rates of motor impairment, particularly in the absence of CP at 4 years on the MABC-2 total motor score in children born at less than 30 weeks' gestational age. [ABSTRACT FROM AUTHOR]

Aim The aim of the study was to evaluate the psychometric properties and clinical use of assessments of sensory processing function, within the first 2 years of life, and to identify which assessment is the most appropriate and precise in measuring the construct of sensory processing. Method The literature was comprehensively searched, and assessments used to measure sensory processing in infancy were systematically selected and reviewed for clinical use, reliability, validity, and responsiveness. Results Thirty-four assessments were identified; three met the predefined inclusion criteria. All discriminative assessments, the Sensory Rating Scale, and Infant/Toddler Sensory Profile are parent-reported questionnaires and can be administered from birth up to 3 years of age. The Test of Sensory Function in Infants is a performance-based assessment and is suitable for infants aged 4 to 18 months. Studies evaluating the psychometric properties of these three assessments differed in the properties addressed and reported poor to adequate reliability. Interpretation Selecting the most appropriate and precise assessment to measure sensory processing function in infancy will depend on the specific components of sensory processing that need to be evaluated, infant age, and what other sources of information are available about the infant's development. [ABSTRACT FROM AUTHOR]

Aim Children born very preterm are at risk for impaired motor performance ranging from cerebral palsy (CP) to milder abnormalities, such as developmental coordination disorder. White matter abnormalities (WMA) at term have been associated with CP in very preterm children; however, little is known about the impact of WMA on the range of motor impairments. The aim of this study was to assess whether WMA were predictive of all levels of motor impairments in very preterm children. Method Two hundred and twenty-seven very preterm infants (<30wks gestational age or birthweight <1250g) had brain magnetic resonance imaging at term-equivalent age to assess for WMA, which were categorized as nil, mild, or moderate to severe. At 5 years of age children were classified as having a moderate to severe motor impairment if they were below the 5th centile or mild to severe motor impairment if their score placed them no higher than the 15th centile on the Movement Assessment Battery for Children (MABC). WMA (nil vs mild and nil vs moderate-severe) were explored as predictors of motor impairment using logistic regression. Analyses were repeated adjusting for the effects of other perinatal variables and excluding children with CP. Results Of the 193 very preterm children (97 males, 96 females) assessed with the MABC, 53 (27%) were classified as having a moderate to severe motor impairment and 96 (50%) a mild to severe motor impairment. WMA were predictive of motor impairment in very preterm children, with mild versus no WMA increasing the odds of moderate to severe motor impairment by over fivefold (odds ratio [OR] 5.6; 95% confidence interval [CI] 1.9-16.1; p=0.002) and mild to severe impairment by twofold (OR 2.2; 95% CI 1.1-4.2; p=0.02). Compared with no WMA, moderate to severe WMA increased the odds for moderate to severe impairment 19-fold (OR 19.4; 95% CI 5.6-66.7; p<0.001) and for mild to severe motor impairment ninefold (OR 9.4; 95% CI 3.2-28.1; p<0.001). Results remained similar after controlling for several potential confounders and after excluding 14 children who had CP at age 2 years. Interpretation WMA predict motor impairment at 5 years, with rates of impairment increasing with more severe WMA. Very preterm children with any WMA at term require follow-up throughout childhood. [ABSTRACT FROM AUTHOR]

Aim Extremely preterm and extremely low-birthweight (EP/ELBW) children (<28 completed weeks' gestation; birthweight <1000g) have a high risk of long-term adverse outcomes. Clinical developmental surveillance is difficult to achieve for all of these children. Our aim was to study the ability of two parent-completed questionnaires to differentiate health status of EP/ELBW children from that of a comparison group of children born at term, and to screen EP/ELBW children for disability compared with the ability of a multidisciplinary clinical assessment. Method A geographic cohort of 189 EP/ELBW children (100 males, 89 females) and a comparison group of 173 term children (92 males, 81 females) born in 1997 were assessed at the age of 8 years using parent questionnaires (the Child Health Questionnaire [CHQ] and the Health Utilities Index Mark 2 [HUI2]) and a multidisciplinary clinical assessment. The questionnaires and clinical assessment were compared with respect to their ability to differentiate between the health status of EP/ELBW children and children born at term and also to identify children with a disability. Results The HUI2 was better than the CHQ at differentiating the health status of EP/ELBW and comparison children. Moderate and severe disability status were identified by the HUI2 with sensitivity ranging from 86 to 97%, specificity from 60 to 64%, positive predictive values from 34 to 39%, and negative predictive values from 95 to 99%. Interpretation The HUI2 had suitable sensitivity and specificity to be used as a developmental screening tool for EP/ELBW children, but the CHQ did not. Given its low positive predictive values, however, the HUI2 should be viewed with caution as a final outcome measure for intervention trials, and would be better used to identify at-risk children who need a definitive clinical assessment. [ABSTRACT FROM AUTHOR]

Abstract: We have studied scalding-type burn injury-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the spinal dorsal horn, which is a recognised marker for spinal nociceptive processing. At 5min after severe scalding injury to mouse hind-paw, a substantial number of phosphorylated ERK1/2 (pERK1/2) immunopositive neurons were found in the ipsilateral dorsal horn. At 1h post-injury, the number of pERK1/2-labelled neurons remained substantially the same. However, at 3h post-injury, a further increase in the number of labelled neurons was found on the ipsilateral side, while a remarkable increase in the number of labelled neurons on the contralateral side resulted in there being no significant difference between the extent of the labelling on both sides. By 6h post-injury, the number of labelled neurons was reduced on both sides without there being significant difference between the two sides. A similar pattern of severe scalding injury-induced activation of ERK1/2 in spinal dorsal horn neurons over the same time-course was found in mice which lacked the transient receptor potential type 1 receptor (TRPV1) except that the extent to which ERK1/2 was activated in the ipsilateral dorsal horn at 5min post-injury was significantly greater in wild-type animals when compared to TRPV1 null animals. This difference in activation of ERK1/2 in spinal dorsal horn neurons was abolished within 1h after injury, demonstrating that TRPV1 is not essential for the maintenance of ongoing spinal nociceptive processing in inflammatory pain conditions in mouse resulting from at least certain types of severe burn injury. [Copyright &y& Elsevier]

The aim of the study was to examine the prevalence of developmental coordination disorder (DCD) at the age of 8 years in a geographic cohort of extremely preterm or extremely-low-birthweight (EP/ELBW) children and a term-born comparison group, as well as associated academic outcomes, parents' perceptions of motor performance, and changes in prevalence during the 1990s. Moderate DCD was defined as a score below the 5th centile on the Movement Assessment Battery for Children in children without cerebral palsy or intellectual impairment. DCD rates were compared in a group of 132 8-year-old children born in 1997 at 22 to 27 weeks' gestation or birthweight of less than 1000g (49% male, 51% female) and a comparison group of 154 term-born children (55% male, 45% female). The Wechsler Intelligence Scale for Children - 4th edition and the Wide Range Achievement Test - 3rd edition were used to measure academic and cognitive outcomes. Parental perceptions of motor performance were measured using the physical function scale of the Child Health Questionnaire, parent-report form (CHQ PF50). The results for children with and without DCD were then compared. To assess changes in prevalence throughout the 1990s, DCD rates were compared with those found in children from the same region born in 1991 to 92. The mean number of completed weeks of gestation in the EP/ELBW children and in the comparison group of term-born children for whom data were available for analysis was 26.5 (SD 1.9) and 39.2 (SD 1.1) respectively, and the mean birthweight was 830g (SD 163) and 3511g (SD 462) respectively. The prevalence of DCD was 16% in the EP/ELBW group and 5% in the comparison group (odds ratio 3.45; 95% confidence interval [CI] 1.47-8.09%). Academic outcomes for reading, spelling, and arithmetic were poorer among children with DCD than among those without DCD (mean difference [95% CI] 10.2 [0.9-19.7; p=0.03], 8.9 [2.2-15.5; p=0.01], and 7.9 [1.4-14.5; p=0.02] respectively). Parental perceptions were poorly predictive of DCD. EP/ELBW children have higher rates of DCD and experience more academic difficulties than term-born children. As parental perceptions are not a reliable screen, clinical assessments of motor skills in this vulnerable population are important. [ABSTRACT FROM AUTHOR]

Objective: Caffeine improves neurological outcome in very preterm infants, but the mechanisms responsible for this neurological benefit are unknown. The objective of this study was to assess whether caffeine influenced brain macro- or microstructural development in preterm infants. Methods: Seventy preterm infants <1,251 g birthweight randomly allocated to either caffeine (n = 33) or placebo (n = 37) underwent brain magnetic resonance imaging (MRI) at term-equivalent age; white and gray matter abnormalities were qualitatively scored, global and regional brain volumes were measured, and white matter microstructure was evaluated using diffusion-weighted imaging. Results: There were no significant differences between the groups in the extent of white matter or gray matter abnormality, or in global or regional brain volumes. In contrast, although only available in 28 children, caffeine exposure was associated with reductions in the apparent diffusion coefficient, and radial and axial diffusivity with the greatest impact in the superior brain regions. The alterations in diffusion measures were not mediated by lowering the rate of lung injury, known as bronchopulmonary dysplasia. Interpretation: These diffusion changes are consistent with improved white matter microstructural development in preterm infants who received caffeine. ANN NEUROL 2010;68:734-742 [ABSTRACT FROM AUTHOR]

Aim Motor skill impairment is a common negative outcome in children born preterm who do not develop cerebral palsy (CP). This study aimed to conduct a systematic review of current data to provide an accurate estimate of the prevalence of non-CP motor impairment in preterm children at school age. Method We searched the Medline, PubMed, and PsycInfo databases and relevant journals to identify all studies published post-1990 that reported the prevalence of motor impairment in school-aged children born preterm (<37wks’ gestation) using standardised motor assessment batteries. We applied a range of exclusionary criteria, with 11 studies included in the final analyses. We identified two levels of motor impairment commonly reported – mild–moderate and moderate – and conducted a random effects meta-analysis to produce a prevalence estimate for each. Results The pooled estimate for mild–moderate impairment in preterm children was 40.5/100. and for moderate motor impairment the estimate was 19.0/100. There was also a trend for lower motor impairment levels in samples born before 1990 compared with those born after 1990. Interpretation Children born preterm are at increased risk of motor impairment, with prevalence three to four times greater than in the general population. This highlights the need for improved surveillance and intervention strategies in this group of children. [ABSTRACT FROM AUTHOR]

Children with very low birth weight (VLBW, <1500 g) or very preterm birth (VPTB, <32 weeks gestational age or GA) have more mathematics disabilities or deficiencies (MD) and higher rates of mathematics learning disabilities (MLD) than normal birth weight term-born children (NBW, >2500 g and >36 weeks GA). MD are found even in children without global disorders in cognition or neurosensory status and when IQ is controlled, and they are associated with other learning problems and weaknesses in perceptual motor abilities and executive function. Factors related to poorer mathematics outcomes include lower birth weight and GA, neonatal complications, and possible abnormalities in brain structure. While little is known about the nature of MD in these children, studies of MLD in other neurodevelopmental disorders and in children with learning disabilities provide useful models for further investigation. Further investigation of the neuropsychological and neuropathological correlates of distinct types of mathematics difficulties is also needed. Studies along these lines will yield information about the unique features of MD in children with VLBW/VPTB and about the nature and origins of poor mathematics achievement more generally. © 2009 Wiley-Liss, Inc. Dev Disabil Res Rev 2009;15:52–59. [ABSTRACT FROM AUTHOR]

Osteogenic supplements are a requirement for osteoblastic cell differentiation during in vitro culture of human calvarial suture-derived cell populations. We investigated the ability of ascorbic acid and β-glycerophosphate with and without the addition of dexamethasone to stimulate in vivo-like osteoblastic differentiation. Cells were isolated from unfused and prematurely fused suture tissue from patients with syndromic and non-syndromic craniosynostosis and cultured in each osteogenic medium for varying lengths of time. The effect of media supplementation was investigated with respect to the ability of cells to form mineralised bone nodules and the expression of five osteodifferentiation marker genes (COL1A1, ALP, BSP, OC and RUNX2), and five genes that are differentially expressed during human premature suture fusion (GPC3, RBP4, C1QTNF3, WIF1 and FGF2). Cells from unfused sutures responded more slowly to osteogenic media but formed comparable bone nodules to fused suture-derived cells after 16 days of culture in either osteogenic media. However, gene expression differed between unfused and fused suture-derived cells, as did expression in each osteogenic medium. When compared to expression in the explant tissue of origin, neither medium induced a level or profile of gene expression similar to that seen in vivo. Overall, our results demonstrate that cells from the same suture that are isolated during different stages of morphogenesis in vivo, despite being de-differentiated to a similar level in vitro, respond uniquely and differently to each osteogenic medium. Further, we suggest that neither cell culture medium recapitulates differentiation via activation of the same genetic cascades as occurs in vivo. J. Cell. Physiol. 218: 183–191, 2009. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]