Longitudinal Preterm Cerebellar Volume: Perinatal and Neurodevelopmental Outcome Associations.

Impaired cerebellar development is an important determinant of adverse motor and cognitive outcomes in very preterm (VPT) infants. However, longitudinal MRI studies investigating cerebellar maturation from birth through childhood and associated neurodevelopmental outcomes are lacking. We aimed to compare cerebellar volume and growth from term-equivalent age (TEA) to 7 years between VPT (< 30 weeks' gestation or < 1250 g) and full-term children; and to assess the association between these measures, perinatal factors, and 7-year outcomes in VPT children, and whether these relationships varied by sex. In a prospective cohort study of 224 VPT and 46 full-term infants, cerebellar volumes were measured on MRI at TEA and 7 years. Useable data at either time-point were collected for 207 VPT and 43 full-term children. Cerebellar growth from TEA to 7 years was compared between VPT and full-term children. Associations with perinatal factors and 7-year outcomes were investigated in VPT children. VPT children had smaller TEA and 7-year volumes and reduced growth. Perinatal factors were associated with smaller cerebellar volume and growth between TEA and 7 years, namely, postnatal corticosteroids for TEA volume, and female sex, earlier birth gestation, white and deep nuclear gray matter injury for 7-year volume and growth. Smaller TEA and 7-year volumes, and reduced growth were associated with poorer 7-year IQ, language, and motor function, with differential relationships observed for male and female children. Our findings indicate that cerebellar growth from TEA to 7 years is impaired in VPT children and relates to early perinatal factors and 7-year outcomes.

Changes in verbal and visuospatial working memory from Grade 1 to Grade 3 of primary school: Population longitudinal study.

BACKGROUND: Adaptive working memory training is being implemented without an adequate understanding of developmental trajectories of working memory. We aimed to quantify from Grade 1 to Grade 3 of primary school (1) changes in verbal and visuospatial working memory and (2) whether low verbal and visuospatial working memory in Grade 1 predicts low working memory in Grade 3. METHOD: The study design includes a population-based longitudinal study of 1,802 children (66% uptake from all 2,747 Grade 1 students) at 44 randomly selected primary schools in Melbourne, Australia. Backwards Digit Recall (verbal working memory) and Mister X (visuospatial working memory) screening measures from the Automated Working Memory Assessment (M = 100; SD = 15) were used to assess Grades 1 and 3 (ages 6-7 and 8-9 years) students. Low working memory was defined as ≥1 standard deviation below the standard score mean. Descriptive statistics addressed Aim 1, and predictive parameters addressed Aim 2. RESULTS: One thousand seventy (59%) of 1802 Grade 1 participants were reassessed in Grade 3. As expected for typically developing children, group mean standard scores were similar in Grades 1 and 3 for verbal, visuospatial, and overall working memory, but group mean raw scores increased markedly. Compared to "not low" children, those classified as having low working memory in Grade 1 showed much larger increases in both standard and raw scores across verbal, visuospatial, and overall working memory. Sensitivity was very low for Grade 1 low working memory predicting Grade 3 low classifications. CONCLUSION: Although mean changes in working memory standard scores between Grades 1 and 3 were minimal, we found that individual development varied widely, with marked natural resolution by Grade 3 in children who initially had low working memory. This may render brain-training interventions ineffective in the early school year ages, particularly if (as population-based programmes usually mandate) selection occurs within a screening paradigm.

Alterations in mandibular morphology associated with glypican 1 and glypican 3 gene mutations.

OBJECTIVES: Glypican 1 (GPC1) and glypican 3 (GPC3) are bone co-regulators that act downstream in many of the signalling pathways associated with craniosynostosis. Morphometric data from GPC-knockout mice were analysed to determine whether elimination of GPC1 and GPC3 genes would alter mandibular morphology. SETTING AND SAMPLE POPULATION: The murine model included five male and five female mandibles in each of GPC1-knockout, GPC1/GPC3-knockout and wild-type (control) groups. Female GPC3-knockout mice had a very high rate of perinatal lethality, and therefore, only five males were included in this group. METHODS: The mandibular morphology of GPC1-knockout (n=10), GPC3-knockout (n=5), GPC1/GPC3-knockout (n=10) and wild-type (n=10) mice was compared by analysing five landmark-based linear dimensions: anterior and posterior lengths, as well as ascending, descending and posterior heights. Measurements were recorded on three-dimensional micro-CT reconstructions. RESULTS: GPC3-knockout mandibles were larger than wild-type mandibles for all dimensions (P<.05). Mandibular heights were more affected than lengths. A decreasing trend of mandibular dimensions across the mouse groups (GPC3-knockout>GPC1/GPC3-knockout>GPC1-knockout=wild-type) (P<.05) indicated that an increase in mandibular size was associated with increased GPC3 expression, but not GPC1. CONCLUSIONS: Alterations in GPC3 expression are likely to mediate changes to mandibular size in craniosynostosis. These findings have potential future applications in the prevention and treatment of craniosynostosis and associated craniofacial dysmorphology.

Flightless I is a key regulator of the fibroproliferative process in hypertrophic scarring and a target for a novel antiscarring therapy.

BACKGROUND: Hypertrophic scarring carries a large burden of disease, including disfigurement, pain and disability. There is currently no effective medical treatment to reduce or prevent hypertrophic scarring. Flightless I (Flii), a member of the gelsolin family of actin remodelling proteins, is an important negative regulator of wound repair. OBJECTIVES: The objective of this study was to investigate the role of Flii as a potential regulator of hypertrophic scarring. METHODS: Using human skin samples and an animal model of bleomycin-induced hypertrophic scarring in mice that overexpress or have reduced expression of Flii, we investigated its effect on dermal fibrosis and hypertrophic scarring. RESULTS: Flii expression was increased in human burns and hypertrophic scars. A similar increase in Flii was observed in hypertrophic scars formed in mice post-treatment with bleomycin. However, Flii-deficient (Flii(+/-) ) mice had reduced scarring in response to bleomycin evidenced by decreased dermal thickness, smaller cross-sectional scar areas, fewer myofibroblasts and a decreased collagen I/III ratio. In contrast, bleomycin-treated Flii-overexpressing mice (Flii(Tg/Tg) ) showed increased scar dermal thickness, larger cross-sectional scar areas, more myofibroblasts and an increased collagen I/III ratio. Injecting developing scars with a Flii neutralizing antibody led to a significant reduction in the size of the scars and a reduction in the collagen I/III ratio. CONCLUSIONS: This study identifies Flii as a profibrotic agent that contributes to excessive scar formation. Reducing its activity using neutralizing antibodies is a promising approach for reducing hypertrophic scarring.

Extremely preterm birth and adolescent mental health in a geographical cohort born in the 1990s.

BACKGROUND: Preterm birth confers risk for poor outcome, including mental health problems. Survival of extremely preterm (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g) infants increased in the 1990s but psychiatric outcomes in older adolescents born preterm since 1990 are not well documented. This study aimed to characterize mental health and personality traits in a prospective geographical cohort of adolescents born EP/ELBW in Victoria, Australia in 1991 and 1992. METHOD: At age 18 years, 215 EP/ELBW and 157 normal birthweight (>2499 g) control adolescents completed the Structured Clinical Interview for DSM-IV Disorders, Axis 1 Non-Patient version (SCID-I/NP), the Children's Interview for Psychiatric Syndromes (ChIPS) attention deficit hyperactivity disorder (ADHD) module, and questionnaires assessing recent depression and anxiety symptoms and personality traits. RESULTS: ADHD prevalence was significantly elevated in EP/ELBW adolescents compared with controls [15% v. 7%; odds ratio (OR) 2.67, 95% confidence interval (CI) 1.08-6.58]. Aside from ADHD, however, EP/ELBW and control adolescents reported very similar outcomes, with other lifetime diagnoses identified in 23% of EP/ELBW and 21% of controls. These were predominantly mood and anxiety disorders (21% EP/ELBW, 20% controls). The groups did not differ in recent depression or anxiety symptoms assessed using questionnaires, and personality traits were also similar. CONCLUSIONS: ADHD was more prevalent in EP/ELBW adolescents than controls, which is consistent with some, but not all, reports on preterm survivors born before the 1990s, and younger preterm children born in the 1990s. The high rates of anxiety and mood disorders were similar in both groups, and comparable with population-based estimates.

Genotype and clinical care correlations in craniosynostosis: findings from a cohort of 630 Australian and New Zealand patients.

Craniosynostosis is one of the most common craniofacial disorders encountered in clinical genetics practice, with an overall incidence of 1 in 2,500. Between 30% and 70% of syndromic craniosynostoses are caused by mutations in hotspots in the fibroblast growth factor receptor (FGFR) genes or in the TWIST1 gene with the difference in detection rates likely to be related to different study populations within craniofacial centers. Here we present results from molecular testing of an Australia and New Zealand cohort of 630 individuals with a diagnosis of craniosynostosis. Data were obtained by Sanger sequencing of FGFR1, FGFR2, and FGFR3 hotspot exons and the TWIST1 gene, as well as copy number detection of TWIST1. Of the 630 probands, there were 231 who had one of 80 distinct mutations (36%). Among the 80 mutations, 17 novel sequence variants were detected in three of the four genes screened. In addition to the proband cohort there were 96 individuals who underwent predictive or prenatal testing as part of family studies. Dysmorphic features consistent with the known FGFR1-3/TWIST1-associated syndromes were predictive for mutation detection. We also show a statistically significant association between splice site mutations in FGFR2 and a clinical diagnosis of Pfeiffer syndrome, more severe clinical phenotypes associated with FGFR2 exon 10 versus exon 8 mutations, and more frequent surgical procedures in the presence of a pathogenic mutation. Targeting gene hot spot areas for mutation analysis is a useful strategy to maximize the success of molecular diagnosis for individuals with craniosynostosis.

Binder syndrome.

UNLABELLED: Patients with chondrodysplasia punctata (CDP) usually present with Binder-type features, and often CDP is misdiagnosed as Binder syndrome. This study reviewed the management and outcome of patients with Binder syndrome and CDP in a multidisciplinary setting. METHODS: The notes and radiographs of the patients managed at the Australian Craniofacial Unit with a multidisciplinary setting since 1976 were reviewed, and data were collected on patient demographics, associated medical and surgical problems, subsequent management, and complications. RESULTS: Seventy-seven patients were treated over the 30-year period (5 patients were lost to follow-up); of the remaining 72 patients, 60 (83%) had Binder syndrome, and 12 (17%) were patients with CDP. Forty were males, and 32 were females, with an age range of 6 months to 47 years. Thirteen patients (18%) had a strong family history, and 65 patients (90%) have so far undergone surgical correction, and of those, 35 (54%) have completed their treatment, the longest follow-up time being 18 years. The mean number of surgical procedures was 2.4, and 18 patients (28%) had postoperative complications, which included partial necrosis of the maxilla, osteomyelitis of the mandible, facial nerve and inferior alveolar nerve neuropraxia, nasal bone graft exposure, and cellulitis. DISCUSSION: Because of the phenotypic characteristics shared by both Binder syndrome and CDP, it is most likely that Binder syndrome is not a syndrome, nor is it an entity, but most likely to be an "association." We would advocate that these patients should be managed in a multidisciplinary setting.

Longitudinal predictors of psychiatric disorders in very low birth weight adults.

The purpose of this study was to determine risk and protective factors for adult psychiatric disorders in very low birth weight (VLBW, birth weight <1,501 g) survivors. 79 of 154 (51%) VLBW subjects recruited at birth were assessed in early adulthood (24-27 years). Participants were screened for a psychiatric disorder; those elevated were invited to attend a structured clinical interview to determine a clinical diagnosis. Longitudinal variables measured from birth and at ages 2, 5, 14 and 18 years were included in analyses. Perinatal, developmental and social environmental risk factors failed to predict psychiatric disorder in adulthood in this cohort of VLBW survivors. Instead, low self-esteem at age 18 (odds ratio [OR] = 1.05, 95% confidence interval [CI] = 1, 1.11, p = 0.05) and the adult social environment (high rates of negative life event stress at the time of assessment: OR = 1.39, CI = 1.10, 1.76, p = 0.02), contributed significantly to adult psychiatric outcomes.

Prevalence of psychiatric diagnoses in preterm and full-term children, adolescents and young adults: a meta-analysis.

BACKGROUND: Preterm (PT) birth and low birth weight (LBW) are high-prevalence events that are associated with adverse outcomes in the longer term, with vulnerability increasing as maturity at birth decreases. Psychiatric symptomatology appears heightened in PT/LBW survivors, though there are some discordant findings from studies using questionnaire measures, particularly with respect to anxiety and depressive symptoms. METHOD: This article synthesises findings from research using clinical psychiatric diagnostic criteria in PT/LBW individuals aged 10-25 years compared with term-born peers. Key outcomes of interest were the rates of individuals receiving any psychiatric diagnosis and the number of diagnoses of anxiety or depressive disorders. RESULTS: A literature search for studies reporting prevalence of 'any diagnosis' yielded five studies that met inclusion criteria, with a total of 565 PT/LBW and 533 control individuals. Also, five studies were found that reported rates of anxiety/depression (692 PT/LBW and 605 control individuals). The risk of these outcomes was increased for PT/LBW individuals compared with controls [any diagnosis: odds ratio (OR) 3.66, 95% confidence interval (CI) 2.57-5.21; anxiety or depressive disorder: OR 2.86, 95% CI 1.73-4.73]. CONCLUSIONS: The studies reviewed here indicate that, in addition to monitoring and management of medical and cognitive sequelae, the psychological well-being of PT/LBW individuals should be a key part of ongoing care.

Characterisation of amyloid-induced inflammatory responses in the rat retina.

Amyloid-induced inflammation is thought to play a critical and early role in the pathophysiology of Alzheimer's disease. As such, robust models with relevant and accessible compartments that provide a means of assessing anti-inflammatory agents are essential for the development of therapeutic agents. In the present work, we have characterised the induction of inflammation in the rat retina following intravitreal administration of amyloid-beta protein (Aß). Histology and mRNA endpoints in the retina demonstrate Aß1-42-, but not Aß42-1-, induced inflammatory responses characterised by increases in markers for microglia and astrocytes (ionised calcium-binding adaptor molecule 1 (iba-1), GFAP and nestin) and increases in mRNA for inflammatory cytokines and chemokines such as IL1-ß, MIP1α and TNFα. Likewise, analysis of vitreal cytokines also revealed increases in inflammatory cytokines and chemokines, including IL1-ß, MIP1α and MCP1, induced by Aß1-42 but not Aß42-1. This profile of pro-inflammatory gene and protein expression is consistent with that observed in the Alzheimer's disease brain and suggest that this preclinical model may provide a useful relevant tool in the development of anti-inflammatory approaches directed towards Alzheimer's disease therapy.

Variability in pulmonary function following rapid altitude ascent to the Amundsen-Scott South Pole station.

The impact of acute altitude exposure on pulmonary function is variable. A large inter-individual variability in the changes in forced expiratory flows (FEFs) is reported with acute exposure to altitude, which is suggested to represent an interaction between several factors influencing bronchial tone such as changes in gas density, catecholamine stimulation, and mild interstitial edema. This study examined the association between FEF variability, acute mountain sickness (AMS) and various blood markers affecting bronchial tone (endothelin-1, vascular endothelial growth factor (VEGF), catecholamines, angiotensin II) in 102 individuals rapidly transported to the South Pole (2835 m). The mean FEF between 25 and 75% (FEF(25-75)) and blood markers were recorded at sea level and after the second night at altitude. AMS was assessed using Lake Louise questionnaires. FEF(25-75) increased by an average of 12% with changes ranging from -26 to +59% from sea level to altitude. On the second day, AMS incidence was 36% and was higher in individuals with increases in FEF(25-75) (41 vs. 22%, P = 0.05). Ascent to altitude induced an increase in endothelin-1 levels, with greater levels observed in individuals with decreased FEF(25-75). Epinephrine levels increased with ascent to altitude and the response was six times larger in individuals with decreased FEF(25-75). Greater levels of endothelin-1 in individuals with decreased FEF(25-75) suggest a response consistent with pulmonary hypertension and/or mild interstitial edema, while epinephrine may be upregulated in these individuals to clear lung fluid through stimulation of ß(2)-adrenergic receptors.

Tooth size and dental arch dimensions: a stereophotogrammetric study in Southeast Asian Malays.

OBJECTIVE: To investigate tooth size and dental arch dimensions in Malays using a stereophotogrammetric system. SETTING AND SAMPLE POPULATION: The sample consisted of 252 subjects with ages ranged from 13 to 30 years. MATERIALS AND METHODS: Images of dental casts were captured by stereophotogrammetry and selected variables were measured using a three-dimensional (3D) imaging system. Sex differences and changes associated with age were assessed, and interrelationships between different variables were explored within the study group. RESULTS: Men had significantly larger mesio-distal crown widths and dental arch dimensions than women (p < 0.05). None of the dental arch dimensions or mesio-distal crown widths showed a significant change because of age except the widths of the upper canine, lower first molar and central incisor. Significant correlations of tooth size with dental arch dimensions were found, particularly with arch lengths and perimeters. A principal component analysis showed interrelationships between the majority of tooth size variables with inter-canine width, arch length and perimeter distances. CONCLUSION: This study has established new reference data for tooth size and arch dimensions in Malays and demonstrated patterns of variation that are relevant to anthropologists interested in making comparisons within and between different populations and also to clinicians developing treatment plans for their patients. The study confirmed the accuracy of the 3D photogrammetric method for measuring dental casts.

Cognitive, behavioral and psychological functioning of children and adults with conservatively managed metopic synostosis.

Children diagnosed with metopic synostosis (MS) commonly experience poor neuropsychological outcomes, with research suggesting that children whose MS is managed conservatively (without surgery) potentially having worse outcomes than their operated peers. However, studies of children whose MS was managed conservatively are scarce. This study therefore examined the cognitive, behavioral, and psychological functioning of children/adults with conservatively managed MS (N = 38) and compares their outcomes to individually matched healthy controls (N = 38) of the same age and sex (matched-pairs design) from the general community. Age-appropriate, validated assessments measuring general cognition, verbal and visuospatial ability, attention and working memory, executive functioning, behavior, depression, anxiety, and satisfaction with appearance were utilized. Group differences were estimated using linear regression for (a) the overall sample and (b) by broad developmental stages: 2&3 yrs; ≥6-≤17. Moderate to large negative effects (g = -0.38 to -1.30) were evident before controlling for socio-economic status (SES), with the MS group performing significantly worse on 8 out of the 10 cognitive domains (general cognition, visuospatial ability, working memory, information processing, executive functioning: semantic & initial letter verbal fluency, switching, inhibition+switching). However, only initial letter verbal fluency (g = -0.99) and switching (g = -1.19) remained significant after adjusting for SES. The MS group displayed more behavioral problems, although this was not significant. Depression, anxiety, and satisfaction with appearance did not differ between the groups. Regular monitoring of cognitive functioning, particularly executive functioning, should be undertaken for those with conservatively managed MS.

Oral features in Apert syndrome: a histological investigation.

OBJECTIVES: The number of publications on the oral features in Apert syndrome is limited. The present study investigated dental tissues in Apert syndrome histologically, to determine the nature and extent of anomalies, to provide some insight into the nature of the condition, and to explain how observed anomalies may affect the dental management of individuals with Apert syndrome. SETTING AND SAMPLE POPULATION: Extracted primary and secondary teeth were collected from patients with Apert who had attended the Australian Craniofacial Unit, Adelaide, South Australia. The total study sample comprised 13 individuals, aged from 14 to 21 , with nine men and four women. MATERIAL AND METHODS: A total of 40 teeth were available for histological examination (the number belonging to each individual varied from 2 to 5 per patient). The teeth were sectioned longitudinally, and one-half of each tooth underwent decalcification. Sections were stained with H&E for routine histological examination. Ground sections were prepared from undecalcified tooth halves. RESULTS: Histological assessment of the dental hard tissues revealed an intact enamel and dentinal structure but some irregularities were noted in the region of the dentino-enamel junction (DEJ), which could affect caries progression and also make dental management more difficult. CONCLUSION: This study identified histological anomalies of the DEJ of Apert syndrome teeth. An improved appreciation of the nature and extent of dental anomalies in Apert syndrome should assist clinicians when undertaking management of affected individuals.

Management of cranial deformity following ventricular shunting.

PURPOSE: Ventricular shunt-induced craniosynostosis is a widely recognised cause of secondary craniosynostosis. We reviewed the management and long-term outcome of the cases of cranial deformity post cerebrospinal fluid shunting in our unit and compared these with previously published series. METHODS: The Australian Craniofacial Unit and Department of Neurosurgery database was searched to identify cases of ventricular shunt-induced cranial deformity and a case note review was undertaken. RESULTS: Eight cases were identified, and all were shunted within 6 months of birth. Our patients required shunting with a low pressure valve for hydrocephalus secondary to either aqueduct stenosis or intraventricular haemorrhage. The diagnosis was made following computed tomography (CT) three-dimensional surface reconstruction of the skull. Two cases of confirmed suture fusion were treated with cranial vault remodelling and programmable shunt insertion. In six cases, the sutures were not completely fused on the CT images despite a scaphocephalic head shape. These patients were managed conservatively with close monitoring. CONCLUSION: Cranial vault remodelling together with insertion of programmable shunt valve is indicated in CT confirmed cases of secondary craniosynostosis.

Cognitive, behavioral and psychological functioning in children with metopic synostosis: a meta-analysis examining the impact of surgical status.

Neurodevelopmental delays are known to occur in children with metopic synostosis, but it is presently unclear whether the cognitive, behavioral and psychological outcomes of children with metopic synostosis differ to those of their healthy peers. This meta-analysis consolidated data from 17 studies (published prior to August 2017) that examined the cognitive, behavioral and psychological outcomes of children (n = 666; aged ≤19 yrs) with metopic synostosis. Hedges'g (gw) effect sizes compared the outcomes of samples with metopic synostosis (unoperated, operated) to healthy controls or normative data and, where available, the prevalence of problems/disorders was calculated. Children with unoperated metopic synostosis performed significantly worse than their healthy peers on measures of: general cognition (gw = -.38), motor functioning, (gw = -.81), and verbal (gw = -.82) and visuospatial (gw = -.92) abilities. Children with operated metopic synostosis performed significantly worse on measures of motor functioning (gw = -.45), visuospatial skills (gw = -.32), attention (gw = -.50), executive functioning (gw = -.36), arithmetic ability (gw = -.37), and behavior (gw = -.34). Cognitive, behavioral, and psychological problems were prevalent, but variable. Overall, the cognitive, behavioral, and psychological outcomes of children with metopic synostosis are generally worse than their healthy peers, regardless of surgical status. However, research is sparse, samples small, controls are rarely recruited, and the severity of metopic synostosis often not stated. Nevertheless, the findings suggest that children with metopic synostosis are likely to experience a variety of negative outcomes and should therefore receive ongoing monitoring and support.

The prevalence of dental anomalies in an Australian population.

BACKGROUND: The aim of this study was to determine the prevalence of dental anomalies within an Australian paediatric population using panoramic radiographs. METHODS: This was a prospective review of 1050 panoramic radiographs obtained as part of a school dental screening program in suburban and rural New South Wales, Australia. RESULTS: Fifty-four (5.14%) patients had a dental anomaly present. Agenesis was noted to have occurred 69 times across 45 patients (4.28%), along with seven cases of impaction (0.6%) and three cases of supernumerary teeth (0.28%). CONCLUSIONS: Dental anomalies rarely occur in the Australian population, which possesses a wide-ranging multiethnic cohort. Despite their rarity, they can be incidentally discovered so identification and management by dental practitioners are important.

Improved neurosensory outcome at 8 years of age of extremely low birthweight children born in Victoria over three distinct eras.

AIM: To determine neurosensory outcome at 8 years of age of extremely low birthweight (ELBW) children born in the 1990s, how it varies with birth weight, and how it compares with ELBW children born in the 1980s and 1970s. METHODS: Subjects were born in the state of Victoria during 1991-92 and comprised 224 of 241 consecutive survivors with a birth weight of 500-999 g, and 223 of 262 normal birthweight (NBW) controls who had been randomly selected at birth. The comparison cohorts from earlier eras comprised 87 of 89 consecutive ELBW survivors born in 1979-80, 206 of 212 consecutive ELBW survivors born in 1985-87, and 51 of 60 randomly selected NBW survivors born in 1981-82. Survivors were assessed for neurological impairments (cerebral palsy, blindness, deafness, intellectual impairment) and disabilities at 8 years of age by paediatricians and psychologists blinded to perinatal details. RESULTS: For the 1991-92 cohorts, the rate of neurosensory disability was substantially higher in ELBW children compared with NBW controls (p<0.0001). Within the ELBW group, neurosensory disability was more prevalent in children with a birth weight of <750 g compared with a birth weight of 750-999 g (p = 0.024). Disability rates were lower in the 1991-92 ELBW cohort compared with the ELBW cohort born in 1979-80 (p = 0.046). CONCLUSIONS: Neurosensory disability rates at school age were more common in ELBW children born in the 1990s compared with NBW controls, and were significantly more common in the 500-749 g birthweight subgroup, but have improved compared with ELBW children born in earlier eras.

Neurodevelopmental sequelae of intraventricular haemorrhage at 8 years of age in a regional cohort of ELBW/very preterm infants.

BACKGROUND: Major grades of intraventricular haemorrhage (IVH) are associated with adverse neurodevelopmental sequelae in early childhood but the extent of problems in specific cognitive areas, such as executive function, and the contribution of lesser grades of IVH to neurodevelopmental problems at school age are not well described. AIMS: To determine the neuromotor, cognitive and educational outcome of extremely low birthweight (ELBW, birthweight <1000 g) or very preterm (<28 weeks) infants at 8 years of age related to the severity of IVH diagnosed in the newborn period. DESIGN: Regional cohort study. PATIENTS: Consecutive surviving children of either birthweight <1000 g or gestational age <28 weeks born in the state of Victoria in 1991 or 1992. MAIN OUTCOME MEASURES: Neurological impairments and disabilities, cognitive function and academic progress. RESULTS: Of 298 consecutive ELBW/very preterm survivors 270 (90.6%) with cranial ultrasound data were assessed at 8 years of age. Cerebral palsy, poor motor performance and major neurosensory disability were more prevalent with increasing severity of IVH. Cognitive functioning across domains was worse with increasing severity of IVH. Most of the differences were attributable to the few (n=6) survivors who had grade 4 IVH; there were few substantial differences between survivors with lesser grades of IVH. CONCLUSIONS: Neurodevelopmental dysfunction at school age in ELBW/very preterm survivors varies little with increasing severity of IVH, with the exception of grade 4 IVH.

Model of good practice tools for risk reduction and clinical governance.

Information and Communication Technologies (ICT) are expected to support Healthcare Professionals in reducing medical errors, making the most relevant decisions and finding the most appropriate procedure for each patient. In particular, Knowledge Management and Decision Support Systems provide access to high quality information and to appropriate protocols. The present paper aims at comparing the approaches used in three ongoing R&D projects in order to support risk reduction and clinical governance. This comparison will lead to the presentation of a generic model of Decision Support Tools that transform shared and documented "Good Practices" into software entities that can pro-actively advice users in their daily work or when they encounter difficult situations.