Implications of DTI in mild traumatic brain injury for detecting neurological recovery and predicting long-term behavioural outcome in paediatric and young population-a systematic review.

PURPOSE: This systematic review was done with the aim to answer these three questions: 1) Is there any change in diffusion metrics in MRI-DTI sequences after mild traumatic brain injury in paediatric and young population?, 2) Is there any correlation of these changes in diffusion metrics with severity of post concussion symptoms?, 3) Is the change in diffusion metrics predictive of neurocognitive function or neurological recovery? MATERIAL AND METHODS: Eligibility criteria- Mild TBI patients upto 22 years of age, MRI- DTI sequence done post injury, Outcome measurement with follow up at least for onemonth and articles published in English language only. Data sources- PubMed, EMBASE, CINAHL, Scopus and Cochrane RESULTS: Some studies show increased FA and some studies show decrease FA and few showed no change in white matter microstructure in mTBI patients and this depends on the duration of injury. Prediction of PCSs severity on the basis of changes in white matter microstructure showed inconsistent results. Radiological recovery in contrast to clinical recovery, is often delayed ranging from 6 months to 2-3 years. But change in diffusion metrics after mTBI is not definite predictive of neurocognitive outcomes. CONCLUSION: Large, properly designed, multicentric studies with appropriate extracranial or orthopedic control and long follow up are needed to establish the use of DTIin mTBI for predicting behavioral outcome.

Systematic review: long-term cognitive and behavioural outcomes of neonatal hypoxic-ischaemic encephalopathy in children without cerebral palsy.

AIM: To evaluate long-term cognitive and behavioural outcomes of children with neonatal hypoxic-ischaemic encephalopathy (HIE) in the absence of cerebral palsy (CP). METHODS: A systematic search was performed on five databases (EMBASE, Medline, PubMed, Web of Science, PsycInfo). Randomised controlled trials, non-randomised controlled trials, or observational studies, published between 1990 and 2017, that reported long-term (age greater than or equal to four years) cognitive and/or behavioural outcomes of neonatal HIE without CP were included. RESULTS: Seven articles met the inclusion criteria (n = 352 total participants, n = 53 treated with therapeutic hypothermia). Studies reporting cognitive outcome demonstrate impairment of general cognitive abilities in 25-63% of participants with HIE without CP. Specific cognitive difficulties were reported in two studies for attention, executive functioning, memory function and language. Results regarding behavioural outcome possibly indicate a higher risk of difficulties. CONCLUSION: A substantial proportion of children with neonatal HIE who survive without CP are at increased risk of general and/or specific cognitive impairments. Behavioural problems may be more common, but evidence is limited. Results highlight the importance of comprehensive long-term follow-up to identity difficulties and enable intervention to optimise educational achievement and behavioural adjustment.

Cognitive and behavioural outcome of children born after IVF at age 9 years.

STUDY QUESTION: Do ovarian stimulation (OS) and the in vitro laboratory procedures affect offsprings' cognitive and behavioural outcome at 9 years? SUMMARY ANSWER: OS and the in vitro laboratory procedures or the combination of both were not associated with cognitive and behavioural outcome at age 9 years. WHAT IS KNOWN ALREADY: ART is not associated with an adverse short-term developmental outcome of the offspring, but limited knowledge is available on the offspring's long-term neurodevelopmental condition. STUDY DESIGN, SIZE, DURATION: A 9-year longitudinal, assessor-blinded, prospective follow-up study of 169 out of 215 singletons (79%) born between March 2005 and December 2006 was performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Singletons born following IVF or ICSI with OS (n = 57), born after modified natural cycle IVF/ICSI (MNC-IVF/ICSI; n = 46) and born after natural conception to subfertile couples (Sub-NC; n = 66), were assessed at 9 years. This study design, with two ART groups and a subfertile reference group, allows for disentangling the effects of OS and ART procedures on developmental outcome. Cognitive outcome was evaluated with the Wechsler abbreviated scale of intelligence and the NEPSY-II. Behaviour was assessed with the child behaviour checklist (CBCL) and teacher report form (TRF). Univariable analyses and multiple linear regression models were used. MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant difference in intelligence quotient (IQ) scores between ART groups (mean IQ (95% CI): OS 114.8 (83.2-142.6); MNC 114.0 (90.2-140.8); Sub-NC 115.4 (87.9-141.2), P = 0.746). Multivariable analyses did not reveal a statistically significant association between ART group and total, verbal and performance IQ. CBCL and TRF scores did not differ significantly between ART groups (P = 0.090 and 0.507, respectively). Multivariable analyses did not demonstrate a statistically significant association between ART group and CBCL and TRF total, or internalising and externalising T-scores. No significant correlations between time to pregnancy (TTP)-a proxy for the severity of parental subfertility-and outcome measures were found (Spearman rho between -0.050 and 0.049, NS), which was confirmed with multivariable analyses. LIMITATIONS, REASONS FOR CAUTION: The attrition rate of 21% may be considered as a limitation of the study; however, after a follow-up period of 9 years, this rate is generally considered acceptable, and there were no significant differences in background characteristics between children with and without follow-up, making an attrition-related selection bias less likely. Another limitation of the study is the relatively small sample size, which could contribute to selection bias, hamper generalizability to the ART population and lead to false negative findings as a result of underpowering. An a priori power analysis on total IQ indicated that the OS-IVF/ICSI and Sub-NC groups should contain 64 children, confirming that our study including 57 and 66 children, respectively, was slightly underpowered. WIDER IMPLICATIONS OF THE FINDINGS: Our study indicated that OS and the in vitro laboratory procedures or the combination of both and TTP were not associated with cognitive and behavioural outcome at 9 years. These are reassuring results for both parents and clinicians involved in ART. STUDY FUNDING/COMPETING INTEREST(S): The study was financially supported by the University Medical Center Groningen (UMCG), two graduate schools of the UMCG (BCN and SHARE) and the Cornelia Stichting. The sponsors of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. The authors have no conflicts of interest to declare.

Diffuse traumatic axonal injury in mice induces complex behavioural alterations that are normalized by neutralization of interleukin-1ß.

Widespread traumatic axonal injury (TAI) results in brain network dysfunction, which commonly leads to persisting cognitive and behavioural impairments following traumatic brain injury (TBI). TBI induces a complex neuroinflammatory response, frequently located at sites of axonal pathology. The role of the pro-inflammatory cytokine interleukin (IL)-1ß has not been established in TAI. An IL-1ß-neutralizing or a control antibody was administered intraperitoneally at 30 min following central fluid percussion injury (cFPI), a mouse model of widespread TAI. Mice subjected to moderate cFPI (n = 41) were compared with sham-injured controls (n = 20) and untreated, naive mice (n = 9). The anti-IL-1ß antibody reached the target brain regions in adequate therapeutic concentrations (up to ~30 µg/brain tissue) at 24 h post-injury in both cFPI (n = 5) and sham-injured (n = 3) mice, with lower concentrations at 72 h post-injury (up to ~18 µg/g brain tissue in three cFPI mice). Functional outcome was analysed with the multivariate concentric square field (MCSF) test at 2 and 9 days post-injury, and the Morris water maze (MWM) at 14-21 days post-injury. Following TAI, the IL-1ß-neutralizing antibody resulted in an improved behavioural outcome, including normalized behavioural profiles in the MCSF test. The performance in the MWM probe (memory) trial was improved, although not in the learning trials. The IL-1ß-neutralizing treatment did not influence cerebral ventricle size or the number of microglia/macrophages. These findings support the hypothesis that IL-1ß is an important contributor to the processes causing complex cognitive and behavioural disturbances following TAI.

Subfertility factors rather than assisted conception factors affect cognitive and behavioural development of 4-year-old singletons.

Research on cognitive and behavioural development of children born after assisted conception is inconsistent. This prospective study aimed to explore underlying causal relationships between ovarian stimulation, in-vitro procedures, subfertility components and child cognition and behaviour. Participants were singletons born to subfertile couples after ovarian stimulation IVF (n = 63), modified natural cycle IVF (n = 53), natural conception (n = 79) and singletons born to fertile couples (reference group) (n = 98). At 4 years, cognition (Kaufmann-ABC-II; total IQ) and behaviour (Child Behavior Checklist; total problem T-score) were assessed. Causal inference search algorithms and structural equation modelling was applied to unravel causal mechanisms. Most children had typical cognitive and behavioural scores. No underlying causal effect was found between ovarian stimulation and the in-vitro procedure and outcome. Direct negative causal effects were found between severity of subfertility (time to pregnancy) and cognition and presence of subfertility and behaviour. Maternal age and maternal education acted as confounders. The study concludes that no causal effects were found between ovarian stimulation or in-vitro procedures and cognition and behaviour in childrenaged 4 years born to subfertile couples. Subfertility, especially severe subfertility, however, was associated with worse cognition and behaviour.

Parental reports of behavioural outcome among paediatric leukaemia survivors in Malaysia: a single institution experience.

OBJECTIVES: To determine the behavioural impact of chemotherapy in survivors of acute lymphoblastic leukaemia (ALL) treated with chemotherapy only and to identify treatment-related or sociodemography-related factors that might be associated with behavioural outcome. METHODS: We examined 57 survivors of childhood ALL, who were off treatment for at least 2 years and were in remission, aged 4-18 years, and 221 unrelated healthy controls. The Child Behaviour Checklist (CBCL) parent report was used either in English or in Bahasa Malaysia (the national language of Malaysia) to assess the behavioural outcome. RESULTS: Childhood ALL survivors had significantly higher scores on externalising behaviour on the CBCL parent report than did controls. Higher problem scores were found in ALL survivors with single parents on 'total problems' (P = 0.03) and subscales 'withdrawn' (P = 0.03), 'social problems' (P < 0.01) and 'delinquent behaviour' (P = 0.03) than in survivors with married parents. Significant associations were seen between a lower education level of the father and the variables representing internalising (withdrawn, anxious/depressed) and externalising (aggressive behaviour). We observed trends on higher scores in all scales in ALL survivors with single parents than in controls with single parents or with fathers with low education level, especially primary education only. CONCLUSIONS: Malaysian childhood ALL survivors had a significantly increased risk for externalising behavioural problems, and there was a trend towards increased risk of problems in many other behavioural scales. Understanding the sociocultural dimension of patients' health is important to be able to design the most appropriate remedy for problem behaviours detected in this multi-ethnic population.

Crystalising employment quality and behavioural outcomes of employees in the public service.

The goals of equitable and fair treatment in employment relationships have become a growing concern due to demographic changes and globalisation. Consequently, the quality of employment and relationships appeared to be an anachronism in competitive conditions where an organisation may need to minimise costs by reducing the headcounts. The study investigated the determinants of employment quality on employee behavioural outcomes. The study adopted a descriptive research design to establish trends related to the objectives of this study. The survey questionnaire was adopted to elicit information from the staff of the selected public (corporation) service. Out of 350 copies of the questionnaire distributed, only 230 copies were duly filled and completed. A variance-based model, specifically, SEM was adopted to establish goodness fit. Results indicate that work flexibility, learning and development, organisational culture, involvement in the determination of reward system, and work relationship significantly impact on employee behavioural outcomes. On the contrary, it was evident that the organisational policy has the least predictive value for promoting desirable outcomes. This could probably be as a result of many written rules and bureaucratic structure that exist in the public service. Differences in employees' behavioural outcomes can be linked to age (λ2 = 5.741, df = 4, P < 0.05), educational background (λ2 = 7.723, df = 4, P < 0.05) and work experience (λ2 = 9.672, df = 4, P < 0.05) while gender was not statistically significant. By implications, organisational policies should be tailored towards ensuring the quality of employment and should be targeted to facilitate commitment and positive work behaviour.

Functional outcome at school age of children born with gastroschisis.

OBJECTIVE: We aimed to determine motor, cognitive and behavioural outcomes of school aged children born with gastroschisis compared to matched controls. STUDY DESIGN: We compared outcomes of 16 children born with gastroschisis treated at the University Medical Center Groningen, the Netherlands, between 1999 and 2006 with 32 controls matched for gender, gestational age, birth weight, and corrected for small for gestational age (SGA) and parental socioeconomic status (SES). Intelligence, auditory-verbal memory, attention, response inhibition, visual perception, motor skills, visuomotor integration, problem behaviour and executive functioning were evaluated. RESULTS: Median verbal intelligence quotient and global executive functioning scores of children born with gastroschisis were poorer than of controls (95 (inter quartile range (IQR) 88-100) vs. 104 (IQR 98-113), P=0.001, and 29 (IQR 6.8-63.8) vs. 5.0 (IQR 2.8-19.8), P=0.03, respectively). Children with gastroschisis were more often classified as borderline or abnormal than controls regarding response inhibition (odds ratio (OR) 20.4; 95%-confidence interval (95%-CI); 2.4-171.5), selective visual attention (OR 40.4; 95%-CI 5.9-275.4), sustained auditory attention (OR 88.1; 95%-CI 5.8-1342.8), and fine motor skills (50% vs. 0%). Grade retention was more prevalent in gastroschisis children (OR 6.07; 95%-CI 1.42-25.9). These associations persisted after adjustment for SGA and SES. The auditory-verbal memory, visuomotor integration and behavioural problems did not significantly differ from the controls. CONCLUSIONS: Gastroschisis is associated with poorer verbal intelligence, and with an increased risk for poor performance on several aspects of attention, response inhibition and fine motor skills at school age. The follow-up of children born with gastroschisis deserves attention regarding these specific domains, to improve their functional outcomes.

Cognitive-Motivational Determinants of Residents' Civic Engagement and Health (Inequities) in the Context of Noise Action Planning: A Conceptual Model.

The Environmental Noise Directive expects residents to be actively involved in localising and selecting noise abatement interventions during the noise action planning process. Its intervention impact is meant to be homogeneous across population groups. Against the background of social heterogeneity and environmental disparities, however, the impact of noise action planning on exposure to traffic-related noise and its health effects is unlikely to follow homogenous distributions. Until now, there has been no study evaluating the impact of noise action measures on the social distribution of traffic-related noise exposure and health outcomes. We develop a conceptual (logic) model on cognitive-motivational determinants of residents' civic engagement and health (inequities) by integrating arguments from the Model on household's Vulnerability to the local Environment, the learned helplessness model in environmental psychology, the Cognitive Activation Theory of Stress, and the reserve capacity model. Specifically, we derive four hypothetical patterns of cognitive-motivational determinants yielding different levels of sustained physiological activation and expectancies of civic engagement. These patterns may help us understand why health inequities arise in the context of noise action planning and learn how to transform noise action planning into an instrument conducive to health equity. While building on existing frameworks, our conceptual model will be tested empirically in the next stage of our research process.

Behavioural and neurodevelopmental outcome of 2-year-old children after preterm premature rupture of membranes: follow-up of a randomised clinical trial comparing induction of labour and expectant management.

OBJECTIVE: We recently reported that induction of labour does not improve short term neonatal outcome in women with late preterm premature rupture of membranes (PPROM) as compared to expectant management (PPROMEXIL trial). In this study the neurodevelopmental and behavioural outcome of the children from this trial at 2 years of age was studied. STUDY DESIGN: We studied outcome of offspring of women randomised in the PPROMEXIL study. These women had >24h of ruptured membranes and were between 34 and 37 weeks of pregnancy when they were randomised to induction of labour (IoL) or expectant management (EM). Two years after delivery, the parents received the ages and stages questionnaire (ASQ), the child behaviour checklist (CBCL) and a general questionnaire. RESULTS: Follow-up data were obtained from 234 children (121 after IoL, 113 after EM, response rate 59% (44% of the original 532 randomised women)). In the IoL group 16 children (14%) had an abnormal score in ≥1 domains of the ASQ, versus 27 (26%) in the EM group (difference in percentage -11.4 (95% CI -21.9 to -0.98; p=0.033)). For the CBCL, an abnormal score was found in 13% (n=15) in the IoL group and in 15% (n=16) in the EM group (difference in percentage -2.13 (95% CI -11.2 to 6.94; p=0.645)). CONCLUSION: Although a policy of induction of labour in women with late PPROM does not improve short term neonatal outcome, it might be associated with a decrease in neurodevelopmental difficulties at the age of two years as compared to expectant management. Expectant management did not lead to a difference in behavioural problems.

Association between sensitisation and pain-related behaviours in an experimental canine model of osteoarthritis.

Evaluation of nociceptive sensitisation in canine osteoarthritis studies has been poorly reported, or even related to other clinical symptoms. In 16 dogs, peak vertical force (PVF), subjective pain assessment using 3 scales, sympathetic stress response with electrodermal activity (EDA) measurement, and behavioural changes with video analysis and telemetered motor activity were quantified at baseline (D-7), and 28 and 56 days post transection of the cranial cruciate ligament. As markers of central sensitisation, selected spinal cord biomarkers (substance P and transthyretin) were quantified at D56. Electrical withdrawal thresholds on the stifle and the tail were measured as indicative of peripheral and central quantitative sensory testing (QST) sensitisation, respectively. The effects of vehicle administration (n=8) were compared with tiludronate (2mg/kg subcutaneously, q2 week, starting at D0) administration. Generalized estimated equations tested the association between the behavioural and physiological methods and QST sensitisation, and therefore the sensitivity of the methods for detecting treatment efficacy. Compared to tiludronate, at D56, vehicle-treated dogs had increased spinal substance P (P=0.01), concomitant decreased transthyretin (P=0.02), and (compared to baseline) demonstrated peripheral and central QST sensitisation, which was not present for tiludronate. Only PVF, the spontaneous behaviour "walking with full weight-bearing," and EDA were associated with occurrence of QST sensitisation and indicated significant tiludronate analgesic efficacy after inclusion of central QST sensitisation as a predictor variable in the statistical model. This study establishes the strong interest to implement QST as a predictor of canine osteoarthritis pain symptoms explained by pain sensitisation.