Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): an international, multicentre, randomised, controlled equivalence trial

Background: In laboratory animals, exposure to most general anaesthetics leads to neurotoxicity manifested by neuronal cell death and abnormal behaviour and cognition. Some large human cohort studies have shown an association between general anaesthesia at a young age and subsequent neurodevelopmental deficits, but these studies are prone to bias. Others have found no evidence for an association. We aimed to establish whether general anaesthesia in early infancy affects neurodevelopmental outcomes. Methods: In this international, assessor-masked, equivalence, randomised, controlled trial conducted at 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand, we recruited infants of less than 60 weeks' postmenstrual age who were born at more than 26 weeks' gestation and were undergoing inguinal herniorrhaphy, without previous exposure to general anaesthesia or risk factors for neurological injury. Patients were randomly assigned (1:1) by use of a web-based randomisation service to receive either awake-regional anaesthetic or sevoflurane-based general anaesthetic. Anaesthetists were aware of group allocation, but individuals administering the neurodevelopmental assessments were not. Parents were informed of their infants group allocation upon request, but were told to mask this information from assessors. The primary outcome measure was full-scale intelligence quotient (FSIQ) on the Wechsler Preschool and Primary Scale of Intelligence, third edition (WPPSI-III), at 5 years of age. The primary analysis was done on a per-protocol basis, adjusted for gestational age at birth and country, with multiple imputation used to account for missing data. An intention-to-treat analysis was also done. A difference in means of 5 points was predefined as the clinical equivalence margin. This completed trial is registered with ANZCTR, number ACTRN12606000441516, and ClinicalTrials.gov, number NCT00756600. Findings: Between Feb 9, 2007, and Jan 31, 2013, 4023 infants were screened and 722 were randomly allocated: 363 (50%) to the awake-regional anaesthesia group and 359 (50%) to the general anaesthesia group. There were 74 protocol violations in the awake-regional anaesthesia group and two in the general anaesthesia group. Primary outcome data for the per-protocol analysis were obtained from 205 children in the awake-regional anaesthesia group and 242 in the general anaesthesia group. The median duration of general anaesthesia was 54 min (IQR 41-70). The mean FSIQ score was 99·08 (SD 18·35) in the awake-regional anaesthesia group and 98·97 (19·66) in the general anaesthesia group, with a difference in means (awake-regional anaesthesia minus general anaesthesia) of 0·23 (95% CI -2·59 to 3·06), providing strong evidence of equivalence. The results of the intention-to-treat analysis were similar to those of the per-protocol analysis. Interpretation: Slightly less than 1 h of general anaesthesia in early infancy does not alter neurodevelopmental outcome at age 5 years compared with awake-regional anaesthesia in a predominantly male study population.Mary Ellen McCann … David Costi … et al. (For the GAS Consortium

Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS)trial

Background: In laboratory animals, exposure to most general anaesthetics leads to neurotoxicity manifested by neuronal cell death and abnormal behaviour and cognition. Some large human cohort studies have shown an association between general anaesthesia at a young age and subsequent neurodevelopmental deficits, but these studies are prone to bias. Others have found no evidence for an association. We aimed to establish whether general anaesthesia in early infancy affects neurodevelopmental outcomes. Methods: In this international, assessor-masked, equivalence, randomised, controlled trial conducted at 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand, we recruited infants of less than 60 weeks' postmenstrual age who were born at more than 26 weeks

Objective Cognitive Outcomes and Subjective Emotional Sequelae in Litigating Adults with a Traumatic Brain Injury: The Impact of Performance and Symptom Validity Measures

Objective: This study examined the relative contribution of performance and symptom validity in litigating adults with traumatic brain injury (TBI), as a function of TBI severity, and examined the relationship between self-reported emotional symptoms and cognitive tests scores while controlling for validity test performance. Method: Participants underwent neuropsychological assessment between January 2012 and June 2021 in the context of compensation-seeking claims related to a TBI. All participants completed a cognitive test battery, the Personality Assessment Inventory (including symptom validity tests; SVTs), and multiple performance validity tests (PVTs). Data analyses included independent t-tests, one-way ANOVAs, correlation analyses, and hierarchical multiple regression. Results: A total of 370 participants were included. Atypical PVT and SVT performance were associated with poorer cognitive test performance and higher emotional symptom report, irrespective of TBI severity. PVTs and SVTs had an additive effect on cognitive test performance for uncomplicated mTBI, but less so for more severe TBI. The relationship between emotional symptoms and cognitive test performance diminished substantially when validity test performance was controlled, and validity test performance had a substantially larger impact than emotional symptoms on cognitive test performance. Conclusion: Validity test performance has a significant impact on the neuropsychological profiles of people with TBI, irrespective of TBI severity, and plays a significant role in the relationship between emotional symptoms and cognitive test performance. Adequate validity testing should be incorporated into every neuropsychological assessment, and associations between emotional symptoms and cognitive outcomes that do not consider validity testing should be interpreted with extreme caution

Social Cognition in Paediatric Traumatic Brain Injury: A Systematic Review and Meta-analysis

Recent evidence suggests social cognitive deficits may be among the most profound and disabling consequences of childhood traumatic brain injury (TBI); however, it is only over the last decade that this area has received increasing research attention. This study aims to systematically review all studies reporting on the effects of childhood TBI on social cognition. Meta-analytic techniques were employed to determine the magnitude of social cognitive deficits in childhood TBI. Literature searches were conducted in electronic databases (Medline/PubMed, Scopus, Cochrane, EMBASE, PsycINFO and CINAHL) to retrieve relevant articles on social cognitive outcomes of paediatric TBI published from 2007-2019. The systematic review identified fourteen eligible studies, which examined the effect of paediatric TBI on five dimensions of social cognition, including emotion recognition or perception, theory of Mind (ToM), pragmatic language, moral reasoning, and social problem solving. Of these studies, eleven articles were included in subsequent meta-analyses, which included 482 children with TBI. Meta-analysis using a random-effects model revealed non-significant differences between TBI and typically developing (TD) control groups on measures of emotion perception or recognition. In contrast, children and adolescents with TBI performed significantly worse than control groups on ToM and pragmatic language tasks, with small and medium effect sizes, respectively (Hedge's g = -0.46; -0.73). Meta-regression indicated that post-injury social cognitive deficits were not moderated by child age. While the effect of time since injury was not statistically significant, poorer social cognitive outcomes are documented soon after injury. Despite relatively intact basic social cognitive skills (i.e. emotion perception or recognition) children and adolescents with TBI are vulnerable to deficits in higher-order aspects of social cognition, including ToM and pragmatic language. These findings underscore the importance of further research, using well-validated, standardised outcome instruments, in larger paediatric TBI samples. Furthermore, longitudinal prospective studies are needed to evaluate the respective contribution of injury and non-injury factors to individual variation in outcome and recovery of social cognition after paediatric TBI

An Emotion-Focused Early Intervention for Children with Emerging Conduct Problems

This paper evaluates the real-world effectiveness of an emotion-focused, multi-systemic early intervention combining an emotion socialization parenting program with a child and school socio-emotional intervention for children with emerging conduct problems. Schools in lower socioeconomic areas of Victoria, Australia were randomized into intervention or wait-list control. Children in the first 4 years of elementary school were screened for behavior problems and those in the top 8 % of severity were invited to participate in the intervention. The study sample consisted of 204 primary caregivers and their children (Mage = 7.05, SD = 1.06; 74 % boys). Data were collected at baseline and 10 months later using parent and teacher reports and direct child assessment. Measures of parent emotion socialization, family emotion expressiveness, and children's emotion competence, social competence and behavior were administered. Results showed intervention parents but not controls became less emotionally dismissive and increased in empathy, and children showed better emotion understanding and behavior compared to control children. These outcomes lend support for an emotion-focused approach to early intervention in a real-world context for children with conduct problems