Acetylcholinesterase inhibitors for autistic spectrum disorders.

BACKGROUND: Autism spectrum disorder (autism) is a neurodevelopmental condition characterised by impairments in social communication and interaction, plus restricted, repetitive patterns of behaviour and interests. Whilst some people embrace autism as part of their identity, others struggle with their difficulties, and some seek treatment. There are no current interventions that result in complete reduction of autism features. Acetylcholine is a neurotransmitter for the cholinergic system and has a role in attention, novelty seeking, and memory. Low levels of acetylcholine have been investigated as a potential contributor to autism symptomatology. Donepezil, galantamine, and rivastigmine (commonly referred to as acetylcholinesterase inhibitors) all inhibit acetylcholinesterase, and have slightly different modes of action and biological availability, so their effectiveness and side-effect profiles may vary. The effect of various acetylcholinesterase inhibitor on core autism features across the lifespan, and possible adverse effects, have not been thoroughly investigated. OBJECTIVES: To evaluate the efficacy and harms of acetylcholinesterase inhibitors for people with the core features (social interaction, communication, and restrictive and repetitive behaviours) of autism. To assess the effects of acetylcholinesterase inhibitors on non-core features of autism. SEARCH METHODS: In November 2022, we searched CENTRAL, MEDLINE, Embase, eight other databases, and two trials registers. We also searched the reference lists of included studies and relevant reviews, and contacted authors of relevant studies. SELECTION CRITERIA: Randomised controlled trials (RCTs), comparing acetylcholinesterase inhibitors (e.g. galantamine, donepezil, or rivastigmine) of varying doses, delivered orally or via transdermal patch, either as monotherapy or adjunct therapy, with placebo. People of any age, with a clinical diagnosis of autism were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were core features of autism and adverse effects. Secondary outcomes were language, irritability, hyperactivity, and general health and function. We used GRADE to assess certainty of evidence. MAIN RESULTS: We included two RCTs (74 participants). One study was conducted in Iran, the second in the USA, although exact location in the USA is unclear. Galantamine plus risperidone versus placebo plus risperidone One study compared the effects of galantamine plus risperidone to placebo plus risperidone (40 participants, aged 4 years to 12 years). Primary and secondary outcomes of interest were measured postintervention, using subscales of the Aberrant Behavior Checklist (score 0 to 3; higher scores = greater impairment). Very low-certainty evidence showed there was little to no difference between the two groups postintervention for social communication (mean difference (MD) -2.75, 95% confidence interval (CI) -5.88 to 0.38), and restricted and repetitive behaviour (MD -0.55, 95% CI -3.47 to 2.37). Overall autism features were not assessed. Adverse events may be higher in the galantamine plus risperidone group (75%) compared with the placebo plus risperidone group (35%): odds ratio 5.57, 95% CI 1.42 to 21.86, low-certainty evidence. No serious adverse events were reported. Low-certainty evidence showed a small difference in irritability (MD -3.50, 95% CI -6.39 to -0.61), with the galantamine plus risperidone group showing a greater decline on the irritability subscale than the placebo group postintervention. There was no evidence of a difference between the groups in hyperactivity postintervention (MD -5.20, 95% CI -10.51 to 0.11). General health and function were not assessed. Donepezil versus placebo One study compared donepezil to placebo (34 participants aged 8 years to 17 years). Primary outcomes of interest were measured postintervention, using subscales of the Modified Version of The Real Life Rating Scale (scored 0 to 3; higher scores = greater impairment). Very low-certainty evidence showed no evidence of group differences immediately postintervention in overall autism features (MD 0.07, 95% CI -0.19 to 0.33), or in the autism symptom domains of social communication (MD -0.02, 95% CI -0.34 to 0.30), and restricted and repetitive behaviours (MD 0.04, 95% CI -0.27 to 0.35). Significant adverse events leading to study withdrawal in at least one participant was implied in the data analysis section, but not explicitly reported. The evidence is very uncertain about the effect of donepezil, compared to placebo, on the secondary outcomes of interest, including irritability (MD 1.08, 95% CI -0.41 to 2.57), hyperactivity (MD 2.60, 95% CI 0.50 to 4.70), and general health and function (MD 0.03, 95% CI -0.48 to 0.54) postintervention. Across all analyses within this comparison, we judged the evidence to be very low-certainty due to high risk of bias, and very serious imprecision (results based on one small study with wide confidence intervals). The study narratively reported adverse events for the study as a whole, rather than by treatment group. AUTHORS' CONCLUSIONS: Evidence about the effectiveness of acetylcholinesterase inhibitors as a medication to improve outcomes for autistic adults is lacking, and for autistic children is very uncertain. There is a need for more evidence of improvement in outcomes of relevance to clinical care, autistic people, and their families. There are a number of ongoing studies involving acetylcholinesterase inhibitors, and future updates of this review may add to the current evidence.

The Feedback Session of an Autism Assessment: A Scoping Review of Clinical Practice Guideline Recommendations.

This review aimed to assess the quality and content of recommendations for delivering an autism diagnosis, published internationally within clinical practice guidelines. Seventeen relevant guidelines were identified. When methodological information was provided, recommendations for feedback were predominantly formed through consensus. Recommendations consistently included who should attend feedback, the timing and mode of delivery, the clinician's manner, and what should be discussed and/or included in an accompanying report. Specific recommendations were not consistent however, and a number of gaps were identified, such as the inclusion of educators and educational specific recommendations. Although individual variation is necessary for autism diagnosis disclosure, agreement on minimum standards of practice is warranted. Further investigation is required to establish best practice.

Repetitive and restricted behaviours and anxiety in autism spectrum disorder: protocol for a systematic review and meta-analysis.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by persistent deficits in social functioning and the presence of restricted and repetitive behaviours (RRBs). RRBs refer to four subtypes of behaviour including repetitive movements, speech, or use of objects; insistence on sameness; restricted interests; and sensory processing abnormalities. Many individuals with ASD also experience anxiety, which compounds ASD-related difficulties and inhibits daily functioning. RRBs have been found to be positively associated with anxiety; however, our understanding of the interplay between RRB subtypes and anxiety remains unclear. Thus, the current review aims to clarify the association between RRBs and anxiety by conducting a systematic review and meta-analysis. METHODS: To identify relevant studies, we will search five databases: CINAHL Plus, Cochrane Central Register of Controlled Trials, Ovid MEDLINE, PsycINFO, and Scopus. Articles included in the review will have their titles, abstracts, and full texts reviewed by two independent authors and their methodological quality assessed via the modified Newcastle-Ottawa Scale. Random-effects meta-analyses will then be conducted to calculate the pooled association between RRB subtypes and anxiety. Sensitivity analyses will also be conducted to assess the potential impact of bias, missing data, outliers, and methodological differences on this relationship. Additionally, this review will collate the factors which may influence the anxiety-RRB relationship to help identify who is most vulnerable to developing anxiety. DISCUSSION: This will be the first review to examine the association between the four subtypes of RRBs and anxiety in individuals with ASD. Understanding this relationship, and the factors associated with this, may help clinicians understand the different underpinnings and presentations of anxiety within this population with potential implications for assessment and treatment. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020185434.

The Monash Autism-ADHD genetics and neurodevelopment (MAGNET) project design and methodologies: a dimensional approach to understanding neurobiological and genetic aetiology.

BACKGROUND: ASD and ADHD are prevalent neurodevelopmental disorders that frequently co-occur and have strong evidence for a degree of shared genetic aetiology. Behavioural and neurocognitive heterogeneity in ASD and ADHD has hampered attempts to map the underlying genetics and neurobiology, predict intervention response, and improve diagnostic accuracy. Moving away from categorical conceptualisations of psychopathology to a dimensional approach is anticipated to facilitate discovery of data-driven clusters and enhance our understanding of the neurobiological and genetic aetiology of these conditions. The Monash Autism-ADHD genetics and neurodevelopment (MAGNET) project is one of the first large-scale, family-based studies to take a truly transdiagnostic approach to ASD and ADHD. Using a comprehensive phenotyping protocol capturing dimensional traits central to ASD and ADHD, the MAGNET project aims to identify data-driven clusters across ADHD-ASD spectra using deep phenotyping of symptoms and behaviours; investigate the degree of familiality for different dimensional ASD-ADHD phenotypes and clusters; and map the neurocognitive, brain imaging, and genetic correlates of these data-driven symptom-based clusters. METHODS: The MAGNET project will recruit 1,200 families with children who are either typically developing, or who display elevated ASD, ADHD, or ASD-ADHD traits, in addition to affected and unaffected biological siblings of probands, and parents. All children will be comprehensively phenotyped for behavioural symptoms, comorbidities, neurocognitive and neuroimaging traits and genetics. CONCLUSION: The MAGNET project will be the first large-scale family study to take a transdiagnostic approach to ASD-ADHD, utilising deep phenotyping across behavioural, neurocognitive, brain imaging and genetic measures.

Identifying and supporting autistic preschoolers and their families.

BACKGROUND: In Australia, preschoolers are being identified and diagnosed as autistic. OBJECTIVE: The aim of this article is to describe the different paths preschool children and their families can take from identification of developmental or behavioural concerns to ongoing support, intervention and healthcare. DISCUSSION: There are many ways in which general practitioners, working alongside other professionals and with relevant services, can assist each child and family.

Prevalence and Age of Onset of Regression in Children with Autism Spectrum Disorder: A Systematic Review and Meta-analytical Update.

A systematic review published in 2013 reported 32% of children on the autism spectrum experience skill loss, known as autistic regression. However, the frequency varied depending on definition and measures used to capture skills. Retrospective parent report and prospective observation indicate loss of language and/or social skills, with motor skills typically unaffected. Our aim was to update the prevalence and age of onset of autistic regression through a meta-analysis of the literature to understand if there have been changes to the reported onset and prevalence since 2010. A systematic literature search was conducted using Medline, Embase, PsycINFO, and the Cochrane Library databases and included studies published from 2010 onward. Risk of bias assessment was performed on included studies. A random effects model was used to calculate the pooled prevalence and age of onset of autistic regression. Ninety-seven studies were included in the systematic review, of which 75 studies involving 33,014 participants had sufficient data for meta-analytic syntheses. The pooled proportion of autistic regression was 30% (95% confidence interval [CI]: 27-32%) but heterogeneity was high (I2 = 96.91) and did not reduce with sensitivity or subgroup analyses based on study design or clinical differences, respectively. Prevalence varied according to risk of bias (low: 27%) and definition of regression (language: 20%, language/social: 40%, mixed: 30%, and unspecified: 27%). Weighted average age of onset was 19.8 months. Findings from this meta-analysis highlight the importance of developing a standardized definition of autistic regression, and tools to measure this at multiple time points during early childhood development. LAY SUMMARY: About a third of children with Autism Spectrum Disorder experience loss of skills, which is also known as autistic regression. This paper provides an update of the rate of autistic regression in children and the age when they first experience loss of skills, based on current studies. The findings from this review contribute to our understanding of the onset patterns of autistic regression. Unfortunately, studies are not sufficiently similar, making it difficult to provide clear answers on the exact timing or type of regression seen in different children.

Factors associated with autism spectrum disorder in children with tuberous sclerosis complex: a systematic review and meta-analysis.

AIM: To investigate associations between clinical factors and the development of autism spectrum disorder (ASD) in children with tuberous sclerosis complex (TSC), specifically seizures, electroencephalogram abnormalities, tubers and other neurostructural abnormalities, and genetic factors. METHOD: MEDLINE, Embase, PubMed, the Cochrane Library, and Web of Science were searched until January 2019. Studies that considered the predefined factors for development of ASD in children with TSC were included, following PRISMA-P guidelines. Two authors independently reviewed titles, abstracts, and full texts, extracted data, and assessed risk of bias. RESULTS: Forty-two studies with 3542 children with TSC were included. ASD was associated with a history of seizures (odds ratio [OR] 3.79, 95% confidence interval [CI] 1.77-8.14), infantile spasms compared with other seizure types (OR 3.04, 95% CI 2.17-4.27), onset of any seizure type during infancy (OR 2.65, 95% CI 1.08-6.54), and male sex (OR 1.62, 95% CI 1.23-2.14). There was no association with tuber number, tuber location, or genotype. INTERPRETATION: While a causal link between seizures and ASD in children with TSC cannot be inferred, a strong association between seizures and ASD in children with TSC, particularly with seizure onset during infancy and specifically infantile spasms, is present. Children with TSC and infant-onset seizures should be monitored for emerging features of ASD. What this paper adds Seizures and autism spectrum disorder (ASD) strongly associate in children with tuberous sclerosis complex (TSC). Infant-onset seizures and infantile spasms are particularly strongly associated with ASD in TSC.

FMR1 mRNA from full mutation alleles is associated with ABC-CFX scores in males with fragile X syndrome.

Fragile X syndrome (FXS) is caused by a hypermethylated full mutation (FM) expansion with ≥ 200 CGG repeats, and a decrease in FMR1 mRNA and its protein. However, incomplete silencing from FM alleles has been associated with more severe autism features in FXS males. This study compared scores on the Aberrant Behavior Checklist-Community-FXS version (ABC-CFX) in 62 males affected with FXS (3 to 32 years) stratified based on presence or absence of mosaicism and/or FMR1 mRNA silencing. Associations between ABC-CFX subscales and FMR1 mRNA levels, assessed using real-time PCR relative standard curve method, were also examined. The FXS group mosaic for premutation (PM: 55-199 CGGs) and FM alleles had lower irritability (p = 0.014) and inappropriate speech (p < 0.001) scores compared to males with only FM alleles and complete loss of FMR1 mRNA. The PM/FM mosaic group also showed lower inappropriate speech scores compared to the incomplete silencing (p = 0.002) group. Increased FMR1 mRNA levels were associated with greater irritability (p < 0.001), and lower health-related quality of life scores (p = 0.004), but only in the incomplete silencing FM-only group. The findings suggest that stratification based on CGG sizing and FMR1 mRNA levels may be warranted in future research and clinical trials utilising ABC-CFX subscales as outcome measures.

Rates and Stability of Mental Health Disorders in Children Born Very Preterm at 7 and 13 Years.

OBJECTIVES: Children born very preterm (VPT) are at an increased risk of developing mental health (MH) disorders. Our aim for this study was to assess rates of MH disorders in children born VPT and term at 13 years of age and stability of MH disorders between ages 7 and 13 years by using a diagnostic measure. METHODS: Participants were from the Victorian Infant Brain Study longitudinal cohort and included 125 children born VPT (<30 weeks' gestational age and/or <1250 g) and 49 children born term (≥37 weeks' gestational age) and their families. Participants were followed-up at both 7 and 13 years, and the Development and Well-Being Assessment was administered to assess for MH disorders. RESULTS: Compared with term peers, 13-year-olds born VPT were more likely to meet criteria for any MH disorder (odds ratio 5.9; 95% confidence interval 1.71-20.03). Anxiety was the most common disorder in both groups (VPT = 14%; term = 4%), whereas attention-deficit/hyperactivity disorder carried the greatest differential elevated risk (odds ratio 5.6; 95% confidence interval 0.71-43.80). Overall rates of MH disorders remained stable between 7 and 13 years, although at an individual level, many participants shifted in or out of diagnostic categories over time. CONCLUSIONS: Children born VPT show higher rates of MH disorders than their term peers, with changing trajectories over time. Findings highlight the importance of early identification and ongoing assessment to support those with MH disorders in this population.

Intellectual functioning and behavioural features associated with mosaicism in fragile X syndrome.

BACKGROUND: Fragile X syndrome (FXS) is a common cause of intellectual disability and autism spectrum disorder (ASD) usually associated with a CGG expansion, termed full mutation (FM: CGG ≥ 200), increased DNA methylation of the FMR1 promoter and silencing of the gene. Mosaicism for presence of cells with either methylated FM or smaller unmethylated pre-mutation (PM: CGG 55-199) alleles in the same individual have been associated with better cognitive functioning. This study compares age- and sex-matched FM-only and PM/FM mosaic individuals on intellectual functioning, ASD features and maladaptive behaviours. METHODS: This study comprised a large international cohort of 126 male and female participants with FXS (aged 1.15 to 43.17 years) separated into FM-only and PM/FM mosaic groups (90 males, 77.8% FM-only; 36 females, 77.8% FM-only). Intellectual functioning was assessed with age appropriate developmental or intelligence tests. The Autism Diagnostic Observation Schedule-2nd Edition was used to examine ASD features while the Aberrant Behavior Checklist-Community assessed maladaptive behaviours. RESULTS: Comparing males and females (FM-only + PM/FM mosaic), males had poorer intellectual functioning on all domains (p < 0.0001). Although females had less ASD features and less parent-reported maladaptive behaviours, these differences were no longer significant after controlling for intellectual functioning. Participants with PM/FM mosaicism, regardless of sex, presented with better intellectual functioning and less maladaptive behaviours compared with their age- and sex-matched FM-only counterparts (p < 0.05). ASD features were similar between FM-only and PM/FM mosaics within each sex, after controlling for overall intellectual functioning. CONCLUSIONS: Males with FXS had significantly lower intellectual functioning than females with FXS. However, there were no significant differences in ASD features and maladaptive behaviours, after controlling for intellectual functioning, independent of the presence or absence of mosaicism. This suggests that interventions that primarily target cognitive abilities may in turn reduce the severity of maladaptive behaviours including ASD features in FXS.

Autism: One or many spectrums?

Our conceptualisation of autism spectrum disorder has changed over time, with recent classifications reflecting a heterogeneous clinical presentation now regularly encountered in routine general paediatric practice. As the prevalence of autism and associated demands for services have increased so has research into understanding the cause and trials aimed at providing best care and intervention. However, the heterogeneity of autism has meant that no single aetiology can account for all differences in presentation, and not all children benefit from broad-based interventions. Now is the time to rethink how best to understand individual differences in order to focus research efforts and take steps towards more sophisticated strategies that go beyond the behaviours we look for when making an autism diagnosis. We suggest adopting a dimensional approach to autism assessment, with the consideration of eight spectrums of abilities, ways of thinking and behaviour. This eight-spectrum approach will assist clinicians to consider each individual's strengths and needs and personalise interventions and support accordingly. Profiling individual skills across these dimensions may also provide researchers with a greater capacity to link causal pathways with specific phenotypes, which is needed to develop precision medicine for autism.

Measurement properties of instruments that assess participation in young people with autism spectrum disorder: a systematic review.

AIM: To systematically review the measurement properties of instruments assessing participation in young people with autism spectrum disorder (ASD). METHOD: A search was performed in MEDLINE, PsycINFO, and PubMed combining three constructs ('ASD', 'test of participation', 'measurement properties'). Results were restricted to articles including people aged 6 to 29 years. The 2539 identified articles were independently screened by two reviewers. For the included articles, data were extracted using standard forms and their risk of bias was assessed. RESULTS: Nine studies (8 cross-sectional) met the inclusion criteria, providing information on seven different instruments. The total sample included 634 participants, with sex available for 600 (males=494; females=106) and age available for 570, with mean age for these participants 140.58 months (SD=9.11; range=36-624). Included instruments were the school function assessment, vocational index, children's assessment of participation and enjoyment/preferences for activities of children, experience sampling method, Pediatric Evaluation of Disability Inventory, Computer Adaptive Test, adolescent and young adult activity card sort, and Patient-Reported Outcomes Measurement Information System parent-proxy peer relationships. Seven studies assessed reliability and validity; good properties were reported for half of the instruments considered. Most studies (n=6) had high risk of bias. Overall the quality of the evidence for each tool was limited. INTERPRETATION: Validation of these instruments, or others that comprehensively assess participation, is needed. Future studies should follow recommended methodological standards. WHAT THIS PAPER ADDS: Seven instruments have been used to assess participation in young people with autism. One instrument, with excellent measurement properties in one study, does not comprehensively assess participation. Studies of three instruments that incorporate a more comprehensive assessment of participation have methodological limitations. Overall, limited evidence exists regarding measurement properties of participation assessments for young people with autism.

The influence of multiple birth and bereavement on maternal and family outcomes 2 and 7years after very preterm birth.

BACKGROUND: Psychological distress has been reported by mothers of infants born very preterm (VPT) and by mothers of multiples (twins and triplets). This study examined the influence of i) multiple birth and ii) bereavement associated with a multifetal pregnancy, on mental health, parenting stress and family functioning for mothers of children born VPT across early childhood. METHODS: Participants were 162 mothers of 194 infants (129 singletons, 65 multiples) born at <30weeks' gestation or with a birth weight<1250g who completed questionnaires when their children were two and seven years corrected age. Fifteen mothers (9%) experienced bereavement associated with a multifetal pregnancy. Maternal mental health was assessed using the General Health Questionnaire at two years and Hospital Anxiety and Depression Scale at seven years. Parenting stress and family functioning were assessed using the Parenting Stress Index and Family Assessment Device. RESULTS: Maternal mental health, stress and family functioning were similar in mothers of VPT singletons and multiples. However compared with mothers who had not experienced bereavement, mothers who had were 3.6 times [95% confidence interval (95% CI) 1.05, 12.5] more likely to report elevated anxiety symptoms and 3.6 times [95% CI 1.05, 12.3] more likely to report elevated depressive symptoms when their VPT child was seven years old. CONCLUSIONS: The results of this study highlight the need for monitoring and offering ongoing support to bereaved mothers with surviving VPT children. However, within the context of VPT birth, multiple birth does not increase the risk for maternal psychological distress in early childhood.

Parenting behavior at 2 years predicts school-age performance at 7 years in very preterm children.

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.

Neonatal brain abnormalities associated with autism spectrum disorder in children born very preterm.

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.

Psychiatric outcomes at age seven for very preterm children: rates and predictors.

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.