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Aim: To compare the mental health and neurodevelopmental profiles of school‐age children born very preterm, with and without an anxiety disorder, and to identify neonatal medical, psychosocial, and concurrent neurodevelopmental correlates. Method: A regional cohort of 102 (51 males, 51 females) children born very preterm (mean [SD] gestation at birth=28wks [2], range=23–31wks) was studied from birth to age 9 years alongside a comparison group of 109 (58 males, 51 females) children born at term (mean [SD] gestation at birth=40wks [1], range=38–41wks). At age 9 years, all children underwent a neurodevelopmental evaluation while parents were interviewed using the Development and Well‐Being Assessment to diagnose a range of DSM‐IV childhood psychiatric disorders. Detailed information was also available about the children's neonatal medical course and postnatal psychosocial environment, including maternal mental health and parenting. Results: At age 9 years, 21% (n=21) of very preterm and 13% (n=14) of term‐born children met diagnostic criteria for an anxiety disorder. Clinically‐anxious children born very preterm were characterized by higher rates of comorbid mental health (odds ratio [OR]=11.5, 95% confidence interval [CI]=3.8–34.7), social (OR=6.2, 95% CI=2.1–18.4), motor (OR=4.4, 95% CI=1.6–12.2), and cognitive (OR=2.6, 95% CI=1.0–7.0) problems than those without an anxiety disorder. Concurrent maternal mental health and child social difficulties were the strongest independent correlates of early‐onset child anxiety disorders. Interpretation: Children born very preterm who developed an early‐onset anxiety disorder were subject to high rates of comorbid problems. Findings highlight the importance of addressing both maternal and child mental health issues to optimize outcomes in this high‐risk population. What this paper addsOne out of five school‐age children born very preterm are likely to meet DSM‐IV diagnostic criteria for an anxiety disorder.Half of these children born very preterm with an early‐onset anxiety disorder have comorbid attention‐deficit/hyperactivity disorder.Other neurodevelopmental correlates of early‐onset anxiety disorders include lower cognitive ability, motor problems, and peer social difficulties.Concurrent maternal mental health and child social adjustment problems were the strongest correlates of early‐onset anxiety disorder risk among children born very preterm. What this paper adds: One out of five school‐age children born very preterm are likely to meet DSM‐IV diagnostic criteria for an anxiety disorder.Half of these children born very preterm with an early‐onset anxiety disorder have comorbid attention‐deficit/hyperactivity disorder.Other neurodevelopmental correlates of early‐onset anxiety disorders include lower cognitive ability, motor problems, and peer social difficulties.Concurrent maternal mental health and child social adjustment problems were the strongest correlates of early‐onset anxiety disorder risk among children born very preterm. This article is commented on by Hunter on page 892 of this issue. [ABSTRACT FROM AUTHOR]

Rett syndrome (RTT) is an X-linked neurogenetic disorder caused by mutations of the MECP2 (methyl-CpG-binding protein 2) gene. Over two decades of work established MeCP2 as a protein with pivotal roles in the regulation of the epigenome, neuronal physiology, synaptic maintenance, and behaviour. Given the genetic aetiology of RTT and the proof of concept of its reversal in a mouse model, considerable efforts have been made to design therapeutic approaches to re-express MeCP2. By being at the forefront of the development of innovative gene therapies, research on RTT is of paramount importance for the treatment of monogenic neurological diseases. Here we discuss the recent advances and challenges of promising genetic strategies for the treatment of RTT including gene replacement therapies, gene/RNA editing strategies, and reactivation of the silenced X chromosome. WHAT THIS PAPER ADDS: Recent advances shed light on the promises of gene replacement therapy with new vectors designed to control the levels of MeCP2 expression. New developments in DNA/RNA editing approaches or reactivation of the silenced X chromosome open the possibility to re-express the native MeCP2 locus at endogenous levels. Current strategies still face limitations in transduction efficiency and future work is needed to improve brain delivery.

Aim: To investigate the efficacy of psychological interventions delivered to mothers of young children with autism spectrum disorder (ASD) in improving maternal mental health and the parent–child relationship. Method: Electronic databases were searched from inception to December 2021. Studies were included if they were randomized controlled trials (RCTs) of psychological interventions that targeted maternal mental health (primary outcome) and/or the parent–child relationship (secondary outcome), delivered to mothers of children (mean age < 60 months) with ASD. Meta‐analyses of three parent mental health outcomes (stress, depressive symptomatology, and general mental health) and seven parent–child relationship outcomes (parent responsiveness, affect, directiveness, non‐directiveness, child initiation, infant positive affect, and infant attentiveness) were conducted using both mean and standardized mean differences. Results: Thirty‐two RCTs met the inclusion criteria (2336 participants). Six RCTs showed improved maternal mental health (Cohen's d = 0.41–1.15), with moderate certainty of evidence for improvement in parental stress. There was low and high certainty of evidence of treatment effect on parental depressive symptoms and general mental health respectively, which did not show significant treatment effects post‐intervention. Seventeen RCTs showed improved parent–child relationship (d = 0.33–2.28; low certainty of evidence). Interpretation: Results demonstrated that parenting interventions promoting responsiveness had the largest positive effect on the parent–child relationship and a moderate effect on overall parenting stress; however, the studies were heterogeneous, making it difficult to identify the intervention components that were responsible for the positive treatment effects. There was no significant treatment effect for studies targeting depression or general mental health, likely due to the lack of an interventional component directly targeting mental health. [ABSTRACT FROM AUTHOR]

Aim: To identify the highest‐priority clinical research areas related to children with neurological impairment and medical complexity among clinicians and caregivers. Method: A modified, three‐stage Delphi study using online surveys and guided by a steering committee was completed. In round 1, clinicians and family caregivers suggested clinical topics and related questions that require research to support this subgroup of children. After refinement of the suggestions by the steering committee, participants contributed to 1 (family caregivers) or 2 (clinicians) subsequent rounds to develop a prioritized list. Results: A diverse international expert panel consisting of 49 clinicians and 12 family caregivers provided 601 responses. Responses were distilled into 26 clinical topics comprising 126 related questions. The top clinical topics prioritized for research were irritability and pain, child mental health, disorders of tone, polypharmacy, sleep, aspiration, behavior, dysautonomia, and feeding intolerance. The clinician expert panel also prioritized 10 specific research questions. Interpretation: Study findings support a research agenda for children with neurological impairment and medical complexity focused on addressing clinical questions, prioritized by an international group of clinicians and caregivers. This original article is commented by Becker‐Barroso on page 145 of this issue. [ABSTRACT FROM AUTHOR]