Macrocephaly, which is defined as a head circumference greater than or equal to + 2 standard deviations, is a feature commonly observed in children with developmental delay and/or autism spectrum disorder. Although PTEN is a well-known gene identified in patients with this syndromic presentation, other genes in the PI3K-AKT-mTOR signalling pathway have also recently been suggested to have important roles. The aim of this study is to characterise the mutation spectrum of this group of patients. We performed whole-exome sequencing of 21 patients with macrocephaly and developmental delay/autism spectrum disorder. Sources of genomic DNA included blood, buccal mucosa and saliva. Germline mutations were validated by Sanger sequencing, whereas somatic mutations were validated by droplet digital PCR. We identified ten pathogenic/likely pathogenic mutations in PTEN (n = 4), PIK3CA (n = 3), MTOR (n = 1) and PPP2R5D (n = 2) in ten patients. An additional PTEN mutation, which was classified as variant of unknown significance, was identified in a patient with a pathogenic PTEN mutation, making him harbour bi-allelic germline PTEN mutations. Two patients harboured somatic PIK3CA mutations, and the level of somatic mosaicism in blood DNA was low. Patients who tested positive for mutations in the PI3K-AKT-mTOR pathway had a lower developmental quotient than the rest of the cohort (DQ = 62.8 vs. 76.1, p = 0.021). Their dysmorphic features were non-specific, except for macrocephaly. Among the ten patients with identified mutations, brain magnetic resonance imaging was performed in nine, all of whom showed megalencephaly. We identified mutations in the PI3K-AKT-mTOR signalling pathway in nearly half of our patients with macrocephaly and developmental delay/autism spectrum disorder. These patients have subtle dysmorphic features and mild developmental issues. Clinically, patients with germline mutations are difficult to distinguish from patients with somatic mutations, and therefore, sequencing of buccal or saliva DNA is important to identify somatic mosaicism. Given the high diagnostic yield and the management implications, we suggest implementing comprehensive genetic testing in the PI3K-AKT-mTOR pathway in the clinical evaluation of patients with macrocephaly and developmental delay and/or autism spectrum disorder.

Depression prevention among adolescents is crucial for reducing the global disease burden. Internet-based depression prevention approaches are found to be effective but they were mostly evaluated in a Western context. Grasping the Opportunity is a Chinese Internet intervention, which was translated and modified from CATCH-IT developed in the West. We aimed to evaluate the effectiveness of Grasp the Opportunity in reducing depressive symptoms in Chinese adolescents. In this randomized controlled trial, Chinese adolescents aged 13 to 17 years with mild-to-moderate depressive symptoms were recruited from three secondary schools in Hong Kong. The participants (n = 257) were randomly assigned to receive either intervention or attention control. The primary outcome was the improvement in depressive symptoms according to the revised Center for Epidemiologic Studies Depression Scale (CESD-R) at the 12-month follow-up. Analyses were performed using intention to treat (ITT). The participants were randomly assigned to receive the intervention (n = 130) or attention control (n = 127). Follow-up data were obtained from 250 (97%) participants. Only 26 (10%) participants completed the intervention. Compared to the attention control, Grasp the Opportunity led to reductions in depressive symptoms at the 12-month follow-up with a medium effect size using ITT analysis (mean difference 2.6, 95% CI 0.59–5.55, effect size d = 0.36). Grasp the Opportunity is effective in reducing depressive symptoms in Chinese adolescents over a long follow-up period. Poor completion rate is the major challenge in the study.

There has been a rapid surge of hospitalization due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants globally. The severity of Omicron BA.2 in unexposed, unvaccinated, hospitalized children is unknown. We investigated the severity and clinical outcomes of COVID-19 infection during the Omicron wave in uninfected, unvaccinated hospitalized children and in comparison with influenza and parainfluenza viral infections. This population-based study retrieved data from the HK territory-wide CDARS database of hospitalisations in all public hospitals and compared severe outcomes for the Omicron BA.2-dominant fifth wave (5–28 February 2022, n = 1144), and influenza and parainfluenza viruses (1 January 2015–31 December 2019, n = 32212 and n = 16423, respectively) in children 0–11 years old. Two deaths (0.2%) out of 1144 cases during the initial Omicron wave were recorded. Twenty-one (1.8%) required PICU admission, and the relative risk was higher for Omicron than influenza virus (n = 254, 0.8%, adjusted RR = 2.1, 95%CI 1.3–3.3, p = 0.001). The proportion with neurological complications was 15.0% (n = 171) for Omicron, which was higher than influenza and parainfluenza viruses (n = 2707, 8.4%, adjusted RR = 1.6, 95%CI 1.4–1.9 and n = 1258, 7.7%, adjusted RR = 1.9, 95%CI 1.6–2.2, p < 0.001 for both, respectively). Croup occurred for Omicron (n = 61, 5.3%) more than influenza virus (n = 601, 1.9%, adjusted RR = 2.0, 95%CI 1.5–2.6, p < 0.001) but not parainfluenza virus (n = 889, 5.4%). Our findings showed that for hospitalized children who had no past COVID-19 or vaccination, Omicron BA.2 was not mild. Omicron BA.2 appeared to be more neuropathogenic than influenza and parainfluenza viruses. It targeted the upper airways more than influenza virus.

Nutritional supplements may be important on cognition but the evidence is heterogeneous. This meta-analysis aimed (1) to determine whether nutritional supplements provided to pregnant women or young children could improve cognitive development of children in developing countries, and (2) to explore how supplementation characteristics could improve children’s cognitive outcomes. This meta-analysis examined nutritional supplementation studies in 9 electronic databases and 13 specialist websites. Experimental studies were included if they were published from 1992 to 2016, were conducted in developing countries, had nutritional supplementation for pregnant women or children aged ≤8, and reported effect sizes on cognitive outcomes. Interventions with confounded components, such as stimulation and parenting, were excluded. 67 interventions (48 studies) for 29814 children from 20 developing countries were evaluated. Childhood nutritional supplementation could improve children’s cognitive development (d 0.08, 95% CI 0.03–0.13) and those with ≥5 nutrients was particularly beneficial (0.15, 0.08–0.22). Antenatal supplementation did not improve cognitive development (0.02, -0.01 to 0.06) except for those implemented in the first trimester (0.15, 0.03–0.28). In conclusion, childhood nutritional supplementation was beneficial to cognitive development but could be optimised by providing multiple nutrients; antenatal supplementation should target pregnancy women in the first trimester for better cognitive benefits.

Despite concerns about the negative effects of social distancing and prolonged school closures on children’s lifestyle and physical activity (PA) during the COVID-19 pandemic, robust evidence is lacking on the impact of the pandemic-related school closures and social distancing on children’s wellbeing and daily life. This study aimed to examine changes in the PA levels, sleep patterns, and screen time of school-aged children during the different phases of the COVID-19 outbreak in Hong Kong using a repeated cross-sectional design. School students (grades 1 to 12) were asked to report their daily electronic device usage and to fill in a sleep diary, recording their daily sleep onset and wake-up time. They were equipped with a PA monitor, Actigraph wGT3X-BT, to obtain objective data on their PA levels and sleep patterns. Students were recruited before the pandemic (September 2019–January 2020; n = 577), during school closures (March 2020–April 2020; n = 146), and after schools partially reopened (October 2020–July 2021; n = 227). Our results indicated lower PA levels, longer sleep duration, and longer screen time among participants recruited during school closures than those recruited before the COVID-19 outbreak. Primary school students were found to sleep on average for an extra hour during school closures. The later sleep onset and increased screen time documented during school closures persisted when schools partially reopened. Our findings illustrate the significant impact of social distancing policies during the COVID-19 pandemic on the sleep pattern, screen time, and PA level in school-aged children in Hong Kong. Professionals should urgently reinforce the importance of improving physically activity, good sleep hygiene, and regulated use of electronic devices for parents and school-aged children during this unprecedented time.