Precision therapy in the genetic epilepsies of childhood

Despite recent advances in both the understanding and treatment of the epilepsies, the rate of refractory epilepsy has remained static for many years. However, given our greater understanding of the aetiology and genetic basis of many paediatric and adult epilepsies, there is now scope to expand treatment. In this review, we discuss the current and potential use of precision medicine in the genetic epilepsies of childhood. We will discuss how optimal control and a reduction in the rate of refractory seizures using targeted therapy could be developed and assessed. We propose a six-tier approach to defining precision therapeutics in epilepsy and discuss how this can be incorporated into a clinical trial design. The lower tiers (1–2) represent therapies in common usage that we know work for certain epilepsy syndromes but do not precisely target the underlying problem. They work to reduce seizures but do not directly or effectively attenuate the developmental phenotype. The higher tiers (5–6) are currently purely speculative and look to a future with highly disease-specific therapies based on correction of underlying genomic and proteomic issues. In order to achieve this, scientists will have to embark on a ‘whole-omic’ approach to understand the underlying pathophysiology in order to design a precision therapy

Social communication skill attainment in babies born during the COVID-19 pandemic: a birth cohort study

Introduction: The SARS-CoV-2 (COVID-19) pandemic was managed with sustained mass lockdowns to prevent spread of COVID-19 infection. Babies born during the early stages of the pandemic missed the opportunity of meeting a normal social circle of people outside the family home. Methods: We compared 10 parentally reported developmental milestones at 12-month assessment in a cohort of 309 babies born at the onset of the pandemic (CORAL cohort) and 1629 babies from a historical birth cohort (BASELINE cohort recruited between 2008 and 2011). Results: Compared with a historical cohort, babies born into lockdown appeared to have some deficits in social communication. Fewer infants in the pandemic cohort had one definite and meaningful word (76.6% vs 89.3%), could point (83.8% vs 92.8%) or wave bye-bye (87.7% vs 94.4%) at 12-month assessment. Adjusted log-binomial regression analyses demonstrated significant differences in social communication in the CORAL cohort compared with the BASELINE cohort: one definite and meaningful word (relative risk (RR): 0.86 (95% CI: 0.80 to 0.92)), pointing (RR: 0.91 (95% CI: 0.86 to 0.96)) and waving bye-bye (RR: 0.94 (95% CI: 0.90 to 0.99)). Discussion: Parentally reported developmental outcomes in a birth cohort of babies born into lockdown during the COVID-19 pandemic may indicate some potential deficits in early life social communication. It must be noted that milestones are parentally reported and comparison is with a historical cohort with associated limitations. Further studies with standardised testing is required to validate these findings. Conclusion: Pandemic-associated social isolation may have impacted on the social communication skills in babies born during the pandemic compared with a historical cohort. Babies are resilient and inquisitive by nature, and it is hoped that with societal re-emergence and increase in social circles, their social communication skills will improve.</p

Parenting a newborn baby during the COVID-19 pandemic: a qualitative survey

Objective: The COVID-19 pandemic caused long periods of lockdown, social isolation and intense challenges for parents. This study examines parenting in an infant cohort born at the pandemic onset. Methods: The CORAL study is a prospective longitudinal observational study looking at allergy, immune function and neurodevelopmental outcome in babies born between March and May 2020. Demographic information was collected, babies were reviewed at 6-monthly intervals, and serology for COVID-19 infection was recorded. When babies were 12 months old, parents were asked for 3-5 words to describe raising a baby during the pandemic. Frequency of word usage was compared between first time parents and parents with other children, and parents of babies with and without a diagnosis of COVID-19 infection. Results: 354 babies were recruited to CORAL study. Social circles were small. At 6 months the median number of people (including parents) who had kissed the baby was 3, and by 12 months one-quarter of babies had never met another child of similar age. 304 parents completed the word choice. Commonly reported words were lonely (44.4%), isolating (31.9%) and strong bond (15.8%). 12 of those 304 babies had COVID-19 in their first year of life and there was no significant difference in reported negative or positive word number compared with parents of babies without a COVID-19 infection, or by first time parents or those who already had children. Conclusion: The lockdowns and social restrictions made raising an infant challenging for all parents in Ireland. It is important parents know this was a shared experience.</p

Developmental and behavioural outcomes at 2 years in babies born during the COVID-19 pandemic: communication concerns in a pandemic birth cohort

Introduction: The CORAL (Impact of Corona Virus Pandemic on Allergic and Autoimmune Dysregulation in Infants Born During Lockdown) study reported a reduction in social communication milestones in 12-month-old infants born into the COVID-19 pandemic. Aims: To look at 24-month developmental and behavioural outcomes in the CORAL cohort. Design: The CORAL study is a longitudinal prospective observational study of Irish infants born in the first 3 months of the pandemic. At 24 months of age, the Ages and Stages Developmental Questionnaire (ASQ24) and the Child Behaviour Checklist (CBCL) were completed and compared with prepandemic BASELINE (Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Impact) cohort. Results: 917 babies (312 CORAL infants and 605 BASELINE infants) were included. At 24 months of age, infants in the CORAL and BASELINE cohorts had similar developmental ASQ24 scores in fine motor, problem solving and personal and social domains but ASQ24 communication scores were significantly lower in the CORAL group compared with the BASELINE cohort (mean (SD) 49.5 (15.1) vs 53.7 (11.6), p Conclusion: 24-month-old pandemic-born infants had largely similar developmental and behavioural scores compared with their prepandemic counterparts. Concerns have been raised in the communication developmental domain.</p

Infants born during the Covid-19 pandemic have less interest in masked faces than unmasked faces

The COVID-19 pandemic was managed with lockdown, social distancing, mask-wearing and vaccination. Babies experienced societal isolation and encountered mask-wearing. There was speculation about whether COVID-19 mitigation measures, including mask-wearing, would impact child development. Deficits were identified in early communication skills among babies aged up to 24 months assessed during the pandemic. The CORAL Study is a longitudinal study of over 350 Irish infants born into the pandemic.4 We have previously demonstrated that CORAL infants had limited social circles and a reduction in social/communication skills relative to a historical cohort at 12 and 24 months of age.3 4 We used eye-tracking technology to determine where 18-month-old CORAL infants fixed their gaze when looking at unmasked and masked adults. </p

Association between gut microbiota development and allergy in infants born during pandemic-related social distancing restrictions

Background: Several hypotheses link reduced microbial exposure to increased prevalence of allergies. Here we capitalize on the opportunity to study a cohort of infants (CORAL), raised during COVID-19 associated social distancing measures, to identify the environmental exposures and dietary factors that contribute to early life microbiota development and to examine their associations with allergic outcomes. Methods: Fecal samples were sequenced from infants at 6 (n = 351) and repeated at 12 (n = 343) months, using 16S sequencing. Published 16S data from pre-pandemic cohorts were included for microbiota comparisons. Online questionnaires collected epidemiological information on home environment, healthcare utilization, infant health, allergic diseases, and diet. Skin prick testing (SPT) was performed at 12 (n = 343) and 24 (n = 320) months of age, accompanied by atopic dermatitis and food allergy assessments. Results: The relative abundance of bifidobacteria was higher, while environmentally transmitted bacteria such as Clostridia was lower in CORAL infants compared to previous cohorts. The abundance of multiple Clostridia taxa correlated with a microbial exposure index. Plant based foods during weaning positively impacted microbiota development. Bifidobacteria levels at 6 months of age, and relative abundance of butyrate producers at 12 months of age, were negatively associated with AD and SPT positivity. The prevalence of allergen sensitization, food allergy, and AD did not increase over pre-pandemic levels. Conclusions: Environmental exposures and dietary components significantly impact microbiota community assembly. Our results also suggest that vertically transmitted bacteria and appropriate dietary supports may be more important than exposure to environmental microbes alone for protection against allergic diseases in infancy.</p