Paediatrics (RCH) - Research Publications
Now showing items 1-12 of 4105
The education word gap emerges by 18 months: findings from an Australian prospective study
BACKGROUND: The idea of the '30 million word gap' suggests families from more socioeconomically advantaged backgrounds engage in more verbal interactions with their child than disadvantaged families. Initial findings from the Language in Little Ones (LiLO) study up to 12 months showed no word gap between maternal education groups. METHODS: Families with either high or low maternal education were purposively recruited into a five-year prospective study. We report results from the first three waves of LiLO when children were 6, 12 and 18 months old. Day-long audio recordings, obtained using the Language Environment Analysis software, provided counts of adult words spoken to the child, child vocalizations and conversational turns. RESULTS: By the time children were 18 months old all three measures of talk were 0.5 to 0.7 SD higher among families with more education, but with large variation within education groups. Changes in talk from 6 to 18 months highlighted that families from low educated backgrounds were decreasing the amount they spoke to their children (- 4219.54, 95% CI -6054.13, - 2384.95), compared to families from high educated backgrounds who remained relatively stable across this age period (- 369.13, 95% CI - 2344.57, 1606.30). CONCLUSIONS: The socioeconomic word gap emerges between 12 and 18 months of age. Interventions to enhance maternal communication, child vocalisations and vocabulary development should begin prior to 18 months.
Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network.
(Springer Science and Business Media LLC, 2021-06-02)
Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.
Mapping inequalities in exclusive breastfeeding in low- and middle-income countries, 2000-2018.
(Springer Science and Business Media LLC, 2021-08)
Exclusive breastfeeding (EBF)-giving infants only breast-milk for the first 6 months of life-is a component of optimal breastfeeding practices effective in preventing child morbidity and mortality. EBF practices are known to vary by population and comparable subnational estimates of prevalence and progress across low- and middle-income countries (LMICs) are required for planning policy and interventions. Here we present a geospatial analysis of EBF prevalence estimates from 2000 to 2018 across 94 LMICs mapped to policy-relevant administrative units (for example, districts), quantify subnational inequalities and their changes over time, and estimate probabilities of meeting the World Health Organization's Global Nutrition Target (WHO GNT) of ≥70% EBF prevalence by 2030. While six LMICs are projected to meet the WHO GNT of ≥70% EBF prevalence at a national scale, only three are predicted to meet the target in all their district-level units by 2030.
Harvard Medical School Department of Global Health and Social Medicine COVID-19 seminar series: COVID and surgical, anesthetic and obstetric care.
(Springer Science and Business Media LLC, 2021-09-23)
On May 21, 2020, the Harvard Program in Global Surgery and Social Change (PGSSC) hosted a webinar as part of the Harvard Medical School Department of Global Health and Social Medicine's COVID-19 webinar series. The goal of PGSSC's virtual webinar was to share the experiences of surgical, anesthesia, and obstetric (SAO) providers on the frontlines of the COVID pandemic, from both high-income countries (HICs), such as the United States and the United Kingdom, as well as low- and middle-income countries (LMICs). Providers shared not only their experiences delivering SAO care during this global pandemic, but also solutions and innovations they and their colleagues developed to address these new challenges. Additionally, the seminar explored the relationship between surgery and health system strengthening and pandemic preparedness, and outlined the way forward, including a roadmap for prioritization and investment in surgical system strengthening. Throughout the discussion, other themes emerged as well, such as the definition of elective surgery and its implications during a persistent global pandemic, the safe and ethical reintroduction of surgical services, and the social inequities exposed by the stress placed on health systems by COVID-19. These proceedings document the perspectives shared by participants through their invited lectures as well as through the panel discussion at the end of the seminar.
Chimeric Antigen Receptor T cell Therapy and the Immunosuppressive Tumor Microenvironment in Pediatric Sarcoma
Sarcomas are a diverse group of bone and soft tissue tumors that account for over 10% of childhood cancers. Outcomes are particularly poor for children with refractory, relapsed, or metastatic disease. Chimeric antigen receptor T (CAR T) cells are an exciting form of adoptive cell therapy that potentially offers new hope for these children. In early trials, promising outcomes have been achieved in some pediatric patients with sarcoma. However, many children do not derive benefit despite significant expression of the targeted tumor antigen. The success of CAR T cell therapy in sarcomas and other solid tumors is limited by the immunosuppressive tumor microenvironment (TME). In this review, we provide an update of the CAR T cell therapies that are currently being tested in pediatric sarcoma clinical trials, including those targeting tumors that express HER2, NY-ESO, GD2, EGFR, GPC3, B7-H3, and MAGE-A4. We also outline promising new CAR T cells that are in pre-clinical development. Finally, we discuss strategies that are being used to overcome tumor-mediated immunosuppression in solid tumors; these strategies have the potential to improve clinical outcomes of CAR T cell therapy for children with sarcoma.
Teach-Back in Interpreter-Mediated Consultations: Reflections from a Case Study.
(SLACK, Inc., 2021-07)
BACKGROUND: Women with a refugee background and their families who have settled in a new country can be expected to have low health literacy, and this may be a contributing factor to poor perinatal outcomes. Brief description of activity: Effective communication is critical for meaningful engagement with patients. Teach-Back is an interactive tool that can assist health professionals confirm whether they are communicating effectively so they are understood and their patients can apply health information. However, evidence for its effectiveness in interpreter-mediated appointments is lacking. IMPLEMENTATION: An antenatal clinic caring for women with a refugee background provided an opportunity to explore the benefits and challenges of using Teach-Back with this population. Staff had access to informal on-site training on health literacy and Teach-Back, tried using Teach-Back in their clinical work, and were then asked to provide feedback on what it was like using Teach-Back. RESULTS: This case study identified several challenges when applying Teach-Back in interpreter-mediated antenatal health care appointments associated with differing cultural nuances and cultural practices. LESSONS LEARNED: Building interpersonal and cross-cultural communication capabilities among health professionals is essential in advancing health literacy workforce practice to improve the health literacy of non-English speaking refugee communities. Although Teach-Back may have the potential to be a powerful tool in promoting the health literacy of these women during pregnancy, further research is required to ensure that its use promotes safe and equitable health care. [HLRP: Health Literacy Research and Practice. 2021;5(3):e256-e261.] Plain Language Summary: This article reports a case study of using Teach-Back in pregnancy appointments involving a midwife and an interpreter. Several challenges for using Teach-Back were identified due to differences in cross-cultural communication. Supporting clinicians and interpreters to work together to implement Teach-Back is required to improve cross-cultural communication and women's health literacy.
Study protocol: childhood outcomes of fetal genomic variants: the PrenatAL Microarray (PALM) cohort study
BACKGROUND: The implementation of genomic testing in pregnancy means that couples have access to more information about their child's genetic make-up before birth than ever before. One of the resulting challenges is the management of genetic variations with unclear clinical significance. This population-based study will help to close this critical knowledge gap through a multidisciplinary cohort study of children with and without genomic copy number variants (CNVs) diagnosed before birth. By comparing children with prenatally-ascertained CNVs to children without a CNV, we aim to (1) examine their developmental, social-emotional and health status; (2) measure the impact of prenatal diagnosis of a CNV on maternal perceptions of child health, behavior and development; and (3) determine the proportion of prenatally-ascertained CNVs of unknown or uncertain significance that are reclassified as benign or pathogenic after 2 or more years. METHODS: This study will establish and follow up a cohort of mother-child pairs who have had a prenatal diagnosis with a chromosomal microarray from 2013-2019 in the Australian state of Victoria. Children aged 12 months to 7 years will be assessed using validated, age-appropriate measures. The primary outcome measures will be the Wechsler Preschool and Primary Scale of Intelligence IV (WPSSI-IV) IQ score (2.5 to 7 year old's), the Ages and Stages Questionnaire (12-30 months old), and the Brief Infant- Toddler Social and Emotional Assessment (BITSEA) score. Clinical assessment by a pediatrician will also be performed. Secondary outcomes will be scores obtained from the: Vineland Adaptive Behavior Scale, Maternal Postnatal Attachment Questionnaire, the Vulnerable Child Scale, Profile of Mood States, Parent Sense of Competence Scale. A descriptive analysis of the reclassification rates of CNVs after ≥2 years will be performed. DISCUSSION: This study protocol describes the first Australian cohort study following children after prenatal diagnostic testing with chromosomal microarray. It will provide long-term outcomes of fetal genomic variants to guide evidence-based pre-and postnatal care. This, in turn, will inform future efforts to mitigate the negative consequences of conveying genomic uncertainty during pregnancy. TRIAL REGISTRATION: ACTRN12620000446965p ; Registered on April 6, 2020.
Children and Adults in a Household Cohort Study Have Robust Longitudinal Immune Responses Following SARS-CoV-2 Infection or Exposure
(FRONTIERS MEDIA SA, 2021-10-13)
Children have reduced severity of COVID-19 compared to adults and typically have mild or asymptomatic disease. The immunological mechanisms underlying these age-related differences in clinical outcomes remain unexplained. Here, we quantify 23 immune cell populations in 141 samples from children and adults with mild COVID-19 and their PCR-negative close household contacts at acute and convalescent time points. Children with COVID-19 displayed marked reductions in myeloid cells during infection, most prominent in children under the age of five. Recovery from infection in both children and adults was characterised by the generation of CD8 TCM and CD4 TCM up to 9 weeks post infection. SARS-CoV-2-exposed close contacts also had immunological changes over time despite no evidence of confirmed SARS-CoV-2 infection on PCR testing. This included an increase in low-density neutrophils during convalescence in both exposed children and adults, as well as increases in CD8 TCM and CD4 TCM in exposed adults. In comparison to children with other common respiratory viral infections, those with COVID-19 had a greater change in innate and T cell-mediated immune responses over time. These findings provide new mechanistic insights into the immune response during and after recovery from COVID-19 in both children and adults.
Headache in ADHD as comorbidity and a side effect of medications: a systematic review and meta-analysis
(CAMBRIDGE UNIV PRESS, 2022-01-01)
There is mixed evidence on the association between headache and attention-deficit/hyperactivity disorder (ADHD), as well as headache and ADHD medications. This systematic review and meta-analysis investigated the co-occurrence of headache in children with ADHD, and the effects of ADHD medications on headache. Embase, Medline and PsycInfo were searched for population-based and clinical studies comparing the prevalence of headache in ADHD and controls through January 26, 2021. In addition, we updated the search of a previous systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs) on ADHD medications on June 16, 2020. Trials of amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with a placebo arm and reporting data on headache as an adverse event, were included. Thirteen epidemiological studies and 58 clinical trials were eligible for inclusion. In epidemiological studies, a significant association between headache and ADHD was found [odds ratio (OR) = 2.01, 95% confidence interval (CI) = 1.63-2.46], which remained significant when limited to studies reporting ORs adjusted for possible confounders. The pooled prevalence of headaches in children with ADHD was 26.6%. In RCTs, three ADHD medications were associated with increased headache during treatment periods, compared to placebo: atomoxetine (OR = 1.29, 95% CI = 1.06-1.56), guanfacine (OR = 1.43, 95% CI = 1.12-1.82), and methylphenidate (OR = 1.33, 95% CI = 1.09-1.63). The summarized evidence suggests that headache is common in children with ADHD, both as part of the clinical presentation as such and as a side effect of some standard medications. Monitoring and clinical management strategies of headache in ADHD, in general, and during pharmacological treatment are recommended.
Mapping Pulmonary and Systemic Inflammation in Preschool Aged Children With Cystic Fibrosis
(FRONTIERS MEDIA SA, 2021-10-15)
The immune landscape of the paediatric respiratory system remains largely uncharacterised and as a result, the mechanisms of globally important childhood respiratory diseases remain poorly understood. In this work, we used high parameter flow cytometry and inflammatory cytokine profiling to map the local [bronchoalveolar lavage (BAL)] and systemic (whole blood) immune response in preschool aged children with cystic fibrosis (CF) and aged-matched healthy controls. We demonstrate that children with CF show pulmonary infiltration of CD66b+ granulocytes and increased levels of MIP-1α, MIG, MCP-1, IL-8, and IL-6 in BAL relative to healthy control children. Proportions of systemic neutrophils positively correlated with age in children with CF, whilst systemic CD4 T cells and B cells were inversely associated with age. Inflammatory cells in the BAL from both CF and healthy children expressed higher levels of activation and migration markers relative to their systemic counterparts. This work highlights the utility of multiplex immune profiling and advanced analytical pipelines to understand mechanisms of lung disease in childhood.
The management of ADHD in children and adolescents: bringing evidence to the clinic: perspective from the European ADHD Guidelines Group (EAGG)
ADHD is the most common neurodevelopmental disorder presenting to child and adolescent mental health, paediatric, and primary care services. Timely and effective interventions to address core ADHD symptoms and co-occurring problems are a high priority for healthcare and society more widely. While much research has reported on the benefits and adverse effects of different interventions for ADHD, these individual research reports and the reviews, meta-analyses and guidelines summarizing their findings are sometimes inconsistent and difficult to interpret. We have summarized the current evidence and identified several methodological issues and gaps in the current evidence that we believe are important for clinicians to consider when evaluating the evidence and making treatment decisions. These include understanding potential impact of bias such as inadequate blinding and selection bias on study outcomes; the relative lack of high-quality data comparing different treatments and assessing long-term effectiveness, adverse effects and safety for both pharmacological and non-pharmacological treatments; and the problems associated with observational studies, including those based on large national registries and comparing treatments with each other. We highlight key similarities across current international clinical guidelines and discuss the reasons for divergence where these occur. We discuss the integration of these different perspective into a framework for person/family-centered evidence-based practice approach to care that aims to achieve optimal outcomes that prioritize individual strengths and impairments, as well as the personal treatment targets of children and their families. Finally, we consider how access to care for this common and impairing disorder can be improved in different healthcare systems.