17q21 Variants Disturb Mucosal Host Defense in Childhood Asthma.

Rationale: The strongest genetic risk factor for childhood-onset asthma, the 17q21 locus, is associated with increased viral susceptibility and disease-promoting processes.Objectives: To identify biological targets underlying the escalated viral susceptibility associated with the clinical phenotype mediated by the 17q21 locus.Methods: Genome-wide transcriptome analysis of nasal brush samples from 261 children (78 healthy, 79 with wheezing at preschool age, 104 asthmatic) within the ALLIANCE (All-Age-Asthma) cohort, with a median age of 10.0 (range, 1.0-20.0) years, was conducted to explore the impact of their 17q21 genotype (SNP rs72163891). Concurrently, nasal secretions from the same patients and visits were collected, and high-sensitivity mesoscale technology was employed to measure IFN protein levels.Measurements and Main Results: This study revealed that the 17q21 risk allele induces a genotype- and asthma/wheeze phenotype-dependent enhancement of mucosal GSDMB expression as the only relevant 17q21-encoded gene in children with preschool wheeze. Increased GSDMB expression correlated with the activation of a type-1 proinflammatory, cell-lytic immune, and natural killer signature, encompassing key genes linked to an IFN type-2-signature (IFNG, CXCL9, CXCL10, KLRC1, CD8A, GZMA). Conversely, there was a reduction in IFN type 1 and type 3 expression signatures at the mRNA and protein levels.Conclusions: This study demonstrates a novel disease-driving mechanism induced by the 17q21 risk allele. Increased mucosal GSDMB expression is associated with a cell-lytic immune response coupled with compromised airway immunocompetence. These findings suggest that GSDMB-related airway cell death and perturbations in the mucosal IFN signature account for the increased vulnerability of 17q21 risk allele carriers to respiratory viral infections during early life, opening new options for future biological interventions.The All-Age-Asthma (ALLIANCE) cohort is registered at www.clinicaltrials.gov (pediatric arm, NCT02496468).

Key risk factors of asthma-like symptoms are mediated through infection burden in early childhood.

BACKGROUND: Risk factors of asthma-like symptoms in childhood may act through an increased infection burden because infections often trigger these symptoms. OBJECTIVE: We sought to investigate whether the effect of established risk factors of asthma-like episodes in early childhood is mediated through burden and subtypes of common infections. METHODS: The study included 662 children from the Copenhagen Prospective Studies on Asthma in Childhood 2010 mother-child cohort, in which infections were registered prospectively in daily diaries from age 0 to 3 years. The association between established risk factors of asthma-like episodes and infection burden was analyzed by quasi-Poisson regressions, and mediation analyses were performed for significant risk factors. RESULTS: In the first 3 years of life, the children experienced a median of 16 (interquartile range, 12-23) infectious episodes. We found that the infection burden significantly (PACME < .05) mediated the association of maternal asthma (36.6% mediated), antibiotics during pregnancy (47.3%), siblings at birth (57.7%), an asthma exacerbation polygenic risk score (30.6%), and a bacterial airway immune score (80.2%) with number of asthma-like episodes, whereas the higher number of episodes from male sex, low birth weight, low gestational age, and maternal antibiotic use after birth was not mediated through an increased infection burden. Subtypes of infections driving the mediation were primarily colds, pneumonia, gastroenteritis, and fever, but not acute otitis media or acute tonsillitis. CONCLUSIONS: Several risk factors of asthma-like symptoms in early childhood act through an increased infection burden in the first 3 years of life. Prevention of infectious episodes may therefore be beneficial to reduce the burden of asthma-like symptoms in early childhood.

Relationships Between Schistosoma mansoni Infection Intensity and Nutritional Status and Anemia Among Preschool-aged Children in Uganda.

In a cross-sectional analysis of 354 Ugandan children (age 12-48 months) infected with Schistosoma mansoni, we assessed relationships between infection intensity and nutritional morbidities. Higher intensity was associated with an increased risk for anemia (RR = 1.05, 95% confidence interval [CI] 1.01-1.10) yet not associated with risk for underweight, stunting, or wasting.

Preschoolers' deception related to prefrontal cortex activation: An fNIRS study.

Deception is an essential part of children's moral development. Previous developmental studies have shown that children start to deceive at the age of 3 years, and as age increased to 5 years, almost all children were able to deceive for their own benefit. Although behavioral studies have indicated that the emergence and development of deception are related to cognitive abilities, their neural correlates remain poorly understood. Therefore, the present study examined the neural correlates underlying deception in preschool-aged children (N = 89, 44 % boys, age 3.13 to 5.96 years, Han Chinese) using functional near-infrared spectroscopy. A modified hide-and-seek paradigm was applied to elicit deceptive and truth-telling behaviors. The results showed that activation of bilateral dorsolateral prefrontal cortex was positively associated with the tendency to deceive an opponent in a competitive game in the 3-year-olds. In addition, 3-year-olds who showed a high tendency to deceive showed the same brain activation in the frontopolar area as 5-year-olds did when engaged in deception, whereas no such effect was found in 3-year-olds who never engaged in deception. These findings underscore the link between preschoolers' deception and prefrontal cortex function.

Single-cell sequencing of the vermiform appendix during development identifies transcriptional relationships with appendicitis in preschool children.

BACKGROUND: The development of the human vermiform appendix at the cellular level, as well as its function, is not well understood. Appendicitis in preschool children, although uncommon, is associated with a high perforation rate and increased morbidity. METHODS: We performed single-cell RNA sequencing (scRNA-seq) on the human appendix during fetal and pediatric stages as well as preschool-age inflammatory appendices. Transcriptional features of each cell compartment were discussed in the developing appendix. Cellular interactions and differentiation trajectories were also investigated. We compared scRNA-seq profiles from preschool appendicitis to those of matched healthy controls to reveal disease-associated changes. Bulk transcriptomic data, immunohistochemistry, and real-time quantitative PCR were used to validate the findings. RESULTS: Our analysis identified 76 cell types in total and described the cellular atlas of the developing appendix. We discovered the potential role of the BMP signaling pathway in appendiceal epithelium development and identified HOXC8 and PITX2 as the specific regulons of appendix goblet cells. Higher pericyte coverage, endothelial angiogenesis, and goblet mucus scores together with lower epithelial and endothelial tight junction scores were found in the preschool appendix, which possibly contribute to the clinical features of preschool appendicitis. Preschool appendicitis scRNA-seq profiles revealed that the interleukin-17 signaling pathway may participate in the inflammation process. CONCLUSIONS: Our study provides new insights into the development of the appendix and deepens the understanding of appendicitis in preschool children.

Role of epithelial barrier function in inducing type 2 immunity following early-life viral infection.

BACKGROUND: Preschool wheeze attacks triggered by recurrent viral infections, including respiratory syncytial virus (RSV), are associated with an increased risk of childhood asthma. However, mechanisms that lead to asthma following early-life viral wheezing remain uncertain. METHODS: To investigate a causal relationship between early-life RSV infections and onset of type 2 immunity, we developed a neonatal murine model of recurrent RSV infection, in vivo and in silico, and evaluated the dynamical changes of altered airway barrier function and downstream immune responses, including eosinophilia, mucus secretion and type 2 immunity. RESULTS: RSV infection of neonatal BALB/c mice at 5 and 15 days of age induced robust airway eosinophilia, increased pulmonary CD4+ IL-13+ and CD4+ IL-5+ cells, elevated levels of IL-13 and IL-5 and increased airway mucus at 20 days of age. Increased bronchoalveolar lavage albumin levels, suggesting epithelial barrier damage, were present and persisted following the second RSV infection. Computational in silico simulations demonstrated that recurrent RSV infection resulted in severe damage of the airway barrier (epithelium), triggering the onset of type 2 immunity. The in silico results also demonstrated that recurrent infection is not always necessary for the development of type 2 immunity, which could also be triggered with single infection of high viral load or when the epithelial barrier repair is compromised. CONCLUSIONS: The neonatal murine model demonstrated that recurrent RSV infection in early life alters airway barrier function and promotes type 2 immunity. A causal relationship between airway barrier function and type 2 immunity was suggested using in silico model simulations.

Preschool Mathematics and Literacy Skills and Educational Attainment in Adolescents Born Preterm and Full Term.

OBJECTIVES: To test whether preschool academic skills were associated with educational attainment in adolescence and whether associations differed between individuals born preterm and at full term. STUDY DESIGN: This prospective cohort study comprised 6924 individuals, including n = 444 (6.4%) adolescents born preterm (<37 weeks of gestation) from the Avon Longitudinal Study of Parents and Children. Preschool academic (mathematics and literacy) skills were rated by teachers at 4-5 years. Educational attainment at 16 years was informed by attaining a General Certificate of Secondary Education (GCSE) in key subjects mathematics and English. Logistic regressions assessed the association between preterm birth, preschool mathematics, and GCSE Mathematics and between preterm birth, preschool literacy, and GCSE English. RESULTS: Similar numbers of adolescents born preterm and at term achieved a GCSE in mathematics and English (53.6 % vs 57.4% and 59.5% vs 63.9%, respectively; P values > .05). Higher preschool academic skill scores in mathematics were associated with greater odds of attaining GCSE Mathematics and preschool literacy skills were associated with GCSE English. Adolescents born preterm with higher preschool mathematics (OR: 1.51, CI: 1.14, 2.00) and literacy skills (OR: 1.57, CI: 1.10, 2.25) were more likely to attain GCSEs in the respective subject than their term-born counterparts with equal levels of preschool skills. CONCLUSIONS: Preschool academic skills in mathematics and literacy are associated with educational attainment of preterm and term-born individuals in adolescence. Children born prematurely may benefit more from preschool mathematics and literacy skills for academic and educational success into adolescence than term-born individuals.

Housing Characteristics and Hospital Admissions due to Falls on Stairs: A National Birth Cohort Study.

OBJECTIVE: To assess associations between housing characteristics and risk of hospital admissions related to falls on/from stairs in children, to help inform prevention measures. STUDY DESIGN: An existing dataset of birth records linked to hospital admissions up to age 5 for a cohort of 3 925 737 children born in England between 2008 and 2014, was linked to postcode-level housing data from Energy Performance Certificates. Association between housing construction age, tenure (eg, owner occupied), and built form and risk of stair fall-related hospital admissions was estimated using Poisson regression. We stratified by age (<1 and 1-4 years), and adjusted for geographic region, Index of Multiple Deprivation, and maternal age. RESULTS: The incidence was higher in both age strata for children in neighborhoods with homes built before 1900 compared with homes built in 2003 or later (incidence rate ratio [IRR], 1.40; 95% CI, 1.10-1.77 [age <1 year], 1.20; 95% CI, 1.05-1.36 [age 1-4 years]). For those aged 1-4 years, the incidence was higher for those in neighborhoods with housing built between 1900 and 1929, compared with 2003 or later (IRR, 1.26; 95% CI, 1.13-1.41), or with predominantly social-rented homes compared with owner occupied (IRR, 1.21; 95% CI, 1.13-1.29). Neighborhoods with predominantly houses compared with flats had higher incidence (IRR, 1.24; 95% CI, 1.08-1.42 [<1 year] and IRR 1.16; 95% CI, 1.08-1.25 [1-4 years]). CONCLUSIONS: Changes in building regulations may explain the lower fall incidence in newer homes compared with older homes. Fall prevention campaigns should consider targeting neighborhoods with older or social-rented housing. Future analyses would benefit from data linkage to individual homes, as opposed to local area level.

Association of Vitamin A and D Deficiencies with Infectious Outcomes in Children Undergoing Intensive Induction Therapy for Acute Lymphoblastic Leukemia.

OBJECTIVE: To evaluate the association between deficiency of vitamin A or D at diagnosis of pediatric acute lymphoblastic leukemia (ALL) and subsequent infectious complications during induction therapy. STUDY DESIGN: We conducted an institutional review board-approved, retrospective cohort study of children with newly diagnosed ALL from 2007 to 2017 at St. Jude Children's Research Hospital. We measured vitamin D, vitamin D binding protein, retinol binding protein as a surrogate for vitamin A, and immunoglobulin isotypes in serum obtained at ALL diagnosis, and we assessed the association between vitamin deficiencies or levels and infection-related complications during the 6-week induction phase using Cox regression models. RESULTS: Among 378 evaluable participants, vitamin A and D deficiencies were common (43% and 17%, respectively). Vitamin D deficiency was associated with higher risks of febrile neutropenia (adjusted hazard ratio [aHR], 1.7; P = .0072), clinically documented infection (aHR, 1.73; P = .025), and likely bacterial infection (aHR, 1.86; P = .008). Conversely, vitamin A deficiency was associated solely with a lower risk of sepsis (aHR, 0.19; P = .027). CONCLUSIONS: In this retrospective study, vitamin D deficiency was associated with an increased risk of common infection-related complications during induction therapy for ALL. Additional studies are warranted to evaluate whether vitamin D supplementation could mitigate this effect.

Rhinovirus characteristics associated with viremia in childhood asthma.

Although rhinoviruses play a major role in exacerbations of childhood asthma, the presence of rhinovirus (RV) RNA in plasma, referred to as viremia, has been investigated in a few studies. The aim of the study was to investigate the presence of rhinovirus viremia at the time of asthma exacerbation and to describe the molecular characteristics of rhinoviruses associated with viremia. We conducted an observational, prospective, multicenter study in eight pediatric hospitals (VIRASTHMA2). Preschool-aged recurrent wheezers (1-5 years) hospitalized for a severe exacerbation were included. Reverse-transcription polymerase chain reaction (RT-PCR) and molecular typing for RV/enteroviruses (EV) were performed on nasal swabs and plasma. Plasma specimens were available for 105 children with positive RT-PCR for RV/EV in respiratory specimens. Thirty-six (34.3%) had positive viremia. In plasma, 28 (82.4%) of the typable specimens were RV-C, five (14.7%) were EV-D68, and one was RV-A (2.9%). In all cases, the RV/EV type was identical in the plasma and respiratory specimens. In conclusion, RV/EV viremia is frequent in severe exacerbations of preschool recurrent wheezers, particularly in RV-C infections.

Intra-breath changes in respiratory mechanics are sensitive to history of respiratory illness in preschool children: the SEPAGES cohort.

BACKGROUND: Intra-breath oscillometry has been proposed as a sensitive means of detecting airway obstruction in young children. We aimed to assess the impact of early life wheezing and lower respiratory tract illness on lung function, using both standard and intra-breath oscillometry in 3 year old children. METHODS: History of doctor-diagnosed asthma, wheezing, bronchiolitis and bronchitis and hospitalisation for respiratory problems were assessed by questionnaires in 384 population-based children. Association of respiratory history with standard and intra-breath oscillometry parameters, including resistance at 7 Hz (R7), frequency-dependence of resistance (R7 - 19), reactance at 7 Hz (X7), area of the reactance curve (AX), end-inspiratory and end-expiratory R (ReI, ReE) and X (XeI, XeE), and volume-dependence of resistance (ΔR = ReE-ReI) was estimated by linear regression adjusted on confounders. RESULTS: Among the 320 children who accepted the oscillometry test, 281 (88%) performed 3 technically acceptable and reproducible standard oscillometry measurements and 251 children also performed one intra-breath oscillometry measurement. Asthma was associated with higher ReI, ReE, ΔR and R7 and wheezing was associated with higher ΔR. Bronchiolitis was associated with higher R7 and AX and lower XeI and bronchitis with higher ReI. No statistically significant association was observed for hospitalisation. CONCLUSIONS: Our findings confirm the good success rate of oscillometry in 3-year-old children and indicate an association between a history of early-life wheezing and lower respiratory tract illness and lower lung function as assessed by both standard and intra-breath oscillometry. Our study supports the relevance of using intra-breath oscillometry parameters as sensitive outcome measures in preschool children in epidemiological cohorts.

Asthma development is associated with low mucosal IL-10 during viral infections in early life.

BACKGROUND: Viral infection is a common trigger of severe respiratory illnesses in early life and a risk factor for later asthma development. The mechanism leading to asthma could involve an aberrant airway immune response to viral infections, but this has rarely been studied in a human setting. OBJECTIVES: To investigate in situ virus-specific differences in upper airway immune mediator levels during viral episodes of respiratory illnesses and the association with later asthma. METHODS: We included 493 episodes of acute respiratory illnesses in 277 children aged 0-3 years from the COPSAC2010 mother-child cohort. Levels of 18 different immune mediators were assessed in nasal epithelial lining fluid using high-sensitivity MesoScale Discovery kits and compared between children with and without viral PCR-identification in nasopharyngeal samples. Finally, we investigated whether the virus-specific immune response was associated with asthma by age 6 years. RESULTS: Viral detection were associated with upregulation of several Type 1 and regulatory immune mediators, including IFN-É£, TNF-α, CCL4, CXCL10 and IL-10 and downregulation of Type 2 and Type 17 immune mediators, including CCL13, and CXCL8 (FDR <0.05). Children developing asthma had decreased levels of IL-10 (FDR <0.05) during viral episodes compared to children not developing asthma. CONCLUSION: We described the airway immune mediator profile during viral respiratory illnesses in early life and showed that children developing asthma by age 6 years have a reduced regulatory (IL-10) immune mediator level. This provides insight into the interplay between early-life viral infections, airway immunity and asthma development.

Effect of a Center-Based Early Childhood Care and Education Program on Child Nutritional Status: A Secondary Analysis of a Stepped-Wedge Cluster Randomized Controlled Trial in Rural Sindh, Pakistan.

BACKGROUND: High-quality early childhood care and education (ECCE) programs can positively impact children's development. However, as an unintended consequence, ECCE attendance may also affect children's nutritional status. OBJECTIVE: We evaluated the effect of a center-based ECCE intervention on child nutritional outcomes in rural Pakistan. METHODS: This study utilized data from a stepped-wedge cluster randomized controlled trial of a center-based ECCE program that trained female youth to run high-quality preschools for children aged 3.5-5.5 y (Youth Leaders for Early Childhood Assuring Children are Prepared for School (LEAPS) program) in rural Sindh, Pakistan. The program did not include any school meals. A total of 99 village clusters were randomized to receive the LEAPS intervention in 3 steps, and repeated cross-sectional surveys were conducted to assess the impact on children (age: 4.5-5.5 y) at 4- time points. ITT analyses with multilevel mixed-effect models were used to estimate the effect of the intervention on child anthropometric outcomes. RESULTS: The analysis included 3858 children with anthropometric data from 4 cross-sectional survey rounds. The LEAPS intervention was found to have a positive effect on child height-for-age z score (mean difference: 0.13 z-scores; 95% confidence interval [CI]: 0.02, 0.24). However, there was a negative effect on weight-based anthropometric indicators, -0.29 weight-for-height z score (WHZ) (95% CI: -0.42, -0.15), -0.13 BMI z score (BMIZ) (95% CI: -0.23, -0.03), and -0.16 mid-upper arm circumference-for-age z score MUACZ (95% CI: -0.25, -0.05). An exploratory analysis suggested that the magnitude of the negative effect of LEAPS on WHZ, BMIZ, and weight-for-age z score (WAZ) was greater in the survey round during the COVID-19 lockdown. DISCUSSION: The LEAPS intervention positively affected child linear growth but had negative effects on multiple weight-based anthropometric measures. ECCE programs in low- and middle-income country settings should evaluate the integration of nutrition-specific interventions (eg school lunch, counseling on healthy diets) and infection control strategies to promote children's healthy growth and development. CLINICAL TRIAL REGISTRY: clinicaltrials.gov, NCT03764436, https://clinicaltrials.gov/ct2/show/NCT03764436.

Evidence for Criterion-Related Validity of Pressure-Mediated Reflection Spectroscopy for Approximating Fruit and Vegetable Consumption among Preschool Children.

BACKGROUND: Skin carotenoids are a valid biomarker for approximating fruit and vegetable consumption (FVC). Veggie Meter® (VM®, Longevity Link Corp.) is a pressure-mediated reflection spectroscopy (RS)-based device that allows for noninvasive and rapid assessment of skin-carotenoid score (SCS) in adults and children. Although VM® is established as a valid tool to measure FVC in adults, there is limited research supporting the validity evidence of the VM® to approximate FVC among preschool children. OBJECTIVE: The current study aims to assess evidence supporting the criterion-related validity of RS-based SCS for approximating FVC among preschool children (3-5-y old). METHODS: We collected cross-sectional data from typically developing preschool children (n = 136) attending the Child and Adult Care Food Program-participating family child care home settings (FCCHs) (n = 46) in Nebraska. Research team members collected children's height and weight to calculate body mass index; and measured children's SCS using the VM®. Children's FVC in FCCHs were collected using dietary observation. In addition, parents (n = 89) completed a shortened food frequency questionnaire to report children's FVC at home. Kendall's Tau (τ) correlation tests were conducted to measure the association between children's SCS with FVC in FCCHs and with parent-reported total fruit and vegetable (FV) frequency scores. RESULTS: Children's SCS were significantly correlated with their mean FVC in FCCHs, τ = 0.14 (P = 0.02), total provitamin A carotenoids intake in FCCHs, τ = 0.19 (P < 0.001), and with parent-reported total FV frequency score, τ = 0.16 (P = 0.04). CONCLUSION: The correlation coefficients in this study are comparable with results from a meta-analysis examining associations between FVC and SCS in 7-10-y-old children (r = 0.20). Thus, evidence suggests that RS offers a potentially valid, objective, and feasible method to assess preschool children's total FVC in multiple settings, especially in conjunction with other dietary assessment tools.

Longitudinal Growth Trajectories in Children with Cow's Milk Allergy: Effects of Elimination Diet and Post-Termination Period.

INTRODUCTION: The primary dietary approach for managing cow's milk allergy (CMA) is the elimination diet. We aimed to compare the growth patterns of children with CMA during and after the elimination diet with healthy peers and identify influencing factors. METHODS: We compared 74 CMA children with age-matched healthy peers. Anthropometric data were collected during the third month of cow's milk elimination (CME) diet (T1), 3 months after diet cessation (T2), and after ≥3 months of normal diet (T3). Control group measurements coincided. Nutrient intake was assessed by a 3-day record, and patient laboratory results were noted at T3. RESULTS: CMA children had consistently lower weight-for-age (WFA) and height-for-age (HFA) z-scores than controls. WtHt z-score of patients was lower than those of the healthy group at T2. HC z-scores of patients were lower than those of the healthy group at T0, T2, and T3. At T3, the HFA z-score of the CME group demonstrated a negative correlation with the duration of the elimination diet (p = 0.045). Inadequate intake of energy, vitamins A, E, B1, B6, C, folic acid, magnesium, and iron was significantly higher in CMA children (p < 0.05). T3 WFA z-score correlated positively with fiber, vitamin B1, magnesium, and iron intake (p < 0.05). T3 WtHt showed a positive moderate correlation with energy, protein, vitamin E, vitamin B1, vitamin B2, vitamin B6, calcium, magnesium, phosphor, iron intake (p < 0.05). CONCLUSIONS: Post-elimination diet, children with CMA need sustained monitoring and potentially micronutrient supplementation to match healthy peers' growth.

Are salivary NO2- / NO2- and NO3- levels biomarkers for dental caries in children? Systematic review and meta-analysis.

The literature is conflicting regarding salivary nitrite (NO2-)/nitrite and nitrate (NO2- and NO3-) levels in children affected by dental caries. For this reason, a systematic review to provide a consensus on the subject was propose, whose objective is to verify whether these molecules could be used as biomarkers in children with caries. A comprehensive search was performed on online database and eleven articles were included in the meta-analysis. The methodological quality of studies was assessed by Newcastle-Ottawa Scale recommended for case-control studies and by AXIS tool for cross-sectional studies. Grading of Recommendations Assessment, Development and Evaluation was used for the assessment of the certainty of the evidence for each outcome. The results showed lower NO2- levels in the group of children affected by dental caries (SMD = -2.18 [-3.24, -1.13], p < 0.01). Age, saliva collection and methods of evaluation can impact the results. When evaluating the severity of the condition, an important variation was detected in relation to the different evaluation methods NO2-/NO2- and NO3-. In conclusion, based on the evidence presented, the results suggest that NO2- levels in saliva are a possible biomarker of dental caries. Results should be evaluated with caution due to the very low evidence from primary studies. Longitudinal studies are necessary to strengthen this hypothesis.

Editorial: Reciprocity between sleep and mood in early childhood - an under-explored neural marker of depression risk.

We emphasize the potential importance of the role of early alterations in sleep and circadian rhythms as a biological marker of early-onset depression in the preschool period. This builds on findings of the reciprocal relationship between sleep and mood as well as the validity of preschool depression well established in the extant literature. This editorial highlights two recent studies published in JCPP in 2024 defining the duration of clinically impairing depressive symptoms in young children and methods that are now feasible to track daily patterns of sleep and circadian rhythms and show their relation to mood. We propose future studies to investigate these relationships in young children at risk for depression.

Behavioral characteristics of toddlers later identified with an autism diagnosis, ADHD symptoms, or combined autism and ADHD symptoms.

BACKGROUND: Autism commonly co-occurs with attention-deficit/hyperactivity disorder (ADHD), but less is known regarding how ADHD symptoms impact the early presentation of autism. This study examined early behavioral characteristics of a community sample of toddlers later identified with autism diagnosis, ADHD symptoms, combined autism and ADHD symptoms, or neither condition. METHODS: Participants were 506 toddlers who were part of a longitudinal study of children's behavioral development. Parents completed questionnaires about their children's behavior at two time points. Four groups were identified based on study measures or medical record: autism diagnosis (n = 45), elevated ADHD symptoms (n = 70), autism and ADHD symptoms (n = 30), or neurotypical development (n = 361). Relationships between early parent report of autism- and ADHD-related behaviors, social-emotional and behavioral functioning, and caregiver experience and subsequent group designation were evaluated with adjusted linear regression models controlling for sex. RESULTS: Significant group differences were found in measures of autism-related behaviors, ADHD-related behaviors, externalizing and internalizing behaviors, and parent support needs (p < .0001). Pairwise comparisons indicated toddlers later identified with combined autism diagnosis and ADHD symptoms had higher levels of autism-related behaviors, externalizing and internalizing behaviors, and autism-related parent support needs compared to the other groups. Toddlers with subsequent elevated ADHD symptoms or combined autism diagnosis and ADHD symptoms exhibited similar levels of ADHD-related behaviors, while both groups displayed more ADHD-related behaviors than toddlers subsequently identified with autism or those with neither condition. CONCLUSIONS: In this community sample, toddlers for whom combined autism diagnosis and ADHD symptoms were subsequently identified showed a distinct presentation characterized by higher early autism-related behaviors, broader behavioral concerns, and higher parent support needs. Presence of ADHD symptoms (alone or in combination with autism) was associated with higher parent-reported ADHD-related behaviors during toddlerhood. Results indicate that ADHD-related behaviors are manifest by toddlerhood, supporting screening for both autism and ADHD during early childhood.

Editorial: Are government early years learning and development frameworks evidence-based? A scientist's perspective.

Not all young children attend nurseries, childminders or other group settings before they start school, but many do. It is common for countries to set out a framework to guide practice for early years providers (such as nurseries) to follow. The conundrum regarding these frameworks for young children is that proving evidence of a causal link between early environments and later outcomes is very challenging scientifically. So how do governments choose what learning and development practices and goals to make mandatory for childcare providers? And is it realistic to expect early years providers to meet the legal requirements that these frameworks impose? We do not know which learning and development practices impact positively on later outcomes, and we certainly do not know if there is a one-size-fits-all approach for an early years framework that is guaranteed to work.

Oral language enrichment in preschool improves children's language skills: a cluster randomised controlled trial.

BACKGROUND: Oral language skills provide the foundation for formal education, yet many children enter school with language weaknesses. This study evaluated the efficacy of a new language enrichment programme, the Nuffield Early Language Intervention-Preschool (NELI Preschool), delivered to children in the year before they enter formal education. METHODS: We conducted a preregistered cluster randomised controlled trial in 65 nursery schools in England (https://doi.org/10.1186/ISRCTN29838552). NELI Preschool consists of a 20-week whole-class language enrichment programme delivered by a teacher each day for 20 min. In addition, children with the weakest language skills in each class are allocated to receive additional targeted support delivered by classroom assistants (whole-class + targeted). The language skills of all children (n = 1,586) in participating classrooms were assessed using the LanguageScreen automated app (https://oxedandassessment.com/languagescreen/). Settings were then randomly allocated to an intervention or control group. The children with the weakest language in each class (whole-class + targeted children n = 438), along with four randomly selected children in each class allocated to the whole-class only programme (n = 288) were individually tested on a range of language measures. RESULTS: Children receiving NELI Preschool made larger gains than children in the control group on an oral language latent variable (whole-class children d = .26; whole-class + targeted children d = .16). CONCLUSIONS: This study provides good evidence that whole-class intervention delivered in preschool can produce educationally significant improvements in children's language skills. The intervention is scaleable and relatively low cost. These findings have important implications for educational and social policy.