ABSTRACTAnxious temperament (AT) is a nonhuman primate phenotype that models childhood behavioral inhibition, a prominent risk factor for anxiety disorders and stress‐related psychopathology. To understand its earliest antecedents, we characterized AT's developmental trajectory over the first year of life. Infant monkeys (n = 35, 24 females) were longitudinally phenotyped for AT by assessing threat‐related increases in freezing behavior, reductions in coo‐calling, and increases in circulating cortisol at 1.5, 6, 12, 24, and 52 weeks. AT levels increased linearly, reaching mature levels by 52 weeks. Individual differences in AT, and its components, were stable across development. These findings support further studies during early primate life aimed to uncover neurobiological factors mediating development of this phenotype, which in humans is linked to stress‐related psychopathology.SummaryAnxious temperament (AT) or behavioral inhibition (BI), a trait‐like characteristic in humans associated with later development of anxiety‐related psychopathology, is evident during earliest weeks of primate life.Developmental patterns of AT and its components (threat‐related freezing, reductions in cooing, increases in plasma cortisol) across the first year of primate life are presented.Individual differences in AT and its behavioral and hormonal components are relatively stable across the first year of life, reaching maturity by one year.

Food allergies affect 4%-6% of the pediatric population and are often present within the first 2 years of life. Cord blood cells and cytokines in high-risk infants can predict allergic problems; however, their predictive value remains unclear. This study aimed to determine whether a cow's milk allergy in infants can be predicted using a basophil activation test (BAT) of cord blood samples by stimulating basophils with milk protein antigens (cow's milk and casein). We collected cord blood during the birth of 30 mother-child pairs and immediately analyzed BAT stimulated with milk protein antigens. One year later, we compared the results of those infants who developed an allergy to those who did not. We found that infants with a casein-BAT value ≥2.6 were 33.2 times more likely than those with a casein- BAT value <2.6 to develop food allergy symptoms within the first year of life (P=0.03). High casein-BAT values in cord blood may predict the development of food allergies during the first year of life. Although no association with cow's milk sensitivity has been found, casein sensitivity may indicate food allergy risk. However, further studies are required to confirm this association.

This study examined the experiences of infants diagnosed with fragile X syndrome (FXS) in the newborn period and their caregivers during the infant's first year of life. The primary objective was to understand caregiver concerns and access to early intervention services for infants diagnosed with FXS presymptomatically. Participants for this study were part of a pilot intervention programme for newborns with FXS and their caregivers. A mixed-methods approach was taken combining data from caregiver questionnaires as well as intervention session notes to identify caregiver concerns and early intervention services. Caregivers of infants with FXS consistently reported concerns in motor development in the first few months of life with increasing concern regarding communication development closer to 12 months of age. Despite all being eligible based on having an established condition and instruction for accessing early intervention services provided by the intervention team, only half of participants were enrolled in their state's Part C programme by the child's first birthday. Occupational therapy was the most accessed service (33% of infants), followed by physical therapy (27%), feeding therapy (20%), speech therapy (13%) and developmental play therapy (7%). Although one of the main benefits of earlier diagnosis is purported to be earlier access to interventions, we found infants diagnosed with FXS prior to emergence of symptoms experienced barriers to accessing early intervention services, despite FXS being an established condition for Part C services. These findings highlight the need for further exploration of the referral process for infants diagnosed with neurogenetic conditions in infancy.

Factors influencing the early-life skin microbiome, and the association with atopic dermatitis (AD), are relatively unexplored. To evaluate associations with the infant skin microbiome during the first year of life. 3-month-old infants from the Enquiring About Tolerance (EAT) birth cohort were examined for AD at enrolment, 1 and 3 years of age. Parent-completed questionnaires, trans-epidermal water loss (TEWL), and filaggrin mutation status were evaluated. Bacterial swabs were collected from the elbow crease and volar forearm in 148 infants at 3 months and 1 year of age, and the microbiome composition was characterized using 16S rRNA gene sequencing (V3-V4 region). Shannon diversity was significantly higher at the forearm compared to the elbow. Staphylococcus, Acinetobacter, and Streptococcus were the most abundant genera across time and body-site. Microbiome community composition was primarily associated with body-site and age (p≤0.001, both). Other significant associations were found with ethnicity (p=0.009), filaggrin status (p≤0.001), urban-vs-rural residence (p=0.005), older siblings (p=0.041), bath product usage at 3 months (p=0.011), but not with pets (p=0.159), systemic antibiotics (p=0.27) nor with bathing frequency (p=0.109). The microbiome was associated with elevated TEWL (3-months p=0.004, 1-year p≤0.001) and with concurrent AD (3-months p=0.027, 1-year p≤0.001). Streptococcus parasanguinis was significantly less abundant in non-lesional skin of infants with AD at 3 months. In addition to age and body-site, the infant skin microbiome is associated with heritable factors, the home environment, hygiene practices, and with the presence of AD.

ABSTRACTObjectiveTo describe the clinical and demographic profile of Australian children first diagnosed with acute rheumatic fever (ARF) or rheumatic heart disease (RHD) before the age of 5 years, with comparison to children aged 5–14 years.MethodsLinked emergency department, hospitalisation, RHD register and death records from the End RHD in Australia: Study of Epidemiology were used to identify first ARF/RHD diagnosis occurring in < 15‐year‐olds. Demographic/clinical profiles and pre‐diagnosis healthcare interactions were analysed with stratification into 5‐year age groups.DesignRetrospective cross‐sectional linked administrative data analysis.SettingNorthern Territory, South Australia, Queensland and Western Australia.ParticipantsChildren aged < 15 years at first hospitalisation or notification for ARF or RHD, 2001–2017.Main Outcome MeasuresDisease stage and severity at diagnosis, register notification status, clinical history prior to ARF or RHD diagnosis.ResultsOf 2382 children diagnosed with ARF/RHD aged < 15 years, 180 (7.6%) were aged under 5 years. Among under 5‐year‐olds with ARF or RHD, 30.6% had not been notified to RHD registers. A total 49 under 5‐year‐olds were diagnosed with RHD; with 22 (44.9%) classified as having mild disease, 16 (32.7%) moderate and 6 (12.2%) severe. High hospitalisation rates for injury in the first year of life were observed for the < 5‐year‐old cohort with ARF/RHD.ConclusionsWe present the first comprehensive Australian evidence that ARF and RHD diagnoses are occurring in Australian children aged under 5 years. Greater awareness among clinicians is needed regarding ARF/RHD as a potential diagnosis in this young, high risk age group.

Fine and ultrafine particulate matter components and autism spectrum disorder (ASD).

Respiratory syncytial virus (RSV) infects nearly all children by age 2 to 3 years, and early-life infection-defined using active and passive surveillance with quantitative polymerase chain reaction- and serology-identified infection-has been implicated as a causal factor in childhood asthma. As such, identifying infants that are likely to be infected with RSV during this critical susceptibility window has important implications for identifying individuals at risk for chronic respiratory sequelae. However, determining the age of RSV infection in large populations is challenging because many infections are asymptomatic, making accurate detection dependent on intensive and costly surveillance. To address this, we developed a probability model for age of first RSV infection. It uses an infant's birthdate, demographic covariates, and publicly available RSV circulation data to determine the probability they were first infected at any age from birth to one year. Our model is interpretable, accounts for nearly 37% of the variance in age at first infection, and generalizes across four independent datasets collected from participants in the United States, where we use it to accurately predict age of first infection in two independent cohorts. Our work facilitates reliable estimation of the age of infant RSV infection during the first year of life without the need for active surveillance.

BackgroundThe use of biologic therapies among women of reproductive age has significantly increased, with accumulating evidence supporting their safety during pregnancy. Nevertheless, the long-term implications for the infant's developing immune system remain inadequately understood. This study investigated the association between antenatal exposure to biologic agents and the risk of infections in infants during their first year of life.MethodsThis nationwide cohort study included all women insured by Clalit HMO who delivered between January 2012 and October 2023. Infants exposed to biologic agents during the second or third trimester were compared to those with no exposure. Propensity score analysis adjusted for maternal chronic medical conditions, pregnancy and delivery characteristics, vaccination status, and timing of birth. Cox regression modeling evaluated the dynamic effects of biologic exposure post-delivery. Infection events were identified using ICD-10 codes. Vaccination adherence was assessed by the total number of vaccine doses administered.ResultsOf 297,480 live births, 395 infants were exposed to biologic therapies antenatally. Infection rates were not significantly higher in infants exposed to biologics compared with unexposed infants (propensity-adjusted odds ratio [OR]: 1.11; 95% CI: 0.66–1.89; p = 0.7) (Figure A). Cox regression analysis similarly showed no significant increase in the hazard of infections (hazard ratio: 1.04; 95% CI: 0.90–1.20; p = 0.6) (Figure B). Antibiotic consumption and hospitalization rates did not differ significantly between exposed and unexposed infants (OR for antibiotic consumption: 1.22; 95% CI: 0.93–1.62; p = 0.2; OR for hospitalization: 1.09; 95% CI: 0.49–2.44; p = 0.8). Vaccination adherence was lower for the live-attenuated rotavirus vaccine among biologic-exposed infants (p < 0.001), whereas adherence to pneumococcal vaccination was comparable between groups.ConclusionInfants exposed to maternal biologic therapy during the second or third trimester of pregnancy did not have an increased risk of infections in the first year of life. However, biologic-exposed infants had significantly lower adherence to the live-attenuated rotavirus vaccine compared to unexposed infants.DisclosuresDavid Greenberg, Professor MD, GSK: Advisor/Consultant|GSK: Honoraria|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria Dana Danino, Dr. MD, Pfizer: Grant/Research Support

Targeted gene panel testing in pediatric epilepsy: Diagnostic outcomes and expanding genetic insights.

ABSTRACT Important breakthroughs in understanding the role of attachment for social functioning and wellbeing have always gone hand in hand with the construction of new measurement paradigms. In her 1986 book on five methods of assessment, Mary Main concluded that experiences and representations of attachment shape general, stable, and coherent categories of mental organization. The rules for classifying these categories were derived from data drawn from new, experimentally controlled measures. Taking inspiration from Main’s approach, the current paper argues that a data-driven approach that leverages advances in naturalistic recording and computation may go further and also deliver a detailed understanding of how and when patterns of attachment behavior are formed during the first year of life. This paper describes how tools for long-term, fine-grained, multimodal recording can be embedded in daily family life and combined with high-throughput processing and supervised machine learning. Predictive models of dynamic interactions between features of infants’ and caregivers’ behaviors can be explored and interpreted to arrive at testable theory. By casting theory in the form of agent-based models, we can iteratively rebuild Bowlby’s original conceptualization of behavioral control systems for attachment and caregiving, which provided the starting point of Main’s empirical forays. We describe the theoretical gaps in current attachment research as well as the opportunities for multidisciplinary research that could be addressed by an approach that builds on Main’s abductive logic.

Abstract Introduction and aims Epidermolysis bullosa (EB) is a family of rare, incurable, inherited disorders characterized by extreme skin and mucosal fragility. The two most severe forms are dystrophic EB (DEB), caused by genetic variance in type-VII collagen, and junctional EB (JEB), caused by genetic variance in genes encoding basement membrane proteins laminin 332 (α3, β3, γ2), type XVII collagen or integrin α6β4. Despite clinical similarities, there are dramatic differences in the life expectancies of patients with these subtypes. Patients with RDEB survive to early or midadulthood, comparatively patients with JEB rarely survive beyond the first year of life. We aim to explore the disparity in life expectancy using a transcriptomic and an in vivo approach. Methods We performed bulk RNA sequencing on 7 DEB and 13 JEB samples (3 LAMA3, 8 LAMB3 and 2 LAMC2) to identify molecular and cellular differences underpinning these diseases. Principal component analysis and differential gene expression (DEG) analysis was conducted to explore the relatedness between subtypes. Immunohistochemistry was used to validate these findings in mouse models of EB. Results Three distinct clusters of samples were grouped by condition; one DEB and two JEB clusters separated by LAMA3 and LAMC2 mutations. Pathway and gene ontology (GO) analysis of DEGs indicated an upregulation in cell death, proinflammatory pathways and interleukins (ILs) (IL-1, IL-11, CXCL12 and β-defensins) which stimulate the adaptive immune response. In addition, an abundance of transcriptional factors linked to wound healing (MMP2, COL1A1), collagen remodelling (LOX), fibrosis (TGFβ) and epidermal development (EPPK1, TGM1, FLG and KRT14) were upregulated in patients with JEB compared with those with DEB. These changes have been validated in mouse models of EB at Queen Mary University of London. Conclusions We have identified and validated significant changes between EB subtypes. The use of pathway and GOterm analysis identified altered pathways and molecular drivers that could be used as a novel approach for therapeutic treatments for EB.

From genotype to phenotype in early childhood asthma.

Early adversity is associated with brain changes that negatively impact development, social-emotional functioning, and academic achievement. The multifaceted nature of adversity complicates efforts to isolate specific factors that affect brain development and developmental outcomes. In the present study, we leverage parent survey data and longitudinal electroencephalography (EEG) data collected from infants during 4-, 9-, and 12-mo well-child visits at a large hospital-based urban primary care clinic serving predominantly low-income families (293 infants, 667 EEGs). Using a network framework, we aimed to identify specific socioeconomic and psychological factors associated with differences in infant brain development. We find that mothers who report to be income insufficient were more likely to have lower educational attainment, report low-income, experience higher levels of stress, and encounter more adverse life events. Controlling for these variables, income insufficiency was specifically associated with delayed brain development in the first year of life; infants developing in a household where parents felt their income was inadequate to support the family's needs exhibited slower rates of change in alpha peak frequency, alpha power, and beta power. Together, these findings provide a framework of understanding and visualizing how early adversity impacts neurodevelopment and provides evidence for the potential utility of maternal income sufficiency as an additional screening tool to accelerate identification of populations most vulnerable and in need for early intervention.

Inherited retinal diseases (IRDs) are among the most common causes of visual impairment in children and young adults. The aim of our study was to characterize early clinical manifestations, main IRDs and causative genes and in a pediatric cohort. Retrospective study case series of children with a diagnosed IRD. Data extracted from medical charts included IRD type, clinical manifestations, demographic details and molecular analysis when available. We have identified 199 children. The earliest and most common symptom was nystagmus (mean age: 1.78 years), followed by photophobia, strabismus and high refractive errors. The most common diagnoses were retinitis pigmentosa (RP), achromatopsia and CSNB; achromatopsia and Leber's congenital amaurosis presented significantly earlier than other IRDs. Most common identified genes were CNGA3, TRPM1, CNGB3 and CRB1. Nystagmus was the earliest and most common symptom, particularly if disease manifests during the first year of life. Photophobia, strabismus and high refractive errors were also common. Main IRDs in our studied population were RP, achromatopsia and CSNB, and the most common genes identified were CNGA3 and TRPM1, differing from the ones seen later in adulthood.Identification of IRDs early clinical manifestations can help affected families reach early diagnosis, support and family planning.

ABSTRACTStaphylococcus epidermidis is widely found throughout the entire length of human skin and animals since the first year of life, providing a natural protective barrier against other pathogenic microorganisms. Therefore, related to its reputation, it is of utmost importance to investigate the virulence capacity for strains of this species. The aim of this study was to evaluate the safety of S. epidermidis ST0409KOC, a strain isolated from Bulgarian feta‐type cheese, and to explore its bacteriocinogenic property against different strains of Listeria monocytogenes and other pathogens. S. epidermidis ST0409KOC can be considered a safe strain regarding its virulence genetic background, presenting only a virulence gene of IS257 among the 18 genes investigated. Moreover, it showed high bacteriocinogenic activity against different serotypes of L. monocytogenes, and its bacteriocin may be of great interest for controlling this pathogen. However, bacteriocin production when associated with pathogenic or opportunistic strains can be considered as a virulence factor, since it will improve survival abilities for the producer. Related to the observed results regarding the safety of the investigated strain, production of bacteriocin, and potential beneficial features, the S. epidermidis ST0409KOC strain is a strong candidate for use as a probiotic in different applications, and further studies are needed.

Childhood obesity disproportionately affects priority populations, including racial and ethnic minority groups and those with lower socio-economic backgrounds. These groups often encounter barriers to accessing public health services and may benefit from targeted interventions. This scoping review aimed to identify the characteristics of populations involved in interventions to prevent early childhood obesity and to understand whether and how existing interventions targeted and reached priority populations. Databases and trial registries were systematically searched until 4 October 2024, for planned, ongoing, and completed randomised controlled trials evaluating parent-focussed, behavioural interventions for childhood obesity prevention, starting within the first year of life. Two reviewers independently extracted data using a customised tool. Of the 11 960 articles identified, 82 trials were eligible. Most trials (87%) were conducted (or planned) in high-income countries, 11% in upper middle-income countries, and 2% in lower middle-income countries. Priority populations included parent-child dyads from specific ethnic or racial groups facing psychological, social, and/or economic disadvantages. Among the completed trials, 54% targeted priority populations, yet only 33% exclusively enrolled participants from these groups. Additionally, less than a quarter of the trials involved priority populations in the design of interventions (17%) and developed tailored interventions for these groups (21%). Current interventions do not sufficiently target, reach and engage priority populations. To achieve health equity in early childhood obesity prevention, it is essential to include underserved and at-risk populations in research and intervention design.

Clinical and genetic analysis of epilepsy in children with SCN8A gene variants.

to understand how women who received breastfeeding counseling make breastfeeding-related decisions during their children's first year of life. a qualitative study conducted with women who received breastfeeding counseling in rooming-in units of three university hospitals, two located in the Southeast region and one in the Northeast region. Semi-structured interviews were conducted between May and September 2024, assessed using the Symbolic Interactionism and Thematic Analysis frameworks. eleven women participated, highlighting the interactional context of breastfeeding counseling as a promoter of safety and trust, with technical and emotional contributions to overcoming breastfeeding challenges. breastfeeding counseling proved to be a care technology with positive influences on maintaining exclusive breastfeeding in the first year of children's lives.

Neonatal BCG vaccination to prevent respiratory infections in the first 5years of life: results from the MIS BAIR randomised controlled trial.

Compared to adult-directed speech (ADS), infant-directed speech (IDS) is acoustically exaggerated. It has been proposed that such exaggerations facilitate speech sound discrimination and phonetic learning in young infants. This proposal was tested here using an abstract mismatch negativity (MMN) paradigm to assess 4- and 9-month-old infants' and adults' neural responses to a vowel contrast produced in IDS and ADS. In 4-month-olds, IDS stimuli elicited both a negative MMN and a positive mismatch response (MMR), but ADS stimuli elicited only an MMR, which is associated with acoustic change detection, typical for infants of this age who are still acquiring their native language's phonemic inventory. In 9-month-olds and adults, both IDS and ADS stimuli elicited MMN, associated with native phonemic processing. The 9-month-olds also generated an MMR for IDS. These results suggest that for 4-month-olds, for whom speech processing is predominantly acoustic/phonetic, the heightened acoustic variability and phonetic saliency in IDS, compared to ADS, augments vowel discrimination, whereas for 9-month-olds, their additional phonemic processing affords vowel discrimination in both augmented (IDS) and non-augmented (ADS) speech contexts. This neural level evidence is consistent with the perceptual attunement argument that early language-general acoustic/phonetic speech processing gives way to a more abstract form of phonemic speech processing as a function of experience in a specific language environment, and also demonstrates that the properties of IDS may facilitate this developmental transition during infants' first year of life.