Child and Adolescent Health

Wen et al. investigate associations between intestinal disturbances and mortality in children hospitalized with complicated severe malnutrition. Differences are seen in the fecal metabolome of children who die compared with those who are discharged, with integrative analyses suggesting an indirect role for intestinal inflammation in mortality.

Zhong, Danielsson et al. longitudinally profile the serum proteome in a cohort of extremely preterm infants. They identify a postnatal time-dependent stereotypic pattern of development in the blood proteome from premature birth to term-equivalent age.

Zhang, Zhou et al. correlate birth weight and childhood body size with later development of chronic diseases and multimorbidity. Using data from the UK Biobank they show low or high birth weight and a body size in childhood that differs from the average associate with higher risks of developing multimorbidity and many chronic conditions in late life.

Clarke, Evangelista et al. use a knowledge graph (ReproTox-KG) to characterize associations between small molecule compounds and their potential to induce specific birth abnormalities. They identify over 500 birth defect/gene/drug connections that can explain molecular mechanisms for drug-induced birth defects.

Benefits of breastfeeding are well established, but a comprehensive study about its impacts on hospitalizations is lacking. Here, the authors use Korean nationwide birth cohort data (n = 1,608,540) and find that breastfeeding for at least 6 months was associated with a lower risk for subsequent hospital admissions.

Disruption to the brain’s oxygen supply triggers pathological dynamics and brain injuries. Here, the authors develop a model of coupled metabolic-neuronal activity that generates burst suppression patterns similar to those of infants after birth asphyxia.

Environmental exposures in early life can have lasting health effects, but the molecular mechanisms are not well understood. Here, the authors discover >1000 associations between exposure factors and child multi-omics profiles, revealing signatures for diet, toxic chemical compounds, essential trace elements, and weather conditions.

Here, by performing multi-omics microbiome analyses in a cohort of children with new-onset T1D, the authors characterize altered microbial functional and metabolic traits involved in T1D, which they validate in animal experiments, together providing potential avenues for microbiome-based interventions.

Based on preclinical studies, gamma aminobutyric acid (GABA) and immunization for the enzyme that produces GABA glutamate decarboxylase (GAD) could be a potential therapy for type 1 diabetes. Here the authors report that in a placebo-controlled, double blind trial in children with new onset type 1 diabetes oral GABA plus GAD did not preserve beta-cell function measured as fasting/meal-stimulated c-peptide levels.

Chan et al. develop an open-source smartphone-based tympanometer to evaluate middle ear function. The authors test their device in a group of paediatric patients at an audiology clinic and report a high level of agreement in audiologists’ classification of tympanograms produced using this device compared with a commercial device.

Increased droughts are associated with climate change. Here, the authors reveal an association between long-term drought and an elevated risk of diarrhea in children under five in low- and middle income countries, and suggest that improving water quality, sanitation, and hygiene practices might reduce the risk.

Helldén et al. apply the Sustainable Development Goals (SDGs) Synergies approach to investigate interactions between SDGs and child health in Cambodia in an interdisciplinary Cambodian stakeholder group. They identify SDGs that positively influence child health and show that progress on child health also promotes the achievement of most other goals.

Airaksinen et al. describe an infant wearable system that accurately quantifies key aspects of infant motor ability and uses deep learning algorithms to analyze movement signals. Motor ability age and maturation can be predicted, with the predictions correlating with other clinical and parental assessments.

Exposure to synthetic and natural toxicants is a major risk factor in the etiology of disease. Here, authors describe the development of a method to quantify >80 xenobiotics and apply it to assess early-life exposure in vulnerable infants.

Pregnant women have been disproportionately under-vaccinated against COVID-19, partly because they were excluded from initial trials. This systematic review and meta-analysis supports efficacy of vaccination in pregnancy, and finds no evidence of adverse maternal or perinatal outcomes.

Kulvicius, Zhang et al. propose a non-invasive approach to classify infant movements using a pressure sensing device. Applying neural network architectures to pressure sensing data enables large-scale motion data acquisition and analysis.

Economic shocks may lead to food insecurity and therefore acute child malnutrition (wasting). Here, the authors use data from Demographic Health Surveys to estimate impacts of past economic shocks on wasting and project possible effects of shocks related to the COVID-19 pandemic.

Better understanding of the genetic basis of acne can pave the way to more effective treatments. Here, the authors perform a genome-wide association study meta-analysis of >20,000 cases and identify 29 new acne susceptibility loci, uncovering genetic links to Mendelian hair and skin disorders and other complex traits.

Micronutrient supplements are key to global efforts to address child malnutrition. Here, in a cohort of children, previously enrolled into a large cluster randomized controlled trial of micronutrient supplementation in Pakistan, Popovic et al. find that vitamins and iron increase carriage of protozoa and fungi in the gut, potentially disrupting the bacterial microbiome.

India’s national school feeding program is the largest of its kind in the world, but the long-term program benefits on nutrition are unknown. Here, the authors show intergenerational program benefits, in that women who received free meals in primary school have children with improved linear growth.

PREGCARE is a new strategy for families who had a child with a pathogenic de novo mutation, that efficiently identifies couples at higher recurrence risk due to parental mosaicism, while reassuring many others that their recurrence risk is negligible.

The integrator complex is required for the synthesis of protein coding and non-coding RNA and contains the protein INTS13. Here, the authors find germline mutations in INTS13 in two families with oral facial digital syndrome and show that the mutation affects the c-terminal domain of the protein and disrupts cilliogenesis.

Lu, Andescavage et al. scanned fetal brains by MRI and assessed maternal distress before and during the COVID-19 pandemic. Impaired fetal brain growth, delayed cerebral cortical gyrification and increased maternal distress was seen in COVID-19 pandemic era pregnancies.

Nakahara, Michikawa et al determined the physical activity and sleep habits of women before and during pregnancy and compared these with diagnoses of autism spectrum disorder in their offspring. Abnormal sleep and reduced physical activity during pregnancy were associated with a diagnosis of autism spectrum disorder.

The relationship between social media use and well-being might change across adolescent development. Here, the authors use cross sectional and longitudinal data to show that distinct developmental windows of sensitivity to social media emerge in adolescence, dependent on age and sex.

Inherited disorders of neurotransmitter metabolism represent a group of rare neurometabolic diseases characterized by movement disorders and developmental delay. Here, the authors report a standardized evaluation of a registry of 275 patients from 42 countries, and highlight an evolving phenotypic spectrum of this disease group and factors influencing diagnostic processes.

Aromatic L-amino acid decarboxylase deficiency (AADC) is a rare neurodevelopmental disorder. Here the authors describe a clinical trial of MR-guided delivery of AAV2-AADC for the treatment of AADC.

People often change their preferences to conform with others. Using a longitudinal design, the authors show that such conformity decreases over the course of adolescence and that this reduction in conformity is accompanied by a decreasing degree of uncertainty about what to like.

People can infer unobserved causes of perceptual data (e.g. the contents of a box from the sound made by shaking it). Here the authors show that children compare what they hear with what they would have heard given other causes, and explore longer when the heard and imagined sounds are hard to discriminate.

Restricted and repetitive behaviors (RRBs) are a core clinical feature of autism, yet the brain basis of RRBs is unknown. Here, the authors demonstrate that aberrant cognitive control and motor circuit dynamics differentially predict three distinct symptom clusters that define RRBs.

The neurophysiological basis of neonatal responses to noxious stimulation is poorly understood. Using MRI, the authors observe that neonates’ noxious-stimulus evoked brain activity is coupled to both their resting-state network activity and white matter microstructure.

A reward-related ventral striatum response is observed when rewards are gained for friends. Here the authors examine how this response changes from childhood to young adulthood, and show that friendship stability in adolescence is associated with ventral striatum responses to vicarious rewards.

Kikuchi, Michikawa et al. investigate whether sleep quality and temperament in 1-month-old infants is associated with Autism Spectrum Disorder (ASD) in 3-year-old children in Japan. Infants who had longer daytime sleeps and more intense crying had a higher risk of ASD at age 3.

While the prognostic role of immunoglobulin heavy chain locus (IGH) rearrangement in minimal residual disease (MRD) in pediatric B-acute lymphoblastic leukemia (B-ALL) has been reported, the contribution of light chain loci (IGK/IGL) remains elusive. Here, the authors investigate it using a next generation sequencing approach.

Treatment of diffuse anaplastic Wilms tumours (DAWT) remains a challenge. Here, the authors perform multi-omic analysis and identify a desert-like DAWT subtype accounting for one third of DAWT cases and suggest treating them with HDAC and/or WEE1 inhibitors.

The role of clonal evolution on the actionable proteome and response to therapy in childhood acute lymphoblastic leukemia (ALL) remains unknown. Here, targeted sequencing and proteomic analysis of paired ALL diagnosis and relapsed samples revealed PARP1 as a potential therapeutic target.

The molecular mechanisms underlying relapse in pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patients remain to be explored. Here, the authors characterise the chromatin accessibility landscape of B-ALL and identify subtype and drug response specific patterns.

Yurchenko et al. describe a series of young xeroderma pigmentosum group C patients with early-onset gynecological tumors. DICER1 mutations are seen in all tumors, along with increased mutagenesis and a mutational profile characteristic of nucleotide excision repair deficiency.

Paediatric liver cancer is rare, and often associated with a predisposition syndrome. Here, the authors show that 11p15.5 mosaic alteration in the liver is a pre-neoplastic lesion associated with hepatoblastoma, and spatial transcriptomics together with single-nucleus RNAseq identify a an altered zonation in the liver of these patients.

Group 3 medulloblastomas (MBs) have the worst prognosis amongst the subtypes of MBs and are associated with MYC amplifications. Here the authors identify that mutations in CTDNEP1 cause MYC activation, amplification, and genomic instability in this subtype of MBs.

Brain metastases (BrMs) in non-small cell lung cancer (NSCLC) are associated with dismal outcomes, and are possibly sustained by the brain microenvironment. Here, the authors analyse NSCLC BrMs using Digital Spatial Profiling and reveal fibrosis, immune suppression, and cell reprogramming in the BrM microenvironment.

The availability of relevant animal models that can recapitulate high-risk hepatoblastoma will help to better understand its pathogenesis. Here the authors report and characterize a hepatocyte-specific, MYC-driven hepatoblastoma mouse model and show it recapitulates the human hepatoblastoma pathophysiology.

The cellular differentiation states of paediatric rhabdomyosarcoma (RMS) remain to be explored. Here, single-cell RNA sequencing analysis of RMS tumours reveals an immunosuppressive microenvironment and distinct transcriptional programs predictive of patient outcomes.

The development of neuroblastoma (NB) is regulated by multiple core transcription factors. Here, SOX11 is identified as a potential epigenetic master regulator upstream of the core regulatory circuitry in adrenergic high-risk neuroblastoma.

The biological underpinnings underlying the increased mortality and morbidity in adolescents and young adults (AYA) remains poorly understood. Here, the authors investigate the clinical and genomic disparities in AYA and older adults in a cohort of more than 100,000 cancer patients.

While recurrence is frequent in ependymoma, the underlying molecular mechanisms remain to be explored. Here, the authors investigate epigenetic, genetic and tumorigenic changes in 30 patient-matched repeated relapses over 13 years and identify distinct patterns of DNA methylation.

The genomic landscape of pediatric acute myeloid leukemia (AML) has mostly been characterised for Western populations. Here, the authors identify potential driver alterations in Chinese pediatric AML, which differ from Western populations, and propose a prognostic risk classification model.

Holst et al. study the relationship between cancer treatments and long-term health effects using registry data on childhood cancer survivors in Sweden. The authors utilize a causal inference approach to establish relationships between certain therapies and viral infections, eye conditions, and reproductive conditions, amongst others.

Retinoblastoma is the most frequent intraocular paediatric malignancy whose molecular basis remains poorly understood. Here, the authors perform multi-omic analysis and identify two subtypes; one in a cone differentiated state and one more aggressive showing cone dedifferentiation and expressing neuronal markers.

While hepatoblastoma is the most common pediatric liver cancer, its molecular background has not been fully characterised. Here, the authors perform genomic and epigenomic profiling of 163 untreated pediatric liver tumours and suggest the upregulation of ASCL2 and methylation patterns of IGF2 promoters in driving hepatoblast carcinogenesis.

Childhood neuroblastoma can be separated into high and low risk groups, with prognosis depending on age at diagnosis. Here, the authors show that low and high risk neuroblastoma tumours are composed of different cell types with different malignancy potential.

Patient-derived xenografts provide a resource for basic and translational cancer research. Here, the authors generate multiple pediatric high-grade glioma xenografts, use omics technologies to show that they are representative of primary tumours and use them to assess therapeutic response.

Transcriptomic analysis may provide information about the differentiation state and cell of origin of a cancer. Here, the authors assess mRNA signals in 1300 childhood and adult renal tumors and report a fetal origin of childhood tumors and no dedifferentiation of adult tumors.

Malignant rhabdoid tumours (MRT) have been suggested to originate in the ectoderm-derived neural crest. Here, the authors analyse MRTs using phylogenetics, scRNA-seq, and patient-derived organoids; they find evidence for an MRT origin in the neural crest lineage and suggest differentiation treatment with HDAC/mTOR inhibitors.

Paediatric therapy-related myeloid neoplasms (tMN) have a dismal prognosis and have not been comprehensively profiled. Here the authors characterise the molecular landscape of 84 paediatric tMN patients, and find that, unlike adult tMNs, these do not emerge from pre-existing clones and that MECOM dysregulation is frequent.

Oncogenic gene fusions are frequent in childhood cancers but remain poorly understood and untargeted. Here, the authors identify 272 oncogenic fusions in transcriptomics data from 5190 childhood cancer patients, revealing their possible etiologies, their links with tumor progression and evolution, and their potential as therapeutic targets.

Genomic landscape studies of malignant germ cell tumors (GCTs) that occur in children, adolescents and young adults are limited. Here the authors perform multi-omics profiling of different types of GCTs across the age spectrum from 0–24 years and show that WNT signalling pathway is activated in GCTs and is associated with poor clinical outcomes.

Fernández Villalobos, Marsall et al. analyzed seroprevalence and antibody responses to SARS-CoV-2 variants and endemic coronaviruses in Colombian children from urban and indigenous populations. They find high SARS-CoV-2 seroprevalence with comparable antibody titers but low neutralizing capacity and limited cross-protective immunity.

Kubisch et al. examine antibody seroconversion rates after SARS-CoV-2 infection in children attending daycare centers and adults in Germany. They found higher seroconversion rates in children compared with adults, which may have an influence on reinfection severity in the younger population.

Murray et al. conduct a systematic review, meta-analysis and modelling study to estimate the numbers of adverse perinatal outcomes attributable to HIV and antiretroviral therapy (ART) in sub-Saharan Africa from 1990 to 2020. They find that large numbers of adverse outcomes are attributable to HIV/ART, increasingly amongst women receiving preconception ART.

Here the authors show that SARS-CoV-2 vaccination and boosting, especially in the setting of previous infection, leads to significant increases in antibody levels and neutralizing activity against omicron BA.1 and BA.5 variants in both pregnant patients and their neonates.

Hou, Lai et al. estimate the impact of reports regarding a childhood vaccine with compromised efficacy on subsequent vaccination behaviors. The administration of the reported vaccine was delayed, while there was minimal effect on other vaccinations.

Severity of SARS-CoV-2 infection is different in adults and children which involves the immune response. Here using a parent and children cohort with 4 month and 12 month sampling times, the authors show enhanced levels and increased breadth of anti-spike antibody level over time but reduced specific T cell and B cell numbers in children.

Type I diabetes is characterized by autoantibodies directed against protein or non-protein self-antigens. Here the authors profile glycan reactive anti-carbohydrate antibodies (ACA) in a longitudinal and cross-sectional childhood diabetes cohort and associate clusters of ACA with disease progression.

In this disease mapping study, the authors estimate disability-adjusted life year rates for three of the major causes of mortality for children under five 43 countries in sub-Saharan Africa. They identify significant heterogeneity at the subnational level, highlighting the need for a targeted intervention approach.

The post-acute impacts of COVID-19 in children and adolescents are not well understood. In this population-based study in Geneva, the authors find evidence of COVID-19-related symptom persistence beyond 12 weeks in adolescents, and identify chronic conditions and lower socioeconomic status as risk factors.

Hand, foot and mouth disease, caused by enterovirus A71 (EV-A71) infection, is common in children in China. Here, the authors estimate EV-A71 incidence and seroprevalence using data from two longitudinal cohorts and find that, despite high infection rates, a large proportion of children under 6 are susceptible.

Despite a rise in COVID-19 cases among children, there is limited understanding of the antibody responses mounted, compared to in adults. In this work, authors compare seroconversion rates and antibody responses in unvaccinated Australian children across the three SARS-CoV-2 waves (Wuhan, Delta and Omicron).

Few countries have approved SARS-CoV-2 booster doses in children and adolescents due to insufficient evidence about the safety and interval vaccination. Here, the authors assess the safety and immunogenicity of a homologous booster dose of CoronaVac in a cohort of 3–17 year olds.

The identification of immune correlates of protection in humans would inform on the design and development of tuberculosis vaccine candidates. In this work, authors examine samples collected from South African infants, to determine whether the correlates of risk of tuberculosis disease, previously identified in this population, are also correlates of risk of M. tuberculosis infection.

Multisystem inflammatory syndrome may occur in children following COVID-19 infection. Here, the authors analyze gene signatures to show that MIS-C shares the same host immune response as the pre-pandemic inflammatory syndrome of Kawasaki disease but is further along in the spectrum in disease severity

Pregnant women have been disproportionately under-vaccinated against COVID-19, partly because they were excluded from initial trials. This systematic review and meta-analysis supports efficacy of vaccination in pregnancy, and finds no evidence of adverse maternal or perinatal outcomes.

Khanolkar et al. compare the immune response in perinatally-infected HIV+ patients with differing patterns of virological control on treatment with antiretroviral therapy. Patients with sub-optimally suppressed HIV displayed no deficits in lymphocyte functional fitness.

In this prospective cohort study, authors follow 328 households in Germany with at least one confirmed SARS-CoV-2 infection and find that children are more likely to seroconvert without symptoms and have higher specific antibody levels that persist longer than in adults.

Oral rotavirus vaccine (ORV) efficacy varies between countries, but underlying reasons aren’t fully understood. In this prospective cohort study, authors show that maternal rotavirus-specific antibodies in serum and breastmilk and pre-vaccination microbiota diversity are negatively correlated with ORV response in India and Malawi but not in the UK.

Identification of febrile children at risk of death in low-resource settings can improve survival, but tools for their prompt recognition are lacking. Here, the authors show that sTREM-1 measured at clinical presentation predicts in-hospital mortality in febrile children in Uganda.

Micronutrient supplements are key to global efforts to address child malnutrition. Here, in a cohort of children, previously enrolled into a large cluster randomized controlled trial of micronutrient supplementation in Pakistan, Popovic et al. find that vitamins and iron increase carriage of protozoa and fungi in the gut, potentially disrupting the bacterial microbiome.

Wurzel et al. describe the kinetics of the immune response in relation to clinical and virological features in a 5-month old infant with congenital heart disease and severe COVID-19. The immune response was characterised by an elevated inflammatory response in the acute phase of infection, followed by Th2 skewing and prolonged T cell activation.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

Respiratory syncytial virus (RSV) bronchiolitis during infancy is a major risk factor for asthma development. Here, Raita et al. integrate clinical data with airway microbiome, transcriptome, and metabolome data and identity four endotypes with differential risks for developing asthma.

The timing of measles vaccination in infants affects the risk of infection in young children and the duration of protection provided. Here, the authors investigate optimal vaccination timing by characterising antibody kinetics following different vaccine schedules in two cohorts of children in southern China.

This study investigates the impact of maternal COVID-19 vaccination during pregnancy on infant infection during the first six months of life. Using data from California, USA, the authors find that protection against infection during the period of Delta dominance was high, but that it declined during the Omicron period.

Giardia lamblia intestinal infection is independently associated with faltering linear growth in children in low-middle income countries, yet the mechanistic pathway has not been clearly identified. Authors utilise the MAL-ED cohort, and a gnotobiotic murine model, to explain Giardia-induced effects on childhood growth.

The antibody response of children to SARS-CoV-2 is less well studied than in adults. Here Hachim et al. show that children have reduced antibody levels to structural proteins and suggest that the predominance of antibody responses to non-structural proteins can be used to discriminate infection and vaccination.

The antibody response to the SARS-CoV-2 Omicron variant is not well studied in children. Here, the authors provide an age-stratified analysis of SARS-CoV-2 neutralizing capacity of sera from children with acute or convalescent COVID-19 as well as children with multisystem inflammatory syndrome.

Bordetella pertussis (Bp), the causative agent of pertussis, continues to circulate and it’s not well understood how (sub)clinical infections shape immune memory to Bp and vaccination. Here, using a mutant Bp strain lacking antigens of the acellular pertussis vaccine, the authors show how prior exposure to Bp shapes the mucosal antibody response to booster vaccination.