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Malnutrition enteropathy in Zambian and Zimbabwean children with severe acute malnutrition: A multi-arm randomized phase II trial
Childhood malnutrition in Africa is a glaring example of global inequality, and mortality remains high. Here, the authors report the results of the TAME randomized phase II clinical trial, in which intestinal healing was the target of four potential interventions in malnourished children in Zambia and Zimbabwe.
- Kanta Chandwe
- , Mutsa Bwakura-Dangarembizi
- & Paul Kelly
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Article
| Open Access
Perinatal outcomes after admission with COVID-19 in pregnancy: a UK national cohort study
The impacts of maternal SARS-CoV-2 infection on newborns are not well understood. Here, the authors perform a national cohort study using data on births in the UK from March 2020—March 2022 and find that moderate to severe maternal COVID-19 was associated with adverse perinatal outcomes.
- Hilde Marie Engjom
- , Rema Ramakrishnan
- & Marian Knight
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Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children
In this study, the authors assessed influenza-specific antibody responses in a cohort of seasonally vaccinated children and report that seasonal vaccination is beneficial by enhancing pandemic influenza virus-specific antibodies and cross-reactive effector functions.
- Janice Z. Jia
- , Carolyn A. Cohen
- & Sophie A. Valkenburg
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Early-life exercise induces immunometabolic epigenetic modification enhancing anti-inflammatory immunity in middle-aged male mice
Exercise could affect the immune system, but whether early-life exercise could benefit immune health in adulthood is not fully understood. Here the authors show that early-life exercise promotes epi-metabolic changes in the liver to potentially benefit immunity in older age and characterise the involvement of pipecolic acid in this process.
- Nini Zhang
- , Xinpei Wang
- & Feng Gao
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Comparative characterization of the infant gut microbiome and their maternal lineage by a multi-omics approach
Here, the authors employ multi-omics on a cohort comprising three generations of family members, showing that fecal microbiota populations, functions, and metabolome of infants vary greatly from their maternal lineage, exhibiting a less diverse microbiota and differences in various metabolite classes including short- and branched-chain fatty acids.
- Tomás Clive Barker-Tejeda
- , Elisa Zubeldia-Varela
- & Alma Villaseñor
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Geographic pair matching in large-scale cluster randomized trials
Geographic location can be a key determinant of human health outcomes. Here, the authors show that in large-scale trials, randomization that is pair matched by geography can lead to substantial improvements in statistical efficiency and enable insights into spatially varying intervention effects.
- Benjamin F. Arnold
- , Francois Rerolle
- & Jade Benjamin-Chung
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Protection against symptomatic dengue infection by neutralizing antibodies varies by infection history and infecting serotype
There is still a need to improve understanding of dengue-specific immunity. Here, by analyzing the antibody response in a pediatric cohort the authors show that the protective capacity of neutralizing antibodies depends on infection history and serotype, but its estimation varies by assay condition and virion maturation.
- Sandra Bos
- , Aaron L. Graber
- & Eva Harris
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Young infants display heterogeneous serological responses and extensive but reversible transcriptional changes following initial immunizations
Our understanding of the infant immune responses to routine vaccines remains limited. Here, the authors show that administration of routine vaccines to 2-month-old infants is associated with highly variable but limited antibody responses and mostly naïve-like immune cells with robust and transient expression of interferon genes.
- Nima Nouri
- , Raquel Giacomelli Cao
- & Octavio Ramilo
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Persistent humoral immune response in youth throughout the COVID-19 pandemic: prospective school-based cohort study
Understanding the immune responses of school-aged children to SARS-CoV-2 is important for designing public health measures. Here, the authors report findings from cross-sectional and longitudinal anti-SARS-CoV-2 antibody measurements in a school-based study in Zurich, Switzerland, from 2020-2022.
- Alessia Raineri
- , Thomas Radtke
- & Susi Kriemler
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Minimal residual disease detection by next-generation sequencing of different immunoglobulin gene rearrangements in pediatric B-ALL
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.
- Haipin Chen
- , Miner Gu
- & Xiaojun Xu
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Article
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The airway microbiota of neonates colonized with asthma-associated pathogenic bacteria
Here, Thorsen et al. bridge new and previous results from the COPSAC2000 prospective birth cohort and the later COPSAC2010 cohort, by constructing a combined bacterial pathogen score with implications for the early-life airway microbiota and the risk of asthma later in childhood
- Jonathan Thorsen
- , Xuan Ji Li
- & Jakob Stokholm
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Article
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Bifidobacteria shape antimicrobial T-helper cell responses during infancy and adulthood
The human immune system changes with age which impacts pathogen clearance. Here, Vogel et al. probe how CD4 + T-cells from different age groups respond to bacteria and show that activation with staphylococcal antigen induces T cells to become Th1-like cells, whilst stimulation with Bifidobacterium infantis induces a regulatory phenotype.
- Katrin Vogel
- , Aditya Arra
- & Monika C. Brunner-Weinzierl
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Social and psychological adversity are associated with distinct mother and infant gut microbiome variations
Here, in a cohort of mother-child dyads, the authors show that maternal prenatal social disadvantage and psychosocial stressors associate with distinct gut microbiome taxonomic and functional diversity in both the mothers and their four-month children.
- Barbara B. Warner
- , Bruce A. Rosa
- & Makedonka Mitreva
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Breastfeeding and impact on childhood hospital admissions: a nationwide birth cohort in South Korea
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.
- Jeong-Seon Lee
- , Jae Il Shin
- & Dong Keon Yon
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A comparative study of postnatal anthropometric growth in very preterm infants and intrauterine growth
The majority of growth references for preterm infants were assumed to reflect intrauterine growth. Here, the authors identify postnatal growth patterns of very preterm infants that are distinctly different than intrauterine growth.
- Fu-Sheng Chou
- , Hung-Wen Yeh
- & Reese H. Clark
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Metagenomic sequencing of post-mortem tissue samples for the identification of pathogens associated with neonatal deaths
Rapid identification of pathogens in neonatal infection, and corresponding antimicrobial susceptibility profiles, would improve patient outcomes and assist in antibiotic stewardship. In this work, the authors utilize metagenomic next-generation sequencing of post-mortem tissue samples to identify pathogens associated with neonatal deaths.
- Vicky L. Baillie
- , Shabir A. Madhi
- & Courtney P. Olwagen
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Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials
Nirsevimab binds the respiratory syncytial virus (RSV) fusion protein and has been tested for RSV prevention in clinical trials. Here, the authors analyse RSV from infections and show that binding site substitutions are rare and that over 99% of isolates remain susceptible to nirsevimab.
- Bahar Ahani
- , Kevin M. Tuffy
- & Tonya Villafana
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Article
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Asymptomatic immunodeficiency-associated vaccine-derived poliovirus infections in two UK children
There is increasing incidence of vaccine-derived poliovirus (VDPV) in countries thought to be polio free. Here, the authors report detection of VDPV in 2 UK children with primary immunodeficiency. The children did not develop paralysis, but isolated viruses showed intra-host evolution and neurovirulent potential.
- Anika Singanayagam
- , Dimitra Klapsa
- & Maria Zambon
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Characterisation of ASD traits among a cohort of children with isolated fetal ventriculomegaly
Isolated fetal ventriculomegaly is the most common antenatally-diagnosed brain abnormality. Here, the authors show that isolated fetal ventriculomegaly is associated with autism spectrum disorder traits.
- Vanessa Kyriakopoulou
- , Alice Davidson
- & Mary A. Rutherford
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Clinical NEC prevention practices drive different microbiome profiles and functional responses in the preterm intestine
Here, the authors comparatively analyze the impact of three successful clinical preventive interventions against NEC in preterm, VLBW infants and demonstrate a major impact of especially probiotic-based strategies on the development and maturation of the gut microbiome.
- Charlotte J. Neumann
- , Alexander Mahnert
- & Christine Moissl-Eichinger
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Maternal SARS-CoV-2 vaccination and infant protection against SARS-CoV-2 during the first six months of life
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.
- Ousseny Zerbo
- , G. Thomas Ray
- & Nicola P. Klein
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| Open Access
Nasal DNA methylation at three CpG sites predicts childhood allergic disease
Accurate prediction of the onset of childhood allergy is important to clarify the difference between various respiratory diseases. Here the authors propose that the methylation status of three sites in nasal DNA predicts the onset of childhood allergy which may aid diagnosis and monitoring.
- Merlijn van Breugel
- , Cancan Qi
- & Cheng-Jian Xu
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mTORC1 links pathology in experimental models of Still’s disease and macrophage activation syndrome
Still’s disease is an inflammatory syndrome linked to the development of further immune dysregulation and hypercytokinaemia termed macrophage activation syndrome. Here the authors implicate the mechanistic target of rapamycin complex 1 in murine models of Still’s disease and macrophage activation syndrome, and provide associations with clinical cases in patients
- Zhengping Huang
- , Xiaomeng You
- & Pui Y. Lee
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Seroepidemiology of enterovirus A71 infection in prospective cohort studies of children in southern China, 2013-2018
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.
- Juan Yang
- , Qiaohong Liao
- & Hongjie Yu
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Comparison of antibody responses to SARS-CoV-2 variants in Australian children
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).
- Zheng Quan Toh
- , Nadia Mazarakis
- & Paul V. Licciardi
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Mode of delivery modulates the intestinal microbiota and impacts the response to vaccination
The establishment and composition of the host microbiota is known to impact the function of the host immune response. Here the authors show that mode of delivery may impact the intestinal microbiota composition from birth and modulate the response to routine childhood vaccines.
- Emma M. de Koff
- , Debbie van Baarle
- & Susana Fuentes
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Article
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Integrated relationship of nasopharyngeal airway host response and microbiome associates with bronchiolitis severity
Bronchiolitis is major cause of infection, morbidity and hospitalisation. Here the authors apply transcriptomic based assessment of the host response, microbiome composition and function, and associate this to bronchiolitis severity.
- Michimasa Fujiogi
- , Yoshihiko Raita
- & Kohei Hasegawa
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Early treatment regimens achieve sustained virologic remission in infant macaques infected with SIV at birth
Neonates and infants infected with HIV generally develop disease rapidly, with early antiretroviral therapy (ART) often failing to achieve a sustained state of ART-free virologic remission. Here, the authors study viral reservoirs in neonatal macaques with early initiation of ART and an integrase inhibitor.
- Xiaolei Wang
- , Eunice Vincent
- & Huanbin Xu
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Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and infancy
Pregnant individuals are at higher risk of SARS-CoV-2-related morbidity and mortality, yet more studies are needed to evaluate safety and efficacy of vaccination during pregnancy, and also the level of protection provided to the newborn. Here, the authors evaluate transplacental transfer of mRNA vaccine products and functional SARS-CoV-2 antibodies during pregnancy and early infancy.
- Mary Prahl
- , Yarden Golan
- & Stephanie L. Gaw
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Maternal and perinatal obesity induce bronchial obstruction and pulmonary hypertension via IL-6-FoxO1-axis in later life
This study shows that maternal and perinatal obesity cause bronchial and vascular smooth muscle cell proliferation through an IL-6-FoxO1 axis, and favor thereby the emergence of bronchial obstruction and pulmonary hypertension later in life.
- Jaco Selle
- , Katharina Dinger
- & Miguel A. Alejandre Alcazar
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| Open Access
Early life inflammation is associated with spinal cord excitability and nociceptive sensitivity in human infants
More than 1 in 10 babies born in the UK are suspected of having an infection. Here the authors show that newborn babies with signs of infection (raised C-Reactive Protein levels) have exaggerated leg reflexes and pain-related brain activity following a heel prick blood test, suggesting they may be more sensitive to pain.
- Maria M. Cobo
- , Gabrielle Green
- & Rebeccah Slater
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Poor outcome of pediatric patients with acute myeloid leukemia harboring high FLT3/ITD allelic ratios
Activating FLT3 mutations are the most common mutations in AML. Here, the authors explore the relationship between the FLT3/ITD allelic ratio and prognosis in pediatric AML patients and identify an optimal threshold to stratify patients.
- Kun-yin Qiu
- , Xiong-yu Liao
- & Dun-hua Zhou
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Effective high-throughput RT-qPCR screening for SARS-CoV-2 infections in children
Dewald et al. combine a non-invasive sampling approach (Lolli-Test) with an RT qPCR-pool testing strategy to screen for SARS-CoV-2 infections in children and use the method for surveillance and infection control in > 4000 school and daycare settings.
- Felix Dewald
- , Isabelle Suárez
- & Florian Klein
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Pathophysiological pathway differences in children who present with COVID-19 ARDS compared to COVID -19 induced MIS-C
While rare, SARS-CoV-2-infected children can develop severe COVID-19 (ARDS) or inflammatory syndrome (MIS-C). Here, the authors use proteomics to characterize hundreds of blood proteins and identify key biological pathways that differentiate MIS-C and ARDS.
- Conor McCafferty
- , Tengyi Cai
- & Paul Monagle
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Article
| Open Access
Childhood body size directly increases type 1 diabetes risk based on a lifecourse Mendelian randomization approach
The rise in type 1 diabetes is thought to be related to increased childhood obesity, but this relationship is not well understood. In this study, the authors utilize Mendelian randomization to separate the direct and indirect effects of childhood body size on risk of type 1 diabetes and 7 other immune-associated disease outcomes.
- Tom G. Richardson
- , Daniel J. M. Crouch
- & George Davey Smith
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Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens in Niger
In a randomized placebo-controlled trial in rural Niger, biannual azithromycin distribution to children 1-59 months reduced all-cause mortality. Based on serology, Arzika et al. here report a reduction of Campylobacter infection, supporting one mechanism for the intervention’s impact on mortality.
- Ahmed M. Arzika
- , Ramatou Maliki
- & Benjamin F. Arnold
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| Open Access
Robust and durable serological response following pediatric SARS-CoV-2 infection
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.
- Hanna Renk
- , Alex Dulovic
- & Roland Elling
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Article
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Risk-stratification of febrile African children at risk of sepsis using sTREM-1 as basis for a rapid triage test
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.
- Aleksandra Leligdowicz
- , Andrea L. Conroy
- & Kevin C. Kain
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Article
| Open Access
Imprinted lncRNA Dio3os preprograms intergenerational brown fat development and obesity resistance
Maternal obesity predisposes offspring to obesity and metabolic disorders through incompletely understood mechanisms. Here the authors report that Dio3os is an imprinted long-coding RNA that modulates brown adipose tissue development and obesity resistance in the offspring.
- Yan-Ting Chen
- , Qi-Yuan Yang
- & Min Du
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Article
| Open Access
Identifying an optimal dihydroartemisinin-piperaquine dosing regimen for malaria prevention in young Ugandan children
Intermittent preventive treatment with dihydroartemisinin-piperaquine (DP) is protective in children against malaria. Here, the authors analyze plasma drug concentration, malaria incidence, and drug resistance markers from a clinical trial in Uganda and determine the optimal DP dosing regimen.
- Erika Wallender
- , Ali Mohamed Ali
- & Rada M. Savic
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Article
| Open Access
The composition of human vaginal microbiota transferred at birth affects offspring health in a mouse model
Exposure at birth to maternal microbiota has significant effects on offspring health and development. Here, the authors validate a model where inoculation of mice at birth with human vaginal microbiota produces significant effects on offspring health that are further amplified by an unhealthy prenatal environment.
- Eldin Jašarević
- , Elizabeth M. Hill
- & Tracy L. Bale
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Article
| Open Access
Analyses of child cardiometabolic phenotype following assisted reproductive technologies using a pragmatic trial emulation approach
Huang and colleagues used machine-learning estimators to analyse a broad range of parameters in a prospective cohort consisting ART and spontaneously conceived children. Small differences in stature and growth could not be explained by parental or perinatal environment factors, nor differences in fetal DNA methylation. No strong differences in metabolic parameters were seen.
- Jonathan Yinhao Huang
- , Shirong Cai
- & Shiao-Yng Chan
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Article
| Open Access
Insights into the expanding phenotypic spectrum of inherited disorders of biogenic amines
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.
- Oya Kuseyri Hübschmann
- , Gabriella Horvath
- & Thomas Opladen
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Article
| Open Access
Single-cell RNA sequencing of peripheral blood mononuclear cells from acute Kawasaki disease patients
Immune cell changes are associated with Kawasaki disease (KD) pathogenesis. Here, using single cell RNA sequencing of PBMC, the authors show monocyte inflammatory genes are over-expressed in KD and TCR and BCR clonotype sequences show oligoclonal expansions after intravenous immunoglobulin therapy.
- Zhen Wang
- , Lijian Xie
- & Min Huang
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Article
| Open Access
Gene therapy for aromatic L-amino acid decarboxylase deficiency by MR-guided direct delivery of AAV2-AADC to midbrain dopaminergic neurons
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.
- Toni S. Pearson
- , Nalin Gupta
- & Krystof S. Bankiewicz
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| Open Access
Integrated omics endotyping of infants with respiratory syncytial virus bronchiolitis and risk of childhood asthma
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.
- Yoshihiko Raita
- , Marcos Pérez-Losada
- & Kohei Hasegawa
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| Open Access
Infant gut microbiome composition is associated with non-social fear behavior in a pilot study
Experimental manipulation of the gut microbiome in animal models impacts fear behaviours. Here, the authors show in a pilot study that features of the human infant gut microbiome are associated with non-social fear behaviours during a laboratory based assessment.
- Alexander L. Carlson
- , Kai Xia
- & Rebecca C. Knickmeyer
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Article
| Open Access
Association between confirmed congenital Zika infection at birth and outcomes up to 3 years of life
Here, using diagnostic tools in a longitudinal cohort of ZIKV-infected pregnant women of the French Guiana Western Hospital Center (CHOG) and their infants, the authors investigate the long term neuropathological effects of congenital infection, finding that a laboratory confirmed congenital ZIKV infection at birth is associated with higher risks of adverse neurological outcomes up to three years of life.
- Najeh Hcini
- , Yaovi Kugbe
- & Léo Pomar
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Article
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Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1
Narcolepsy type 1 (NT1) is a severe sleep disorder with strong association to the HLA type DQB1*0602 and increased incidence among children vaccinated with the Influenza A vaccine Pandemrix. Here the authors show that these children develop T and B cell autoimmunity against protein-O-mannosyltransferase 1 via cross-reactivity.
- A. Vuorela
- , T. L. Freitag
- & O. Vaarala
Antiviral cellular therapy for enhancing T-cell reconstitution before or after hematopoietic stem cell transplantation (ACES): a two-arm, open label phase II interventional trial of pediatric patients with risk factor assessment