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Many hospitalised children with acute illness in low- and middle-income countries experience incomplete recovery, readmission, and post-discharge mortality despite guideline-directed care. Here the authors report multiomic profiling to investigate biological drivers of hospital in-patient and post-discharge mortality in 3,101 acutely ill children across nine sites in sub-Saharan Africa and South Asia.

Long-term effects of in utero Chikungunya exposure are not well characterized, although intrapartum exposure is known to be associated with neonatal mortality. Here, the authors assess risk of all-cause hospitalization and mortality up to three years following in-utero exposure in a cohort from Brazil.

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease of premature infants with unclear mechanisms. Here, the authors show that CD177⁺ neutrophil–platelet aggregates promote neutrophil extracellular trap (NET)-linked thromboinflammation in NEC and that blocking CD177/NET formation or low-molecular-weight heparin alleviates disease in mouse models.

This study reveals three distinct brain patterns in insufficient sleep adolescents, each linked to unique factors of genetics, environmental disturbances, or psychiatric risk.

Yang, Zeng et al. investigate associations between maternal metabolic profiles during early pregnancy and offspring development using untargeted metabolomics in the Shanghai Birth Cohort. Several metabolites are associated with offspring birth weight and cognitive development in childhood and reflect sex-specific patterns.

Wonkam et al. use whole-exome sequencing of 46 multiplex Cameroonian families, alongside cell-based assays and a knockout mouse model, to identify genetic causes of hearing impairment. They find a high diagnostic yield with MYO15A and TMC1as the most common genes, identify three candidate genes SUN2, TGM6, and TMC3, and show that SUN2 is unlikely to be causal, underscoring both the genetic diversity in African populations and the opportunities for future gene-therapy–relevant discoveries.

In this target trial emulation study, the authors evaluate effectiveness of nirmatrelvir/ritonavir in non-hospitalized paediatric patients aged 12–17 years with SARS-CoV-2 Omicron infection and show reduced risks of 28 day all-cause mortality or hospitalization associated with the treatment.

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).

This study identifies protein signatures of pediatric obesity linked to cardiometabolic risk, shows treatment-related changes, and highlights a three-protein panel predictive of steatotic liver disease for early diagnosis

This illustrated PrimeView highlights rhabdomyosarcoma epidemiology, disease mechanisms, diagnosis, risk-based disease management, and prevention of late treatment effects.

Motile ciliopathies are rare genetic diseases that result in defective beating of motile cilia on epithelial cells. This PrimeView highlights the epidemiology, mechanisms, diagnosis and management of motile ciliopathies, and summarizes possible future research.

This PrimeView highlights the mechanisms of Paediatric functional abdominal pain disorders (FAPDs), and accompanies the Primer article on Paediatric FAPDs by Enck and colleagues.

This PrimeView highlights the management strategies for bronchopulmonary dysplasia, a form of chronic lung dysfunction that results from lung and airway injury caused by respiratory support measures in (predominantly premature) newborn babies.

Piri et al. analyze blood gene expression profiles in children hospitalized for suspected severe infections to identify transcriptomic markers distinguishing bacterial from viral causes. They identify a two-gene signature, TSPO and SECISBP2, that accurately differentiates bacterial and viral infections across diverse clinical presentations.

Seiler et al. use statistical learning to analyze co-occurrence patterns of child malnutrition in sub-Saharan Africa, examining indicators such as hemoglobin and height-for-age. The findings reveal strong correlations and spatio-temporal variability, highlighting the need for targeted interventions to address these issues.

Here, the authors identify distinct, autism-specific diet microbiome interactions, showing how unhealthy diets and synthetic emulsifiers drive dysbiosis. The findings pave the way for microbiome-aware dietary strategies for autism.

The authors show that babies conceived during the COVID-19 pandemic have a different parental socioeconomic composition than expected had the pandemic not occurred.

Here the authors show that gut metagenomes of Indigenous Australian infants living remotely, display greater diversity and abundance of bacteria, viruses and fungi, compared to non-Indigenous infants living in urban Australia, suggesting that while having access to Western foods, the infants start life with a gut microbiome that retains key features of pre-industrialized societies.

Designing therapeutics for children requires careful consideration of age-dependent anatomy, physiology and immunology. This Review discusses the engineering and optimization of drug delivery systems for paediatric microenvironments to prevent, treat and cure childhood diseases.

Here, in a randomized clinical trial, the authors report that an experimental young child formula containing a combination of Limosilactobacillus reuteri DSM 17938 and galacto-oligosaccharides enhances bone and muscle development in early life through modulation of the microbiome.

Birth season has been associated with differences in epigenetic, developmental and health outcomes, but associations to developing metabolome are unclear. Here the authors report a secondary exploratory analysis of The Early Life Interventions for Childhood growth and development in Tanzania (ELICIT) trial showing that in rural Tanzania, an infant’s birth season shapes their metabolism up to 18 months of life, linked to rainfall, food insecurity and breastmilk composition.

Esser et al. conducted a nationwide survey of 201 health and social care professionals in Germany on the mental health care of asylum-seeking and refugee minors. Results show that mental health problems are frequent but rarely followed up with major barriers due to limited screening, communication difficulties, and insufficient care structures.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Children born to women living with HIV suffer increased morbidity and, in low-income settings, have two to three times the mortality of infants born to women without HIV. Here, we profile the milk metabolome of 326 women living with and without HIV sampled longitudinally for 18 months postpartum using global metabolomics. Our findings demonstrate that milk tryptophan content and availability decrease among WLWH, which may indicate perturbations in milk tryptophan catabolism.

Children living with HIV face a heightened risk of iron deficiency, yet optimal prevention and treatment strategies remain elusive. In these three prospective studies in South African children living with HIV, the authors show reduced dietary iron absorption but adequate absorption from iron supplements. Prebiotics may enhance efficacy and safety of oral iron supplementation in iron-deficient children living with HIV.

Neutrophils infiltrate the ischemic brain. Here, the authors show a disease-stage dependent neutrophil diversification in neonatal brain injury; neutrophils aggravating tissue damage in the acute phase while promoting regeneration in the later stage.