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Perspective
| Open Access
Less is more: Antibiotics at the beginning of life
Fear of missing neonatal sepsis has led to early in life antibiotic administration, even without culture-proven sepsis. Here, the authors discuss the potential impact on antimicrobial resistance, and chronic disease later in life, due to effect on the developing microbiome, suggesting a factual based approach in quantifying burden of treatment in relation to the burden of disease.
- Martin Stocker
- , Claus Klingenberg
- & Eric Giannoni
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Article
| Open Access
Strong pathogen competition in neonatal gut colonisation
Opportunistic bacterial pathogen species frequently colonise the human gut as a normal part of the ecosystem but strain-level colonisation and competition dynamics in healthy hosts is yet to be established. Authors seek to understand the relationship between colonisation potential and ecological factors modulating pathogen prevalence in disease in a longitudinal cohort.
- Tommi Mäklin
- , Harry A. Thorpe
- & Jukka Corander
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Article
| Open Access
Interrupted-time-series analysis of the immediate impact of COVID-19 mitigation measures on preterm birth in China
The broader impacts of COVID-19 mitigation measures may include changes in the incidence of preterm birth. Here, the authors use data from ~11.7 million pregnancies in China and find evidence of a small decline in preterm birth rates immediately following the implementation of COVID-19 mitigation measures.
- Yanxia Xie
- , Yi Mu
- & Jun Zhu
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Article
| Open Access
Cross-sectional seroprevalence surveys of SARS-CoV-2 antibodies in children in Germany, June 2020 to May 2021
Children are less likely to be infected with SARS-CoV-2 and develop less severe disease than adults, which makes estimation of infection rates challenging. Here, the authors conduct seroprevalence surveys of children in Germany, describe changes in prevalence over time, and identify risk factors for infection.
- Anna-Lisa Sorg
- , Leon Bergfeld
- & Horst Schroten
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Article
| Open Access
Effects of early-life antibiotics on the developing infant gut microbiome and resistome: a randomized trial
Here, in a randomized trial of 147 infants receiving distinct antibiotic regimens for early-onset neonatal sepsis, Reyman et al. characterize the gut microbiome and resistance profiles, finding differential effects of antibiotic combinations on microbial community composition and antimicrobial resistance genes.
- Marta Reyman
- , Marlies A. van Houten
- & Debby Bogaert
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Article
| Open Access
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
Ensembled deep learning model outperforms human experts in diagnosing biliary atresia from sonographic gallbladder images
It is still challenging to make accurate diagnosis of biliary atresia (BA) with sonographic gallbladder images particularly in rural areas without relevant expertise. Here, the authors develop a diagnostic deep learning model which favourable performance in comparison with human experts in multi-center external validation.
- Wenying Zhou
- , Yang Yang
- & Luyao Zhou
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Article
| Open Access
Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19
Children with SARS-CoV-2 infection are more likely to have mild symptoms and may be asymptomatic, but underlying reasons remain unclear. Here, the authors show cellular, cytokine and antibody response to SARS-CoV-2 infection in three children who repeatedly tested negative for the virus by PCR, despite high exposure in the household.
- Shidan Tosif
- , Melanie R. Neeland
- & Nigel W. Crawford
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Article
| Open Access
Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak
COVID-19 disease is less common in children than adults, but the extent to which SARS-CoV-2 infections are missed through symptom-driven testing is not well understood. In this study, the authors show that approximately 1% of children seeking care for reasons other than COVID-19 at a Seattle hospital in March/April 2020 were seropositive for SARS-CoV-2.
- Adam S. Dingens
- , Katharine H. D. Crawford
- & Jesse D. Bloom
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Article
| Open Access
Transplacental transmission of SARS-CoV-2 infection
Congenital infection of SARS-CoV-2 has been described, but the transmission routes remain unclear. Here, the authors report evidence of transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the last trimester and presenting with neurological compromise.
- Alexandre J. Vivanti
- , Christelle Vauloup-Fellous
- & Daniele De Luca
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Article
| Open Access
Oil-in-water emulsion adjuvants for pediatric influenza vaccines: a systematic review and meta-analysis
Here, the authors meta-analyze clinical trials comparing adjuvanted and non-adjuvanted influenza vaccines in children and find that oil-in-water emulsion adjuvant improves the efficacy of inactivated influenza vaccines in healthy immunologically naive children.
- Yu-Ju Lin
- , Chiao-Ni Wen
- & Chi-Tai Fang
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Article
| Open Access
Impact of delivery mode-associated gut microbiota dynamics on health in the first year of life
Here, in a cohort of infants unexposed to maternal antibiotics, the authors analyse the gut microbiome development of children born naturally and by caesarean section, finding a higher abundance of known pathogens in the latter group, and an association between these bacteria and a higher incidence of respiratory infections in the first year of life.
- Marta Reyman
- , Marlies A. van Houten
- & Debby Bogaert
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Article
| Open Access
Genome-wide association study reveals dynamic role of genetic variation in infant and early childhood growth
Changes in body mass index (BMI) during infancy and childhood follow a well-characterized pattern. Here, Helgeland et al. perform genome-wide association studies for BMI at 12 time points between birth and 8 years of age and find transient associations at the LEP and LEPR loci.
- Øyvind Helgeland
- , Marc Vaudel
- & Pål Rasmus Njølstad
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Article
| Open Access
A child with perinatal HIV infection and long-term sustained virological control following antiretroviral treatment cessation
Some perinatally HIV infected children who have received early antiretroviral therapy (ART) show long-term sustained virological control after ART cessation. Here the authors describe a case who, at age 9.5 years, shows normal CD4:CD8 T cell ratios and has no detectable levels of replication-competent virus.
- Avy Violari
- , Mark F. Cotton
- & Caroline T. Tiemessen
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Article
| Open Access
Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential
The effects of caesarean section delivery on mother-to-neonate transmission of microbiota are unclear. Here the authors show that caesarean section delivery can affect the transmission of specific microbial strains and the immunomodulatory potential of the microbiota.
- Linda Wampach
- , Anna Heintz-Buschart
- & Paul Wilmes
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Article
| Open Access
A key genetic factor for fucosyllactose utilization affects infant gut microbiota development
The factors shaping the development of infants' gut microbiota are poorly understood. Here, the authors show that alterations in gut microbiota development in infants are associated with the presence of bifidobacteria having a gene for utilisation of human milk oligosaccharides.
- Takahiro Matsuki
- , Kana Yahagi
- & Ken Kurokawa
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Article
| Open Access
T-cell activation is an immune correlate of risk in BCG vaccinated infants
BCG vaccine confers only partial protection against tuberculosis. Here the authors show that the risk of tuberculosis infection and progression to disease in BCG-immunized children positively correlates with the frequency of activated HLA-DR+CD4+T cells.
- Helen A. Fletcher
- , Margaret A. Snowden
- & Helen McShane
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Article
| Open Access
Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans
Exposure to childhood trauma is a major risk factor for the development of almost all psychiatric disorders. By epigenome-wide studies, here, Houtepen et al. show that DNA methylation at a locus in the Kit ligand gene (KITLG) mediates the relationship between childhood trauma and cortisol stress reactivity.
- Lotte C. Houtepen
- , Christiaan H. Vinkers
- & Marco P. M. Boks
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Article
| Open Access
Neural dynamics of prediction and surprise in infants
Prior expectations shape neural processing in the brain and violations of these expectations can have a profound influence on learning. Here the authors demonstrate that such predictive coding mechanisms are already functional in the brains of 12-month-old infants.
- Sid Kouider
- , Bria Long
- & Sofie V. Gelskov
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Article
| Open Access
Genetic sharing and heritability of paediatric age of onset autoimmune diseases
Autoimmune diseases are genetically complex disorders that affect up to 10% of the Western population. Here Li et al. quantify the heritability of a range of autoimmune diseases in the largest paediatric cohort examined to date, illustrating that genetic and non-genetic components variably contribute to the susceptibility of each disease.
- Yun R. Li
- , Sihai D. Zhao
- & Hakon Hakonarson
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Article
| Open Access
Maternal bile acid transporter deficiency promotes neonatal demise
The mechanisms underlying perinatal mortality due to intrahepatic cholestasis of pregnancy are not fully understood. Here, the authors show that absence of the nuclear receptor and bile acid regulator Nrli2 and the biliary transporter Abcb11 strongly reduces maternal serum bile acid levels, improving neonatal survival.
- Yuanyuan Zhang
- , Fei Li
- & John D. Schuetz
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Article
| Open Access
Genome-wide association study identifies new susceptibility loci for adolescent idiopathic scoliosis in Chinese girls
The authors perform a genome-wide association study of adolescent idiopathic scoliosis patients of Han Chinese descent, and identify 3 new loci for disease susceptibility.
- Zezhang Zhu
- , Nelson Leung-Sang Tang
- & Jack Chun-Yiu Cheng
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Editing the genome to introduce a beneficial naturally occurring mutation associated with increased fetal globin
Adult expression of fetal haemoglobin is beneficial and thus desirable in patients with haemoglobin disorders. Here the authors introduce a naturally occurring mutation in the γ-globinpromoter and show that it causes binding of an activator TAL1, chromosome looping and revival of fetal haemoglobin expression in erythroid cells.
- Beeke Wienert
- , Alister P. W. Funnell
- & Merlin Crossley
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Article
| Open Access
Trained immunity in newborn infants of HBV-infected mothers
The ability to fight infections matures after birth and is thus termed ‘trained immunity’. Here the authors show that cord blood cells from hepatitis B virus-infected mothers respond more strongly to bacterial infections, suggesting that viral exposure in uteropromotes trained immunity in newborns.
- Michelle Hong
- , Elena Sandalova
- & Antonio Bertoletti
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Genome-wide association study identifies a new susceptibility locus for cleft lip with or without a cleft palate
Cleft lip is one of the most common congenital birth defects with substantial impairments to quality of life. Here, Sun et al. identify a new locus associated with cleft lip in diverse Chinese populations.
- Yimin Sun
- , Yongqing Huang
- & Yinxue Yang
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Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children
Food allergy is a growing clinical and public health burden. Here, the authors carry out a genome-wide association study in samples with well-defined allergies to a variety of foods, and identify the 6p21.32 region that significantly increases risk of developing peanut allergy.
- Xiumei Hong
- , Ke Hao
- & Xiaobin Wang
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Article
| Open Access
Generalization of word meanings during infant sleep
In adults, oscillatory brain activity during sleep is related to memory consolidation. Here, the authors measure brain activity from infants who are exposed to novel word meanings, and show that infant sleep results in the retention and reorganization of recently encoded memories.
- Manuela Friedrich
- , Ines Wilhelm
- & Angela D. Friederici
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Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness
Blindness due to retinal degeneration affects millions of people worldwide, but many disease-causing mutations remain unknown. Here the authors link mutations in the gene PNPLA6 with childhood blindness in seven families with retinal degeneration and show that the gene plays a role in photoreceptor survival in Drosophila.
- S. Kmoch
- , J. Majewski
- & R. K. Koenekoop
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Mybpc3 gene therapy for neonatal cardiomyopathy enables long-term disease prevention in mice
Hereditary hypertrophic cardiomyopathy (HCM) is caused by mutations in cardiomyocyte genes, such as MYBPC3. Here, the authors use virus-mediated gene therapy to correct Mycbpc3mutations in 1-day-old mice and, by administering just a single dose, prevent development of HCM over a period of 34 weeks.
- Giulia Mearini
- , Doreen Stimpel
- & Lucie Carrier
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Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia
Epigenetic regulators have been proposed to be modulators of chemoresistance in acute lymphoblastic leukaemia. Here, the authors find enrichment of mutations in epigenetic regulators at relapse, including somatic mutations in SETD2.
- Brenton G. Mar
- , Lars B. Bullinger
- & Scott A. Armstrong
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Article
| Open Access
Estimating the potential public health impact of seasonal malaria chemoprevention in African children
Seasonal malaria chemoprevention can lower the incidence of malaria in areas where transmission is highly periodical. Combining data on rainfall, population and malaria endemicity, Cairnset al. identify geographical areas in sub-Saharan Africa where this intervention is likely to be effective and cost-effective.
- Matthew Cairns
- , Arantxa Roca-Feltrer
- & Brian M. Greenwood
A comparative study of postnatal anthropometric growth in very preterm infants and intrauterine growth