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Age-related gut bacterial changes during infancy have been widely studied, but it remains still unknown how these changes are associated with immune cell composition. This study's aim was to explore if the temporal development of gut bacteria during infancy prospectively affects immune cell composition. Faecal bacteria and short-chain fatty acids were analysed from 67 PreventADALL study participants at four timepoints (birth to 12 months) using reduced metagenome sequencing and gas chromatography. Immune cell frequencies were assessed using mass cytometry in whole blood samples at 12 months. The infants clustered into four groups based on immune cell composition: clusters 1 and 2 showed a high relative abundance of naïve cells, cluster 3 exhibited increased abundance of classical- and non-classical monocytes and clusters 3 and 4 had elevated neutrophil levels. At all age groups, we did observe significant associations between the gut microbiota and immune cell clusters; however, these were generally from low abundant species. Only at 6 months of age we observed significant associations between abundant (>8%) species and immune cell clusters. Bifidobacterium adolescentis and Porphyromonadaceae are associated with cluster 1, while Bacteroides fragilis and Bifidobacterium longum are associated with clusters 3 and 4 respectively. These species have been linked to T-cell polarization and maturation. No significant correlations were found between short-chain fatty acids and immune cell composition. Our findings suggest that abundant gut bacteria at 6 months may influence immune cell frequencies at 12 months, highlighting the potential role of gut microbiota in shaping later immune cell composition.
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Fezes , Microbioma Gastrointestinal , Humanos , Lactente , Microbioma Gastrointestinal/imunologia , Masculino , Feminino , Fezes/microbiologia , Recém-Nascido , Bactérias/imunologia , Bactérias/classificação , Ácidos Graxos Voláteis/metabolismo , Metagenoma , Estudos ProspectivosRESUMO
Background: Smoking in pregnancy has detrimental effects on infant respiratory health, while the effects of other nicotine-containing products on infant lung function are unclear. We aimed to explore if smokeless tobacco such as snus used in pregnancy increased the risk of lower lung function in infancy and if the associations differed by sex. Methods: From the Scandinavian population-based Preventing Atopic Dermatitis and ALLergies in Children birth cohort, we included 1163 infants with available tidal flow-volume measurements at 3â months of age and maternal self-reported use of nicotine-containing products in pregnancy. The risk of a ratio of time to peak tidal expiratory flow to total expiratory time <25th percentile by any nicotine exposure, snus exclusively and cigarette smoking with or without other nicotine-containing products was explored by regression analyses adjusting for maternal age, education and asthma. Results: Overall 120 out of 1163 (10.3%) infants were exposed to any nicotine in utero, 71 out of 120 by snus exclusively and 49 out of 120 by smoking, with six also exposed to snus. By pregnancy week 6, 85.8% of mothers reported stopping nicotine use. The risk of lower lung function was higher in children exposed in utero to nicotine-containing products with an odds ratio (OR) of 1.63 (95% confidence interval (CI) 1.02-2.59) with a similar tendency for snus exclusively (OR 1.55, 95% CI 0.88-2.71) and smoking (OR 1.79, 0.84-3.84). Effect estimates were similar after adjusting for covariates. No differences of the effect by sex were observed. Conclusion: Our study suggests that in utero exposure to not only cigarettes, but also snus, may negatively affect infant lung function.
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INTRODUCTION: Knowledge on prevalence and association of human papillomavirus (HPV) in third trimester placentae and adverse pregnancy outcomes is limited. We investigated the prevalence of placental HPV at delivery, explored urine HPV characteristics associated with placental HPV and whether placental HPV increased the risk adverse pregnancy outcomes. METHODS: Pregnant women were enrolled in the Scandinavian PreventADALL mother-child cohort study at midgestation. Human papillomavirus genotyping was performed on placental biopsies collected at delivery (n = 587) and first-void urine at midgestation and delivery (n = 556). Maternal characteristics were collected by questionnaires at gestational week 18 and 34. Adverse pregnancy outcomes were registered from chart data including hypertensive disorders of pregnancy, gestational diabetes mellitus and newborns small for gestational age. Uni- and multivariable regression models were used to investigate associations. RESULTS: Placental HPV was detected in 18/587 (3 %). Twenty-eight genotypes were identified among the 214/556 (38 %) with midgestational urine HPV. Seventeen of the 18 women with placental HPV were midgestational HPV positive with 89 % genotype concordance. Midgestational high-risk-(HR)-HPV and high viral loads of Any- or HR-HPV were associated with placental HPV. Persisting HPV infection from midgestation to delivery was not associated with placental HPV. Adverse pregnancy outcomes were seen in 2/556 (0.4 %) of women with placental HPV. DISCUSSION: In this general cohort of pregnant women, the prevalence of placental HPV was 3 %, and midgestational urinary HPV 38 %. High HPV viral load increased the risk for placental HPV infections. We observed no increased risk for adverse pregnancy outcomes in women with placental HPV.
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Infecções por Papillomavirus , Placenta , Complicações Infecciosas na Gravidez , Resultado da Gravidez , Humanos , Feminino , Gravidez , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Adulto , Placenta/virologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Papillomaviridae/genética , Estudos de Coortes , Terceiro Trimestre da Gravidez , Adulto JovemRESUMO
Background: It is estimated that 65 million people worldwide suffer from long covid (LC). Many LC symptoms are also reported by patients with airflow limitation, used to confirm asthma. The primary aim was to detect airflow limitation in LC patients by a methacholine bronchial provocation test (BPT) and if negative, by evaluation of diurnal variability in forced expiratory flow in 1 second (FEV1) over a two-weeks' period. The second aim was to assess responsiveness to asthma treatment on diurnal FEV1 variability and LC symptoms. Methods: Patients with LC for at least six months were recruited in this open diagnostic study. Burden of LC symptoms were reported on a 10-point Likert scale (0 = not troubled, 10 = extremely troubled) at inclusion and after three weeks' asthma treatment. A positive methacholine BPT was defined by an accumulated provocation dose (PD20)<8 µmol causing 20% fall in FEV1. App-based spirometer was used for diurnal FEV1 variability, deemed positive by diurnalvariability in FEV1 ≥12%. Results: Airflow limitation was documented by positive methacholine BPT in 8/30 (27%), or by excessive diurnal variability in FEV1 in 21/22 (95%) of the BPT negative LC patients. One patient dropped out due to personal issues. Three weeks' asthma treatment normalised mean diurnal FEV1 variability from 18.0% to 7.3%, p < 0.001. Significant reductions were observed for fatigue and dyspnoea, from 8.3 to 6.1, p < 0.001, and 3.0 to 0, p < 0.001, respectively. Conclusion: This study indicate that airflow limitation may be detected in many LC patients if evaluation of diurnal variability in FEV1 is included in the diagnostics.
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BACKGROUND: In the general population randomized controlled trial PreventADALL, frequent emollient bath additives from 2 weeks of age did not prevent atopic dermatitis, while the effect on skin barrier function throughout infancy is not established. OBJECTIVES: The primary aim of this exploratory substudy was to assess the effect of mineral-based oil baths on transepidermal water loss (TEWL) and dry skin through infancy, and secondarily to explore if filaggrin (FLG) mutations modified the effect. METHODS: Overall, 2153 infants were included and randomized to either the 'Skin intervention' (SI) group (n = 995) (oil bath 4 times weekly from 2 weeks through 8â months) or 'No skin intervention' (NSI) group (n = 1158), with TEWL measurements at 3, 6 and/or 12â months of age. Information on FLG mutation status was available for 1683 of these infants. Effects of the skin intervention on TEWL and dry skin through infancy were assessed by mixed-effects regression modelling. Background characteristics and protocol adherence were collected from electronic questionnaires, birth records and weekly diaries. RESULTS: The TEWL (95% confidence interval) was on average 0.42â g m-2 h-1 (0.13-0.70, P = 0.004) higher in the SI group compared with the NSI group through the first year of life, with significantly higher levels at 3â months [8.6 (8.3-9.0) vs. 7.6 (7.3-7.9)], but similar at 6 and 12â months. Dry skin was observed significantly more often in the NSI group compared with the SI group at 3â months (59% vs. 51%) and at 6â months of age (63% vs. 53%), while at 12â months of age, the difference was no longer significant. At 3â months, the TEWL of FLG mutation carriers was similar to the TEWL in the SI group. No interaction between SI and FLG mutation was found in the first year of life. CONCLUSIONS: Infants given frequent oil baths from 2 weeks of age had reduced skin barrier function through infancy compared with controls, largely attributed to higher TEWL at 3â months of age, while the skin at 3 and 6â months appeared less dry in infants subjected to the skin intervention.
Atopic dermatitis (AD) affects approximately 20% of children in industrialized countries. AD causes dry, itchy skin and can increase the chance of infections. This study was a substudy of the large Scandinavian PreventADALL trial, including 2394 infants, recruited from the general population between 2014 and 2016. Children in this trial were allocated randomly to receive either a skin intervention, food intervention, combined intervention, or no intervention. Children were examined at 3, 6 and 12â months of age. The examinations involved an investigation of the skin, to evaluate dry skin and skin barrier function by transepidermal water loss (TEWL) in the outer layers of the skin (higher TEWL suggests decreased skin barrier function). The skin intervention consisted of oil baths at least 4 times per week from 2 weeks of age through 8â months of age, and have previously not been shown to prevent AD by 1 and 3â years of age. We aimed to investigate whether frequent oil baths had any effect on TEWL and dry skin. We found that the skin intervention increased TEWL in the first year of life, especially at 3â months of age. Dry skin was less common in the skin intervention groups compared with the groups with no skin intervention. Infants with mutations in the gene coding for a skin barrier protein, called filaggrin, were associated with increased TEWL; however, in the skin intervention group, TEWL was similar among the infants with or without filaggrin mutations. Our findings suggest that oil baths several times per week from early infancy transiently decreases skin barrier function.
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Banhos , Dermatite Atópica , Emolientes , Proteínas Filagrinas , Proteínas de Filamentos Intermediários , Mutação , Perda Insensível de Água , Humanos , Perda Insensível de Água/efeitos dos fármacos , Banhos/métodos , Lactente , Feminino , Dermatite Atópica/prevenção & controle , Dermatite Atópica/genética , Masculino , Emolientes/administração & dosagem , Proteínas de Filamentos Intermediários/genética , Recém-Nascido , Óleo Mineral/administração & dosagem , Cuidado do Lactente/métodos , Higiene da Pele/métodos , Pele/efeitos dos fármacosRESUMO
BACKGROUND: Largely unexplored, we investigated if lower lung function, impaired skin barrier function by transepidermal water loss (TEWL), eczema, and filaggrin (FLG) mutations in infancy were associated with asthma in early childhood. METHODS: From the factorially designed randomized controlled intervention study PreventADALL, we evaluated 1337/2394 children from all randomization groups with information on asthma at age 3 years, and at age 3 months either lung function, TEWL, eczema, and/or FLG mutations. Lower lung function was defined as the time to peak tidal expiratory flow to expiratory time (tPTEF /tE ) <0.25, and skin barrier impairment as a high TEWL >9.50 g/m2 /h. Eczema was clinically observed, and DNA genotyped for FLG mutations. Asthma was defined as asthma-like symptoms (≥3 episodes of bronchial obstruction) between age 2-3 years as well as a history of doctor-diagnosed asthma and/or asthma medication use. Associations were analyzed in logistic regression models, presented with adjusted ORs (aOR) and 95% confidence intervals (CI). RESULTS: Lower lung function and skin barrier impairment were associated with asthma in general; aOR (95% CI) 5.4 (2.1, 13.7) and 1.6 (1.1, 2.5), while eczema and FLG mutations were associated with asthma in children with atopic dermatitis or allergic sensitization only. Stratifying for sex, the risk of asthma was only increased in boys with lower lung function; aOR (95% CI) 7.7 (2.5, 23.6), and in girls with FLG mutations; aOR (95% CI) 3.5 (1.5, 8.2). CONCLUSION: Lower lung function and impaired skin barrier function in infancy may increase the risk of asthma at age 3 years.
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Asma , Dermatite Atópica , Eczema , Criança , Lactente , Masculino , Feminino , Humanos , Pré-Escolar , Eczema/epidemiologia , Eczema/genética , Asma/epidemiologia , Asma/genética , Asma/complicações , Dermatite Atópica/diagnóstico , Genótipo , Mutação , Pulmão , Proteínas de Filamentos Intermediários/genéticaAssuntos
Asma , Hipersensibilidade , Humanos , Alérgenos , Coorte de Nascimento , Hipersensibilidade/epidemiologiaRESUMO
Background: Birth by caesarean section (CS) is associated with development of allergic diseases, but its role in the development of atopic dermatitis (AD) is less convincing. Objective: Our primary aim was to determine if birth mode was associated with AD in 3-year-olds and secondarily to determine if birth mode was associated with early onset and/or persistent AD in the first 3 years of life. Methods: We included 2129 mother-child pairs from the Scandinavian population-based prospective PreventADALL cohort with information on birth mode including vaginal birth, either traditional (81.3%) or in water (4.0%), and CS before (6.3%) and after (8.5%) onset of labor. We defined early onset AD as eczema at 3 months and AD diagnosis by 3 years of age. Persistent AD was defined as eczema both in the first year and at 3 years of age, together with an AD diagnosis by 3 years of age. Results: AD was diagnosed at 3, 6, 12, 24, and/or 36 months in 531 children (25%). Compared to vaginal delivery, CS was overall associated with increased odds of AD by 3 years of age, with adjusted odds ratio (95% confidence interval) of 1.33 (1.02-1.74), and higher odds of early onset AD (1.63, 1.06-2.48). The highest odds for early onset AD were observed in infants born by CS after onset of labor (1.83, 1.09-3.07). Birth mode was not associated with persistent AD. Conclusion: CS was associated with increased odds of AD by 3 years of age, particularly in infants presenting with eczema at 3 months of age.
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INTRODUCTION: Eosinophil-derived neurotoxin (EDN) is related to childhood asthma, while normal values are lacking. We aimed to document serum EDN levels at 1 and 3 years in general and in non-atopic children, and explore if EDN levels differed by sex or were associated with preschool asthma at 3 years. METHODS: From the PreventADALL birth cohort, we included 1233 children with EDN analysed using ImmunoCAP at 1 and/or 3 years. Non-atopic children had no history of wheeze, asthma, allergic sensitization or atopic dermatitis. Preschool asthma was defined as having ≥3 episodes of bronchial obstruction between 2 and 3 years, plus doctor diagnosed asthma and/or asthma medication use by 3 years. The upper limit of normal (ULN) of EDN was defined as the 95th percentile. With Youden Index we calculated EDN cut-off levels for risk of preschool asthma. RESULTS: The overall median (ULN) EDN levels were 27.4 (121) µg/L at 1 year (n = 787), and 20.1 (87.8) µg/L at 3 years (n = 857). Non-atopic children had EDN levels of 24.0 (107) µg/L at 1 year (n = 147), and 17.3 (84.6) µg/L at 3 years (n = 173). EDN levels were higher in boys compared to girls; 32.0 (133) versus 24.5 (97.0) µg/L at 1 year, and 20.9 (96.3) versus 19.0 (72.4) µg/L at 3 years. Preschool asthma was observed in 109/892 (12.2%) children. Higher EDN levels at 1 (>26.7 µg/L) and 3 (≥20.5 µg/L) years were associated with preschool asthma; adjusted OR (95% CI) 2.20 (1.09, 4.41) and 4.68 (2.29, 9.55), respectively. CONCLUSION AND CLINICAL RELEVANCE: We report EDN values in early childhood, demonstrating higher levels at 1 compared to 3 years and in boys compared to girls at both ages. Higher EDN levels at both ages were associated with preschool asthma. However, EDN cut-off levels for preschool asthma were overall lower than the ULN of non-atopic children, limiting translation into clinical practice.
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Asma , Dermatite Atópica , Masculino , Criança , Feminino , Pré-Escolar , Humanos , Neurotoxina Derivada de Eosinófilo , Eosinófilos , Biomarcadores , Asma/diagnóstico , Asma/epidemiologia , Asma/etiologiaRESUMO
BACKGROUND: Blood drawings is a common hospital procedure involving laboratory and clinical disciplines that is important for the diagnosis and management of illnesses in children. Blood drawings with pre-analytical error (PAE) can lead to increased costs for hospitals and healthcare organisations. The direct cost of blood drawings after a PAE is not fully understood in paediatric hospital care. AIM: The aim of this study was to estimate the average direct cost of PAE per year and per 10,000 blood drawings in tertiary paediatric care. METHODS: A cost analysis using a bottom-up approach was conducted on the basis of combined information from the hospital's laboratory register for the period 2013-2014 and clinical in-ward observations at a tertiary children's referral hospital in Sweden, the Astrid Lindgren Children's Hospital. For the analysis, we hypothesised the re-collection of all blood drawings with PAE and included the average costs of the sampling materials, the time of the healthcare personnel, the laboratory analyses, and in-ward premises based on the time spent on the blood sampling procedure. RESULTS: The annual cost of PAE was estimated to be 74,267 euros per 54,040 blood drawings, which corresponds to 13,756 euros per 10,000 blood drawings or 1.5 euros per draw. The personnel cost represented 60.1% (45,261 euros per year) of the cost due to PAE, followed by costs for hospitalisation (25.2%), laboratory analyses (8.1%), and materials (5.7%). CONCLUSION: PAEs lead to substantial increases in the costs in tertiary paediatric hospital care. If these PAEs can be avoided, costs related to the re-collection of blood drawings with PAE may be re-allocated to other health-promoting activities for children visiting hospital institutions.
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Hospitais Pediátricos , Lepidópteros , Humanos , Criança , Animais , Custos e Análise de Custo , Instalações de Saúde , Pessoal de Saúde , HospitalizaçãoRESUMO
AIMS AND OBJECTIVES: The primary aim was to explore whether infants with pain symptoms (colic, abdominal pain and visit to healthcare provider with pain or other discomforts) had increased multimorbidity (common infections, eczema and food sensitivity) compared with infants without these conditions. Secondarily, we aimed to determine whether infant pain symptoms were associated with maternal perceived stress in pregnancy and 3 months postpartum. BACKGROUND: Infant colic and abdominal pain are common concerns in early infancy. Nevertheless, to our knowledge, little research exists on the relationship between infant pain and common infant infections, eczema and food sensitization as comorbidities, and the impact of infant pain on the development of maternal perceived stress from pregnancy to infancy is inconsistent. DESIGN: This study was cross-sectional and partly prospective. METHODS: The sample consisted of mother-infant pairs (N = 1852); information regarding infant pain and multimorbidity was collected from the 3-month questionnaire and postpartum visits in the PreventADALL prospective cohort study. Chi-square tests and regression analyses were conducted. The STROBE checklist was followed. RESULTS: Our results showed a statistically significant higher proportion of respiratory and other infections in infants with pain symptoms. The odds of infant pain were higher for infants with multimorbidity compared to those with no comorbidity. Mothers of infants with colic and of infants visiting healthcare with pain and other discomforts reported statistically significant higher perceived stress by 3 months compared with mothers of infants with no reported pain. CONCLUSION: Our results indicate an association between infant pain symptoms and the presence of infections. Mothers of infants with colic and visiting healthcare had higher perceived stress compared to the no pain group. IMPLICATIONS FOR PRACTICE: Our study indicates that infant pain is associated with infant multimorbidity and maternal perceived stress, which may be useful when planning diagnostic, treatment and coping strategies in infant and family care. PATIENT OR PUBLIC CONTRIBUTION: The PreventADALL is a collaborative study with governmental and patient organisation representation. Selected infants with parents were also contributing during calibrating courses on eczema assessment for the data collectors. TRIAL REGISTRATION: The study was approved by the Regional Committee in Norway (2014/518) and Sweden (2014/2242-31/4) and registered at clinicaltrial.gov (NCT02449850). Link for clinical trials: https://clinicaltrials.gov/ct2/show/NCT02449850.
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Cólica , Eczema , Feminino , Gravidez , Lactente , Humanos , Cólica/epidemiologia , Estudos Prospectivos , Estudos de Coortes , Multimorbidade , Estudos Transversais , Período Pós-Parto , Mães , Dor Abdominal , Estresse PsicológicoRESUMO
Background: Athletes are at risk for developing exercise-induced lower airway narrowing. The diagnostic assessment of such lower airway dysfunction (LAD) requires an objective bronchial provocation test (BPT). Objectives: Our primary aim was to assess if unsupervised field-based exercise challenge tests (ECTs) could confirm LAD by using app-based spirometry. We also aimed to evaluate the diagnostic test performance of field-based and sport-specific ECTs, compared with established eucapnic voluntary hyperpnoea (EVH) and methacholine BPT. Methods: In athletes with LAD symptoms, sensitivity and specificity analyses were performed to compare outcomes of (1) standardised field-based 8 min ECT at 85% maximal heart rate with forced expiratory volume in 1 s (FEV1) measured prechallenge and 1 min, 3 min, 5 min, 10 min, 15 min and 30 min postchallenge, (2) unstandardised field-based sport-specific ECT with FEV1 measured prechallenge and within 10 min postchallenge, (3) EVH and (4) methacholine BPT. Results: Of 60 athletes (median age 17.5; range 16-28 years.; 40% females), 67% performed winter-sports, 43% reported asthma diagnosis. At least one positive BPT was observed in 68% (n=41/60), with rates of 51% (n=21/41) for standardised ECT, 49% (n=20/41) for unstandardised ECT, 32% (n=13/41) for EVH and methacholine BPT, while both standardised and unstandardised ECTs were simultaneously positive in only 20% (n=7/35). Standardised and unstandardised ECTs confirmed LAD with 54% sensitivity and 70% specificity, and 46% sensitivity and 68% specificity, respectively, using EVH as a reference, while EVH and methacholine BPT were both 33% sensitive and 85% specific, using standardised ECTs as reference. Conclusion: App-based spirometry for unsupervised field-based ECTs may support the diagnostic process in athletes with LAD symptoms. Trial registration number: NCT04275648.
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BACKGROUND: Breastmik is considered the optimal source of nutrition in early infancy. However, recommendations and practices for when and how complementary food should be introduced in the first year of life vary worldwide. Early introduction of allergenic foods may prevent food allergies, but if early food introduction influences infant feeding practices is less known. OBJECTIVES: We sought to assess infant feeding practices in the first year of life and to determine if early interventional food introduction influences breastfeeding and dietary diversity. METHODS: Dietary intake was assessed in infants from the population-based clinical trial Preventing Atopic Dermatitis and ALLergies (PreventADALL) in children study. A total of 2397 infants were cluster-randomized at birth into 4 different groups: 1) control, 2) skin intervention, 3) introduction to 4 allergenic foods between 3 and 4 mo of age: peanut, cow milk, wheat, and egg, as small tastings until 6 mo, and 4) combined skin and food interventions. Dietary data were available from at least one of the 3-, 6-, 9-, and 12-mo questionnaires in 2059 infants. In the present analysis, groups 1 and 2 constitute the No Food Intervention group, whereas groups 3 and 4 constitute the Food Intervention group. We used the log-rank test and Cox regression to assess the impact of food intervention on age of breastfeeding cessation. Mixed effects logistic regression was used to compare dietary diversity, defined as the number of food categories consumed, between intervention groups. RESULTS: At 3, 6, 9, and 12 mo, 95%, 88%, 67%, and 51% were breastfed, respectively, and breastfeeding duration was not affected by the food intervention. In the No Food Intervention group, mean age of complementary food introduction was 18.3 wk (confidence interval [CI]: 18.1, 18.5). In the Food Intervention group, the dietary diversity score was 1.39 units (CI: 1.16, 1.62) higher at 9 mo (P < 0.001) and 0.7 units (CI: 0.5, 0.9) higher at 12 mo (P < 0.001) compared to the No Food Intervention group. CONCLUSIONS: Early food intervention did not affect breastfeeding rates and increased dietary diversity at 9 and 12 mo.
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Dieta Saudável , Hipersensibilidade Alimentar , Feminino , Lactente , Estudos de Coortes , Hipersensibilidade Alimentar/prevenção & controle , Fenômenos Fisiológicos da Nutrição do Lactente , Humanos , Leite , Aleitamento Materno , Alimentação com Mamadeira , Recém-NascidoRESUMO
Bacteroides and Phocaeicola, members of the family Bacteroidaceae, are among the first microbes to colonize the human infant gut. While it is known that these microbes can be transmitted from mother to child, our understanding of the specific strains that are shared and potentially transmitted is limited. In this study, we aimed to investigate the shared strains of Bacteroides and Phocaeicola in mothers and their infants. We analyzed fecal samples from pregnant woman recruited at 18 weeks of gestation from the PreventADALL study, as well as offspring samples from early infancy, including skin swab samples taken within 10 min after birth, the first available fecal sample (meconium), and fecal samples at 3 months of age. We screened 464 meconium samples for Bacteroidaceae, with subsequent selection of 144 mother-child pairs for longitudinal analysis, based on the presence of Bacteroidaceae, longitudinal sample availability, and delivery mode. Our results showed that Bacteroidaceae members were mainly detected in samples from vaginally delivered infants. We identified high prevalences of Phocaeicola vulgatus, Phocaeicola dorei, Bacteroides caccae, and Bacteroides thetaiotaomicron in mothers and vaginally born infants. However, at the strain level, we observed high prevalences of only two strains: a B. caccae strain and a P. vulgatus strain. Notably, the B. caccae strain was identified as a novel component of mother-child shared strains, and its high prevalence was also observed in publicly available metagenomes worldwide. Our findings suggest that mode of delivery may play a role in shaping the early colonization of the infant gut microbiota, in particular the colonization of Bacteroidaceae members. IMPORTANCE Our study provides evidence that Bacteroidaceae strains present on infants' skin within 10 min after birth, in meconium samples, and in fecal samples at 3 months of age in vaginally delivered infants are shared with their mothers. Using strain resolution analyses, we identified two strains, belonging to Bacteroides caccae and Phocaeicola vulgatus, as shared between mothers and their infants. Interestingly, the B. caccae strain showed a high prevalence worldwide, while the P. vulgatus strain was less common. Our findings also showed that vaginal delivery was associated with early colonization of Bacteroidaceae members, whereas cesarean section delivery was associated with delayed colonization. Given the potential for these microbes to influence the colonic environment, our results suggest that understanding the bacterial-host relationship at the strain level may have implications for infant health and development later in life.
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Bacteroidaceae , Cesárea , Lactente , Humanos , Feminino , Gravidez , Transmissão Vertical de Doenças Infecciosas , Bacteroides/genética , Fezes , Relações Mãe-FilhoAssuntos
Asma , Receptores de Calcitriol , Humanos , Criança , Receptores de Calcitriol/genética , Suécia/epidemiologia , Vitamina D , Predisposição Genética para Doença , Asma/epidemiologia , Asma/genética , Instituições Acadêmicas , Polimorfismo de Nucleotídeo Único , Proteína de Ligação a Vitamina D/genéticaRESUMO
BACKGROUND: Reduced lung function at birth has evident antenatal origins and is associated with an increased risk of wheezing and asthma later in life. Little is known about whether blood flow in the fetal pulmonary artery, may impact postnatal lung function. OBJECTIVE: Our primary aim was to investigate the potential associations between fetal Doppler blood flow velocity measures in the fetal branch pulmonary artery, and infant lung function by tidal flow-volume (TFV) loops at three months of age in a low-risk population. Our secondary aim was to explore the association between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries, and the same lung function measures. METHODS: In 256 non-selected pregnancies from the birth cohort study Preventing Atopic Dermatitis and ALLergies in Children (PreventADALL) we performed fetal ultrasound examination with Doppler blood flow velocity measurements at 30 gestational weeks (GW). We recorded the pulsatility index, peak systolic velocity, time-averaged maximum velocity, acceleration time/ejection time ratio, and time velocity integral primarily in the proximal pulmonary artery close to the pulmonary bifurcation. The pulsatility index was measured in the umbilical and middle cerebral arteries and the peak systolic velocity in the middle cerebral artery. The cerebro-placental ratio (ratio between pulsatility index in the middle cerebral and umbilical arteries) was calculated. Infant lung function was assessed using TFV loops in awake, calmly breathing three months old infants. The outcome was the time to peak tidal expiratory flow to expiratory time ratio (tPTEF/tE), tPTEF/tE <25th percentile, and tidal volume per kg body weight (VT/kg). Potential associations between fetal Doppler blood flow velocity measures and infant lung function were assessed using linear and logistic regressions. RESULTS: The infants were born at median (min - max) 40.3 (35.6 - 42.4) GW, with a mean (SD) birth weight of 3.52 (0.46) kg, and 49.4% were females. The mean (SD) tPTEF/tE was 0.39 (0.1) and the 25th percentile was 0.33. Neither univariable nor multivariable regression models revealed any associations between fetal pulmonary blood flow velocity measures and tPTEF/tE, tPTEF/tE <25th percentile, or VT/kg at three months of age. Similarly, we did not observe associations between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries and infant lung function measures. CONCLUSION: In a cohort of 256 infants from the general population, fetal third-trimester Doppler blood flow velocity measures in the branch pulmonary, umbilical, and middle cerebral arteries were not associated with infant lung function measures at three months of age.
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Placenta , Artéria Pulmonar , Recém-Nascido , Criança , Lactente , Humanos , Gravidez , Feminino , Masculino , Artéria Pulmonar/diagnóstico por imagem , Estudos de Coortes , Velocidade do Fluxo Sanguíneo/fisiologia , Estudos Prospectivos , Pulmão/diagnóstico por imagem , Ultrassonografia Doppler , Artérias Umbilicais/fisiologia , Ultrassonografia Pré-NatalRESUMO
Rationale: Children with preschool wheezing or school-age asthma are reported to have airway microbial imbalances. Objectives: To identify clusters in children with asthma or wheezing using oropharyngeal microbiota profiles. Methods: Oropharyngeal swabs from the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) pediatric asthma or wheezing cohort were characterized using 16S ribosomal RNA gene sequencing, and unsupervised hierarchical clustering was performed on the Bray-Curtis ß-diversity. Enrichment scores of the Molecular Signatures Database hallmark gene sets were computed from the blood transcriptome using gene set variation analysis. Children with severe asthma or severe wheezing were followed up for 12-18 months, with assessment of the frequency of exacerbations. Measurements and Main Results: Oropharyngeal samples from 241 children (age range, 1-17 years; 40% female) revealed four taxa-driven clusters dominated by Streptococcus, Veillonella, Rothia, and Haemophilus. The clusters showed significant differences in atopic dermatitis, grass pollen sensitization, FEV1% predicted after salbutamol, and annual asthma exacerbation frequency during follow-up. The Veillonella cluster was the most allergic and included the highest percentage of children with two or more exacerbations per year during follow-up. The oropharyngeal clusters were different in the enrichment scores of TGF-ß (transforming growth factor-ß) (highest in the Veillonella cluster) and Wnt/ß-catenin signaling (highest in the Haemophilus cluster) transcriptomic pathways in blood (all q values <0.05). Conclusions: Analysis of the oropharyngeal microbiota of children with asthma or wheezing identified four clusters with distinct clinical characteristics (phenotypes) that associate with risk for exacerbation and transcriptomic pathways involved in airway remodeling. This suggests that further exploration of the oropharyngeal microbiota may lead to novel pathophysiologic insights and potentially new treatment approaches.
Assuntos
Asma , Hipersensibilidade , Microbiota , Feminino , Masculino , Humanos , Transcriptoma , Sons Respiratórios/genética , Asma/genética , Microbiota/genéticaRESUMO
BACKGROUND: We aimed to investigate the relationship between fetal third trimester lung volume (LV), thoracic circumference (TC), fetal weight, as well as fetal thoracic and weight growth, and early infant lung function. METHODS: Fetal LV, TC and estimated weight were measured with ultrasound at 30 gestational weeks in 257 fetuses from the general population-based prospective cohort study Preventing Atopic Dermatitis and ALLergies in Children (PreventADALL). Fetal thoracic growth rate and weight increase were calculated using TC and estimated fetal weight measured by ultrasound during pregnancy, and TC and birthweight of the newborn. Lung function was assessed by tidal flow-volume measurement in awake infants at 3 months of age. The associations between fetal size (LV, TC, and estimated weight) and growth (thoracic growth rate and fetal weight increase) measures and the time to peak tidal expiratory flow to expiratory time ratio (tPTEF /tE ) as well as tidal volume standardized for body weight (VT /kg) were analyzed using linear and logistic regression models. RESULTS: We observed no associations between fetal LV, TC or estimated fetal weight and tPTEF /tE as a continuous variable, tPTEF /tE < 25th percentile, or VT /kg. Similarly, fetal thoracic growth and weight increase were not associated with infant lung function. Analyses stratified for sex showed a significant inverse association between fetal weight increase and VT /kg (p = 0.02) in girls. CONCLUSION: Overall, fetal third trimester LV, TC, estimated fetal weight, thoracic growth rate and weight increase were not associated with infant lung function at 3 months of age.
Assuntos
Peso Fetal , Pulmão , Recém-Nascido , Gravidez , Criança , Feminino , Humanos , Lactente , Terceiro Trimestre da Gravidez , Estudos Prospectivos , Volume de Ventilação Pulmonar , Pulmão/diagnóstico por imagem , Feto , Ultrassonografia Pré-NatalRESUMO
BACKGROUND: Early-life microbial colonization of the skin may modulate the immune system and impact the development of atopic dermatitis (AD) and allergic diseases later in life. To address this question, we assessed the association between the skin microbiome and AD, skin barrier integrity and allergic diseases in the first year of life. We further explored the evolution of the skin microbiome with age and its possible determinants, including delivery mode. METHODS: Skin microbiome was sampled from the lateral upper arm on the first day of life, and at 3, 6, and 12 months of age. Bacterial communities were assessed by 16S rRNA gene amplicon sequencing in 346 infants from the PreventADALL population-based birth cohort study, representing 970 samples. Clinical investigations included skin examination and skin barrier function measured as trans-epidermal water loss (TEWL) at the site and time of microbiome sampling at 3, 6, and 12 months. Parental background information was recorded in electronic questionnaires, and delivery mode (including vaginal delivery (VD), VD in water, elective caesarean section (CS) and emergency CS) was obtained from maternal hospital charts. RESULTS: Strong temporal variations in skin bacterial community composition were found in the first year of life, with distinct patterns associated with different ages. Confirming our hypothesis, skin bacterial community composition in the first year of life was associated with skin barrier integrity and later onsets of AD. Delivery mode had a strong impact on the microbiome composition at birth, with each mode leading to distinct patterns of colonization. Other possible determinants of the skin microbiome were identified, including environmental and parental factors as well as breastfeeding. CONCLUSION: Skin microbiome composition during infancy is defined by age, transiently influenced by delivery mode as well as environmental, parental factors and breastfeeding. The microbiome is also associated with skin barrier integrity and the onset of AD.