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BACKGROUND: An important window of opportunity for early-life exposures has been proposed for the development of atopic eczema and asthma.OBJECTIVE: However, it is unknown whether hay fever with a peak incidence around late school age to adolescence is similarly determined very early in life.METHODS: In the Protection against Allergy-Study in Rural Environments (PASTURE) birth cohort potentially relevant exposures such as farm milk consumption and exposure to animal sheds were assessed at multiple time points from infancy to age 10.5 years and classified by repeated measure latent class analyses (n [ 769). Fecal samples at ages 2 and 12 months were sequenced by 16S rRNA. Hay fever was defined by parent -reported symptoms and/or physician's diagnosis of hay fever in the last 12 months using questionnaires at 10.5 years.RESULTS: Farm children had half the risk of hay fever at 10.5 years (adjusted odds ratio [aOR] 0.50; 95% CI 0.31-0.79) than that of nonfarm children. Whereas early life events such as gut microbiome richness at 12 months (aOR 0.66; 95% CI 0.46-0.96) and exposure to animal sheds in the first 3 years of life (aOR 0.26; 95% CI 0.06-1.15) were determinants of hay fever, the continuous consumption of farm milk from infancy up to school age was necessary to exert the protective effect (aOR 0.35; 95% CI 0.17-0.72).CONCLUSIONS: While early life events determine the risk of subsequent hay fever, continuous exposure is necessary to achieve protection. These findings argue against the notion that only early life exposures set long-lasting trajectories. (c) 2022 The Authors. Published by Elsevier Inc

Background The primary aim was to evaluate the association between gestational diabetes and blood glucose levels and vulvovaginal yeast infections in pregnancy. Secondly, we clarified the possible associations between maternal and prenatal factors, and birth outcomes and yeast infections. Methods Three thousand nine hundred sixty-five pregnant women of the Kuopio Birth Cohort Study (KuBiCo) reported vulvovaginal yeast infections during pregnancy, via electronic questionnaires. Maternal and prenatal data, as well as clinical obstetric and early neonatal outcomes were registered during and after birth. The oral glucose tolerance test was performed on 3,079 women during pregnancy. Logistic regression analysis evaluated the possible multivariable associations between yeast infections, gestational diabetes and other prenatal and maternal factors. Results No association was detected between gestational diabetes or blood glucose levels and vulvovaginal yeast infections during pregnancy. In multivariable analysis, women with yeast infections were more often multiparous, with higher education and had used more often antibiotics during pregnancy compared to others. No significant associations were detected in multivariable analysis between infections, the mode of delivery, preterm birth, birth weight or Apgar scores. Conclusions Women with reported vulvovaginal yeast infections managed generally well during pregnancy. They had no more gestational diabetes or higher blood glucose levels and their newborns managed equally well during early neonatal period.

Background and Aims Moisture damage increases the risk for respiratory disorders in childhood. Our aim was to determine whether early age residential exposure to inspector-observed moisture damage or mold is associated with different wheezing phenotypes later in childhood. Methods Building inspections were performed by civil engineers, in a standardized manner, in the children's homes-mostly single family and row houses (N = 344)-in the first year of life. The children were followed up with repeated questionnaires until the age of 6 years and wheezing phenotypes-never/infrequent, transient, intermediate, late onset, and persistent-were defined using latent class analyses. The multinomial logistic regression model was used for statistical analysis. Results A total of 63% (n = 218) had infrequent or no wheeze, 23% (n = 80) had transient and 9.6% (n = 21) had a persistent wheeze. Due to the low prevalence, results for intermediate (3.8%, n = 13) and late-onset wheeze (3.5%, n = 12) were not further evaluated. Most consistent associations were observed with the persistent wheeze phenotype with an adjusted odds ratio (95% confidence intervals) 2.04 (0.67-6.18) for minor moisture damage with or without mold spots (present in 23.8% of homes) and 3.68 (1.04-13.05) for major damage or any moisture damage with visible mold in a child's main living areas (present in 13.4% of homes). Early-age moisture damage or mold in the kitchen was associated with transient wheezing. Conclusion At an early age, residential exposure to moisture damage or mold, can be dose-dependently associated especially with persistent wheezing phenotype later in childhood.

Background Exposure to indoor moisture damage and visible mold has been found to be associated with asthma and respiratory symptoms in several questionnaire-based studies by self-report. We aimed to define the prospective association between the early life exposure to residential moisture damage or mold and fractional exhaled nitric oxide (FeNO) and lung function parameters as objective markers for airway inflammation and asthma in 6-year-old children. Methods Home inspections were performed in children's homes when infants were on average 5 months old. At age 6 years, data on FeNO (n = 322) as well as lung function (n = 216) measurements were collected. Logistic regression and generalized additive models were used for statistical analyses. Results Early age major moisture damage and moisture damage or mold in the child's main living areas were significantly associated with increased FeNO levels (>75th percentile) at the age of 6 years (adjusted odds ratios, 95% confidence intervals, aOR (95% CI): 3.10 (1.35-7.07) and 3.16 (1.43-6.98), respectively. Effects were more pronounced in those who did not change residential address throughout the study period. For lung function, major structural damage within the whole home was associated with reduced FEV1 and FVC, but not with FEV1/FVC. No association with lung function was observed with early moisture damage or mold in the child's main living areas. Conclusion These results underline the importance of prevention and remediation efforts of moisture and mold-damaged buildings in order to avoid harmful effects within the vulnerable phase of the infants and children's immunologic development.

BACKGROUND: Allergies are a serious public health issue, and prevalences are rising worldwide. The role of antibiotics in the development of allergies has repeatedly been discussed, as results remain inconsistent. The aim of this study was to investigate the association between pre- and post-natal antibiotic exposure and subsequent development of allergies (atopic dermatitis, food allergy, asthma, atopic sensitization and allergic rhinitis). METHODS: A total of 1080 children who participated in a European birth cohort study (PASTURE) were included in this analysis. Data on antibiotic exposure during pregnancy and/or first year of life and allergic diseases were collected by questionnaires from pregnancy up to 6 years of age and analysed by performing logistic regressions. To take into account reverse causation, we included models, where children with diagnosis or symptoms of the respective disease in the first year of life were excluded. RESULTS: Antibiotic exposure in utero was significantly and positively associated with atopic dermatitis and food allergy. The strongest effect was on diseases with onset within the first year of life (for atopic dermatitis: aOR 1.66, 95% CI 1.11-2.48 and for food allergy: aOR 3.01, 95% CI 1.22-7.47). Antibiotics in the first year of life were positively associated with atopic dermatitis up to 4 years (aOR 2.73, 95% CI 1.66-4.49) and also suggested a dose-response relationship. A tendency was observed with asthma between 3 and 6 years (aOR 1.65, 95% CI 0.95-2.86). CONCLUSIONS: Our findings show positive associations between exposure to antibiotics and allergies, mainly atopic dermatitis and food allergy within the first year of life, after prenatal exposure, and atopic dermatitis and asthma after post-natal exposure to antibiotics in children born in rural settings.

Background Microbial exposures in early childhood direct the development of the immune system and their diversity may influence the risk of allergy development. We aimed to determine whether the indoor microbial diversity at early-life is associated with the development of allergic rhinitis and inhalant atopy. Methods The study population included children within two birth cohorts: Finnish rural-suburban LUKAS (N = 312), and German urban LISA from Munich and Leipzig study centers (N = 248). The indoor microbiota diversity (Chao1 richness and Shannon entropy) was characterized from floor dust samples collected at the child age of 2–3 months by Illumina MiSeq sequencing of bacterial and fungal DNA amplicons. Allergic rhinitis and inhalant atopy were determined at the age of 10 years and analyzed using logistic regression models. Results High bacterial richness (aOR 0.19, 95%CI 0.09–0.42 for middle and aOR 0.12, 95%CI 0.05–0.29 for highest vs. lowest tertile) and Shannon entropy were associated with lower risk of allergic rhinitis in LISA, and similar trend was seen in LUKAS. We observed some significant associations between bacterial and fungal diversity measured and the risk of inhalant atopy, but the associations were inconsistent between the two cohorts. High bacterial diversity tended to be associated with increased risk of inhalant atopy in rural areas, but lower risk in more urban areas. Fungal diversity tended to be associated with increased risk of inhalant atopy only in LISA. Conclusions Our study suggests that a higher bacterial diversity may reduce the risk of allergic rhinitis later in childhood. The environment-dependent heterogeneity in the associations with inhalant atopy – visible here as inconsistent results between two differing cohorts - suggests that specific constituents of the diversity may be relevant.

Polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are persistent organic pollutants that have detrimental health effects. As people are exposed to them mainly through the diet, EU has set maximum food dioxin and PCBs levels. EFSA CONTAM Panel made new risk assessment in 2018 that lowered the tolerable weekly intake (TWI) from 14 pg-TEQ/kg bw/week to 2 pgTEQ/kg bw/week. Critical effect was decreased semen count at the age of 18-19 years if serum total TEQ at the age of 9 years exceeded the No Observed Adverse Effect Level (NOAEL) of 7 pg/g lipid. However, it is largely unknown to what extent NOAEL is exceed in European boys currently. We thus measured PCBs from small volume of serum in 184 Finnish children 7-10 years of age. To estimate the TEQ levels of children from measured PCB levels, we used our existing human milk PCDD/F and PCB concentrations to create a hierarchical Bayesian regression model that was used to estimate TEQs from measured PCBs. For quality control (QC), three pooled blood samples from 18 to 20 year old males were measured for PCDD/Fs and PCBs, and estimated for TEQs. In QC samples measured and estimated TEQs agreed within 84% -106%. In our estimate for 7-10 year old children, PCDD/F TEQ exceeded NOAEL only in 0.5% and total TEQ in 2.7% of subjects. Risk management following the decreased TWI proposed by the CONTAM Panel should be carefully considered if total TEQ in children is already largely below the NOAEL. (C) 2020 Elsevier Ltd. All rights reserved.

Background Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. Methods and findings We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers’ median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02–1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02–1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07–2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35–1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52–2.34] instead of OR 2.20 [95% CI 2.02–2.42] when reducing from 5–9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39–3.25] and OR 1.93 [95% CI 1.46–2.57] instead of OR 2.95 [95% CI 2.75–3.15] when reducing from ≥10 to 5–9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16–1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations. Conclusions We observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy., Elise Philips and co-workers investigate parental smoking and associated birth and child outcomes., Author summary Why was this study done? Maternal smoking during pregnancy is an important risk factor for various birth complications and childhood overweight. It is not clear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy. The associations of paternal smoking with birth and childhood outcomes also remain unknown. What did the researchers do and find? We conducted an individual participant data meta-analysis using data from 229,158 families from 28 pregnancy and birth cohorts from Europe and North America to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. We observed that smoking in the first trimester only did not increase the risk of preterm birth and small size for gestational age but was associated with a higher risk of childhood overweight, as compared to nonsmoking. Reducing the number of cigarettes during pregnancy, without quitting, was still associated with higher risks of these adverse outcomes. Paternal smoking seems to be associated, independently of maternal smoking, with the risks of childhood overweight. What do these findings mean? Population strategies should focus on parental smoking prevention before or at the start of, rather than during, pregnancy. Future studies are needed to assess the specific associations of smoking in the preconception and childhood periods with offspring outcomes.

International audience; Background The effect of exposure to micro-organisms on allergic diseases has been well studied. The protective effect of early food diversity against allergic diseases was previously shown in the PASTURE cohort study. The consumption of cheese, a food potentially rich in microbial diversity, deserves further examination. We aimed to evaluate whether cheese consumption is associated with allergic diseases. Methods In the PASTURE study (birth cohort in 5 European countries), data on feeding practices, environmental factors and allergic diseases were collected by questionnaires from birth to 6 years (N=931). Cheese consumption at 18 months of age was quantified in terms of frequency and diversity (i.e., number of consumed types among 6 types: hard pressed, semi-pressed, soft, blue, fresh cheese, from the farm). Multiple logistic regressions were performed to evaluate the effect of cheese consumption on atopic dermatitis (AD), food allergy (FA), allergic rhinitis, asthma and atopic sensitization at 6 years after adjustment for confounders of atopy. Results Cheese consumption (vs. non-consumption) had a significant protective effect on AD (OR=0.51 [0.29-0.90], p=0.02) and FA (OR=0.32, [0.15-0.71], p=0.004), but no effect on atopic sensitization, allergic rhinitis and asthma at 6 years. This effect on AD and FA may be related to the diversity of consumed cheeses (OR=0.64 [0.48-0.85] per cheese type, p=0.002; OR=0.55 [0.33-0.92], p=0.02, respectively). Conclusions Although reverse causality cannot totally be ruled out, cheese diversity at 18 months had a protective effect against AD and FA at 6 years in addition to the protective effect of diversity of other foods.

There is no commonly approved approach to detect and quantify the health-relevant microbial exposure in moisture-damaged buildings. In 39 single-family homes with severe moisture damage, we studied whether concentrations of viable microbes in building material samples are associated with health among 71 adults and 68 children, and assessed with symptoms questionnaires, exhaled NO, and peak expiratory flow (PEF) variability. Symptoms were grouped into three scores: upper respiratory symptoms, lower respiratory symptoms, and general symptoms. The homes were divided into three groups based on viable counts of fungi, actinomycetes, and total bacteria cultivated from building material samples. Highest group of actinomycete counts was associated with more general symptoms, worse perceived health, and higher daily PEF variability (aOR 12.51; 1.10-141.90 as compared to the lowest group) among adults, and with an increase in lower respiratory symptoms in children, but the confidence intervals were wide. We observed significant associations of fungal counts and total microbial score with worse perceived health in adults. No associations with exhaled NO were observed.

Background: Early-life indoor bacterial exposure is associated with the risk of asthma, but the roles of specific bacterial genera are poorly understood. Objective: We sought to determine whether individual bacterial genera in indoor microbiota predict the development of asthma. Methods: Dust samples from living rooms were collected at 2 months of age. The dust microbiota was characterized by using Illumina MiSeq sequencing amplicons of the bacterial 16S ribosomal RNA gene. Children (n = 373) were followed up for ever asthma until the age of 10.5 years. Results: Richness was inversely associated with asthma after adjustments (P = .03). The phylogenetic microbiota composition in asthmatics patients' homes was characteristically different from that in nonasthmatic subjects' homes (P = .02, weighted UniFrac, adjusted association, permutational multivariate analysis of variance, PERMANOVA-S). The first 2 axis scores of principal coordinate analysis of the weighted UniFrac distance matrix were inversely associated with asthma. Of 658 genera detected in the dust samples, the relative abundances of 41 genera correlated (r > vertical bar 0.4 vertical bar) with one of these axes. Lactococcus genus was a risk factor for asthma (adjusted odds ratio, 1.36 [95% CI, 1.13-1.63] per interquartile range change). The abundance of 12 bacterial genera (mostly from the Actinomycetales order) was associated with lower asthma risk (P

Background and objective The farm environment, especially contact with farm animals in early childhood, may prevent allergic sensitization during adulthood. However, prospective associations between exposure to the farm environment and polysensitization have not been studied. Polysensitization is a risk factor for asthma and asthma-related morbidity. Objective: To investigate whether exposure to a farming environment in early childhood, especially exposure to animals, is associated with sensitization to specific allergens and polysensitization at the age of 31. Methods In a prospective birth cohort study, 5509 individuals born in northern Finland in 1966 underwent skin prick testing against birch, timothy, cat, and house dust mite at the age of 31. Prenatal exposure to the farming environment was documented at birth, whereas information on childhood exposure to pets was only collected retrospectively at the age of 31. Data were analyzed using logistic regression. Results Being born to a family with farm animals was associated with a reduced risk of sensitization to birch, timothy, and cat (adjusted odds ratio [aOR], 0.55 [95%CI, 0.43-0.70]; aOR, 0.62 [95%CI, 0.48-0.79]; aOR, 0.60 [95%CI, 0.47-0.75]) and polysensitization at the age of 31 (aOR, 0.62 [95%CI, 0.48-0.80]). The number of animal species present during childhood was dose-dependently associated with a reduced risk of sensitization to birch, timothy, and cat, as well as of polysensitization. No association was found with sensitization to house dust mite. Conclusions Growing up on a farm and contact with higher numbers of animal species in childhood are associated with less frequent sensitization to birch, timothy, and cat allergens and polysensitization in adulthood, but not with sensitization to house dust mite.

Growing up on a farm is associated with an asthma-protective effect, but the mechanisms underlying this effect are largely unknown. In the Protection against Allergy: Study in Rural Environments (PASTURE) birth cohort, we modeled maturation using 16S rRNA sequence data of the human gut microbiome in infants from 2 to 12 months of age. The estimated microbiome age (EMA) in 12-month-old infants was associated with previous farm exposure (beta = 0.27 (0.12-0.43), P = 0.001, n = 618) and reduced risk of asthma at school age (odds ratio (OR) = 0.72 (0.56-0.93), P = 0.011). EMA mediated the protective farm effect by 19%. In a nested case-control sample (n = 138), we found inverse associations of asthma with the measured level of fecal butyrate (OR = 0.28 (0.09-0.91), P = 0.034), bacterial taxa that predict butyrate production (OR = 0.38 (0.17-0.84), P = 0.017) and the relative abundance of the gene encoding butyryl-coenzyme A (CoA):acetate-CoA-transferase, a major enzyme in butyrate metabolism (OR = 0.43 (0.19-0.97), P = 0.042). The gut microbiome may contribute to asthma protection through metabolites, supporting the concept of a gut-lung axis in humans.Growing up in the rich microbial environment of a farm strongly influences the maturation of the gut microbiome in the first year of life, which helps protect against the development of asthma in children.

Asthma prevalence has increased in epidemic proportions with urbanization, but growing up on traditional farms offers protection even today1. The asthma-protective effect of farms appears to be associated with rich home dust microbiota2,3, which could be used to model a health-promoting indoor microbiome. Here we show by modeling differences in house dust microbiota composition between farm and non-farm homes of Finnish birth cohorts4 that in children who grow up in non-farm homes, asthma risk decreases as the similarity of their home bacterial microbiota composition to that of farm homes increases. The protective microbiota had a low abundance of Streptococcaceae relative to outdoor-associated bacterial taxa. The protective effect was independent of richness and total bacterial load and was associated with reduced proinflammatory cytokine responses against bacterial cell wall components ex vivo. We were able to reproduce these findings in a study among rural German children2 and showed that children living in German non-farm homes with an indoor microbiota more similar to Finnish farm homes have decreased asthma risk. The indoor dust microbiota composition appears to be a definable, reproducible predictor of asthma risk and a potential modifiable target for asthma prevention. Exposure to a farm-like house dust microbiome is associated with protection against asthma development in children living in urban environments.

This study evaluates the association between indoor microbial diversity early in life and hyperactivity/inattention symptoms in children at ages 10 and 15 years.A random sample enriched with subjects with hyperactivity/inattention at age 15 years was selected from the German LISA birth cohort. Bedroom floor dust was collected at age 3 months and 4 bacterial and fungal diversity measures [number of observed operational taxonomic units (OTUs), Chao1, Shannon and Simpson indices] were calculated from Illumina MiSeq sequencing data. Hyperactivity/inattention was based on the Strengths and Difficulties Questionnaire at ages 10 and 15 (cut-off ≥7). Adjusted associations between 4 diversity measures in tertiles and hyperactivity/inattention were investigated with weighted and survey logistic regression models. We included 226 individuals with information on microbial diversity and hyperactivity/inattention. Early life bacterial diversity was inversely associated with hyperactivity/inattention at age 10 [bacterial OTUs (medium vs low: aOR = 0.4, 95%CI = (0.2–0.8)) and Chao1 (medium vs low: 0.3 (0.1–0.5); high vs low: 0.3 (0.2–0.6)], whereas fungal diversity was directly associated [Chao1 (high vs low: 2.1 (1.1–4.0)), Shannon (medium vs low: 2.8 (1.3–5.8)), and Simpson (medium vs low: 4.7 (2.4–9.3))]. At age 15, only Shannon index was significantly associated with hyperactivity/inattention [bacteria (medium vs low: 2.3 (1.2–4.2); fungi (high vs low: 0.5 (0.3–0.9))]. In conclusion, early life exposure to microbial diversity may play a role in the psychobehavioural development. We observe heterogeneity in the direction of the associations encouraging further longitudinal studies to deepen our understanding of the characteristics of the microbial community underlying the observed associations.

Background: Childhood asthma is often preceded by early wheeze. Usually, wheezing episodes are recorded retrospectively, which may induce recall bias. Aims and objectives: The aim of this study was to investigate true-positive recall of parent-reported wheeze at 1year of age, its determinants, and its implications for asthma and lung function at 6years of age. Methods: The PASTURE (Protection Against Allergy—Study in Rural Environments) study followed 880 children from rural areas in 5 European countries from birth to age 6years. Wheeze symptoms in the first year were asked weekly. At age 6, parent-reported asthma diagnosis was ascertained and lung function measurements were conducted. Correct parental recall of wheeze episodes at the end of the first year was assessed for associations with lung function, asthma, and the asthma risk locus on chromosome 17q21. Results: Parents correctly recalled wheeze after the first year in 54% of wheezers. This true-positive recall was determined by number of episodes, timing of the last wheeze episode, and parental asthma. Independently from these determinants, true-positive recall predicted asthma at age 6years (odds ratio 4.54, 95% confidence interval (CI) [1.75-14.16]) and impaired lung function (β=−0.62, 95% CI [−1.12; −0.13], P-value=.02). Associations were stronger in children with asthma risk SNPs on chromosome 17q21. Conclusion: Correct parental recall of wheezing episodes may reflect clinical relevance of early wheeze and its impact on subsequent asthma and lung function impairment. Questions tailored to parental perception of wheezing episodes may further enhance asthma prediction.

Importance: Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges. Objectives: To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories. Design, setting, and participants: Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample). Optimal gestational weight gain ranges were estimated for each prepregnancy body mass index (BMI) category by selecting the range of gestational weight gain that was associated with lower risk for any adverse outcome. Individual participant-level data from 3505 participants within 4 separate hospital-based cohorts were used as a validation sample. Data were collected between 1989 and 2015. The final date of follow-up was December 2015. Exposures: Gestational weight gain. Main outcomes and measures: The main outcome termed any adverse outcome was defined as the presence of 1 or more of the following outcomes: preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, preterm birth, and small or large size for gestational age at birth. Results: Of the 196 670 women (median age, 30.0 years [quartile 1 and 3, 27.0 and 33.0 years] and 40 937 were white) included in the main sample, 7809 (4.0%) were categorized at baseline as underweight (BMI

Background Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. Methods and findings We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0–5.0 years), mid (5.0–10.0 years) and late childhood (10.0–18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. Conclusions In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy., Vincent Jaddoe and colleagues report that a high BMI before pregnancy, rather than excessive gestational weight gain, is more likely to contribute to childhood obesity., Author summary Why was this study done? Maternal pre-pregnancy obesity and excessive gestational weight gain are important risk factors of various pregnancy and birth complications. An accumulating body of evidence suggests that maternal obesity and excessive gestational weight gain also have persistent effects on offspring fat development. It is not clear whether these effects exist across the full ranges of maternal pre-pregnancy body mass index and gestational weight gain, what their combined effects are, and what the population impact of these effects is. What did the researchers do and find? We conducted an individual participant data meta-analysis using data from 162,129 mothers and their children from 37 pregnancy and birth cohorts from Europe, North America, and Australia to assess the separate and combined associations of maternal pre-pregnancy body mass index and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. We observed not only that maternal pre-pregnancy overweight and obesity were associated with an increased risk of childhood overweight/obesity, but that this risk increased gradually over the full range of maternal BMI. Similarly, the risk of childhood overweight/obesity increased across the full range of gestational weight gain. We estimated that 21.7% to 41.7% of childhood overweight/obesity prevalence could be attributed to maternal overweight and obesity together, whereas 11.4% to 19.2% could be attributed to excessive gestational weight gain. The additional effect of excessive gestational weight gain on the risk of childhood overweight/obesity was small among women who are already overweight or obese before pregnancy. What do these findings mean? Maternal pre-pregnancy BMI and, to a smaller extent, gestational weight gain are important modifiable risk factors of childhood overweight/obesity with considerable population impact. Future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight status during pregnancy.

ObjectiveTo assess the separate and combined associations of maternal pre‐pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact.DesignIndividual participant data meta‐analysis of 39 cohorts.SettingEurope, North America, and Oceania.Population265 270 births.MethodsInformation on maternal pre‐pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used.Main outcome measuresGestational hypertension, pre‐eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth.ResultsHigher maternal pre‐pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31– 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain.ConclusionsMaternal pre‐pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre‐pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity.Tweetable abstractPromoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.

Streszczenie • Odwrotna zaleznośc pomiedzy spozyciem nieprzetworzonego mleka krowiego a zakazeniami ukladu oddechowego u niemowląt wskazuje na obecnośc przeciwzakaźnych i immunomodulujących cząsteczek związanych z tego typu zakazeniami u ludzi. • Zapobieganie zakazeniom ukladu oddechowego we wczesnym okresie zycia moze nie tylko ogolnie poprawiac stan tego ukladu, ale moze takze korzystnie wplywac na poźniejszy rozwoj ciezkich chorob ukladu oddechowego, jak np. astmy. Bezpieczne mikrobiologicznie, choc minimalnie przetworzone mleko moze miec istotny wplyw na zdrowie spoleczne w odniesieniu do czestych zakazen ukladu oddechowego. Wprowadzenie Karmienie piersią zapobiega zakazeniom ukladu oddechowego w pierwszych miesiącach zycia. Biorąc pod uwage wspolne ewolucyjne procesy adaptacyjne ludzi i bydla, mozliwe, ze mleko krowie wywiera podobny efekt ochronny u niemowląt u ludzi. Cel pracy Analiza wplywu spozywania surowego i przetworzonego mleka krowiego na najczestsze zakazenia ukladu oddechowego u niemowląt. Metody W ramach kohorty urodzeniowej w badaniu PASTURE obserwowano 983 niemowleta z terenow wiejskich z Austrii, Finlandii, Francji, Niemiec i Szwajcarii przez pierwszy rok zycia, obejmując lącznie 37 306 osobo-tygodni. Na podstawie cotygodniowych wpisow w dzienniczku stanu zdrowia analizowano spozycie roznych rodzajow mleka krowiego oraz wystepowanie niezytu blony śluzowej nosa, zakazenia ukladu oddechowego, zapalenia ucha i gorączki. Po 12 miesiącach pobierano probki krwi i oznaczano stezenie bialka C-reaktywnego. Wyniki W porownaniu z mlekiem UHT ( ultra-heat treatment ) spozywanie surowego mleka wykazywalo odwrotną zaleznośc z wystepowaniem niezytu blony śluzowej nosa (skorygowany iloraz szans z modeli longitudinalnych [95% CI]: 0,71 [0,54–0,94]), zakazen ukladu oddechowego (0,77 [0,59–0,99]), zapalenia ucha (0,14 [0,05–0,42]) i gorączki (0,69 [0,47–1,01]). Gotowane mleko wiejskie wykazalo podobną, choc nieco slabszą zaleznośc. Fabrycznie przetworzone mleko pasteryzowane wykazalo odwrotną zaleznośc z wystepowaniem gorączki. Spozywanie surowego mleka wiejskiego wiązalo sie odwrotnie zaleznie ze stezeniami bialka C-reaktywnego po 12 miesiącach (stosunek średnich geometrycznych [95% CI]: 0,66 [0,45–0,98]). Wnioski Spozywanie surowego mleka krowiego we wczesnym okresie zycia zmniejsza ryzyko wystepowania zakazen ukladu oddechowego i gorączki o okolo 30%. Biorąc pod uwage bardzo czeste wystepowanie zakazen ukladu oddechowego w pierwszym roku zycia oraz związane z tym koszty pośrednie i bezpośrednie wydaje sie, ze eliminacja zagrozen zdrowotnych związanych ze spozywaniem surowego mleka moglaby umozliwic ogromny wplyw minimalnie przetworzonego, ale pozbawionego patogenow mleka na zdrowie publiczne.

Background Farm exposure has been shown to protect from childhood asthma and allergic diseases, but underlying immunological mechanisms are not clear yet. Objective To explore whether farming lifestyle determines cytokine profile of peripheral blood mononuclear cells (PBMCs) of 4.5-year-old children (n = 88) from the Finnish PASTURE birth cohort study. Methods We analysed regulatory (IL-10, IL-2), T helper 1 (Th1)-associated (IL-12, IFN-gamma), inflammatory (IL-1 beta, TNF, CXCL8) and Th2-associated (IL-13) cytokines in unstimulated PBMCs and after a short-term (5 h) stimulation with lipopolysaccharide (LPS). Specific farm exposures (stables, hay barn, farm milk) at age 4 years were assessed from questionnaires. Results The unstimulated PBMCs of farm children produced more IL-10 (GMR 1.22, P = 0.032), IL-12 (GMR 1.24, P = 0.012) and IFN-gamma (GMR 1.24, P = 0.024) than those of non-farm children. Also, specific farm exposures were associated with higher spontaneous production of cytokines. The number of specific farm exposures tended to be dose dependently associated with higher spontaneous production of IFN-gamma (test for trends, P = 0.013) and lower LPS-induced production of TNF (test for trends, P = 0.025). Conclusion and Clinical Relevance Farming lifestyle seemed to be associated with increased spontaneous production of Th1 and regulatory cytokines. Decreased TNF responses to short-term LPS stimulation in farm-exposed children may imply tolerogenic immune mechanisms. These novel findings might contribute to the asthma and allergy protection in farm environment.

Introduction and Aims: Growing up in farm environment protects from asthma. The protective effect has been associated with special microbial exposures. Our aim in here was to test whether farm home microbiota could provide a model for asthma-protective indoor microbiome that would be protective also in a non-farm environment. Methods: We first modelled differences in house dust microbiota composition between farm and non-farm homes of 204 Finnish children. Association between asthma risk by age 6 years and modelled similarity of indoor microbiota to that in farm homes in early life was then analyzed in a second Finnish birth cohort of 182 children not living on farms. Results were replicated in a cross-sectional study of 1031 German children. Results: The asthma risk in children who grew up in non-farm homes decreased as the similarity of their early home microbiota to farm home microbiota increased (adjusted odds ratio [aOR] 0.40 per interquartile range [IQR] increase in modelled similarity; 95% confidence interval [CI] 0.19 to 0.82). The protective microbiota was low in Streptococcaceae relative to outdoor-associated taxa, increased e.g. by siblings and walking indoors with outdoor shoes. Also the asthma risk of German children decreased with the increasing similarity of their home microbiota to the microbiota in Finnish farm homes (aOR 0.65 per IQR increase in modelled similarity; 95% CI 0.46-0.91). Conclusions: These results identify the indoor dust microbiota composition as a definable, reproducible predictor of asthma risk and a novel modifiable target for asthma prevention.

Background: Childhood asthma prevalence is significantly greater in urban areas compared with rural/farm environments. Murine studies have shown that TNF-alpha-induced protein 3 (TNFAIP3; A20), an anti-inflammatory regulator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) signaling, mediates environmentally induced asthma protection. Objective: We aimed to determine the role of TNFAIP3 for asthma development in childhood and the immunomodulatory effects of environmental factors. Methods: In a representative selection of 250 of 2168 children from 2 prospective birth cohorts and 2 cross-sectional studies, we analyzed blood cells of healthy and asthmatic children from urban and rural/farm environments from Europe and China. PBMCs were stimulated ex vivo with dust from "asthma-protective'' farms or LPS. NF-kappa B signaling-related gene and protein expression was assessed in PBMCs and multiplex gene expression assays (NanoString Technologies) in isolated dendritic cells of schoolchildren and in cord blood mononuclear cells from newborns. Results: Anti-inflammatory TNFAIP3 gene and protein expression was consistently decreased, whereas proinflammatory Toll-like receptor 4 expression was increased in urban asthmatic patients (P

Background Dietary changes are suggested to play a role in the increasing prevalence of allergic diseases and asthma. Short-chain fatty acids (SCFAs) are metabolites present in certain foods and are produced by microbes in the gut following fermentation of fibers. SCFAs have been shown to have anti-inflammatory properties in animal models. Our objective was to investigate the potential role of SCFAs in the prevention of allergy and asthma. Methods We analyzed SCFA levels by high-performance liquid chromatography (HPLC) in fecal samples from 301 one-year-old children from a birth cohort and examined their association with early life exposures, especially diet, and allergy and asthma later in life. Data on exposures and allergic diseases were collected by questionnaires. In addition, we treated mice with SCFAs to examine their effect on allergic airway inflammation. Results Significant associations between the levels of SCFAs and the infant's diet were identified. Children with the highest levels of butyrate and propionate (≥95th percentile) in feces at the age of one year had significantly less atopic sensitization and were less likely to have asthma between 3 and 6 years. Children with the highest levels of butyrate were also less likely to have a reported diagnosis of food allergy or allergic rhinitis. Oral administration of SCFAs to mice significantly reduced the severity of allergic airway inflammation. Conclusion Our results suggest that strategies to increase SCFA levels could be a new dietary preventive option for allergic diseases in children.

Asthma prevalence has increased in epidemic proportions with urbanization, but growing up on traditional farms offers protection even today

Background: The gut microbiota has been associated with overweight and obesity in adults, but the evidence in children is limited. Our aim was to study whether composition of the gut microbiota at the age of 3 years is associated with overweight/obesity in children cross-sectionally. Methods: Children, who participated in a clinical trial of prenatal vitamin-D supplementation (VDAART), underwent standardized height and weight measurements, and collection of stool samples at three years of age. 16S rRNA sequencing (V4 region) of the stool samples were performed with Illumina MiSeq. Associations between microbiota and overweight/obesity (body mass index z-scores > 85th percentile) was analyzed using logistic regression. Results: Out of 502 children, 146 (29%) were categorized as overweight/obese. Maternal pre-pregnancy BMI, birth weight and length, formula feeding during the first year, high frequency of fast food consumption, and time watching TV or computer screen at 3 years were the risk factors for overweight/obesity. Of the top 20 most abundant genera, high relative abundance of Parabacteroidetes(Bacteroidetes;Bacteroidales) (aOR(95%CI): 0.69(0.53, 0.90, p=0.007) per interquartile increase) and unassigned genus within Peptostreptococcae family were inversely associated with overweight/obesity, whereas high relative abundance of Dorea(Firmicutes;Clostridiales) (1.23 (1.05,1.43, p=0.009)) was positively associated. Associations were independent of each other. No associations were found between diversity indices and overweight/obesity. Conclusions: Our data suggest that some of the differences in gut composition of bacteria between obese and non-obese adults can already be observed in 3-year old children. Longitudinal studies will be needed to determine long-term effects.

Background/aim The immune system and gut microbiota may play a role in the cognitive development. The home microbiota are a source of microbial exposure affecting immunological and maybe gut microbiota development. Thus, it may contribute to cognitive development. Here, we assess the association between early life home dust microbial diversity and hyperactivity/inattention symptoms at 10 and 15 years old. Methods A random sample enriched with subjects with hyperactivity/inattention at age 15 years were selected from the German LISA birth cohort. Bedroom floor dust samples were collected at age 3 months and bacterial diversity was defined by richness (number of OTUs and Chao1) and diversity indices (Shannon and Simpson) calculated from Illumina MiSeq sequencing data of 16S rRNA gene DNA amplicons. Hyperactivity/inattention was defined based on the scores of the Strengths and Difficulties questionnaire (SDQ) at ages 10 (filled by parents) and at 15 years (self-administered), using a cut-off ≥7. With adjusted logistic regression models we investigate the associations between symptoms and 4 diversity indices in tertiles. At age 10, models were weighted by the inverse of the sampling weights. Results We included 226 individuals with information on indoor microbial diversity and hyperactivity/inattention symptoms. The median values of the diversity indices were higher among children without symptoms at age 10 for bacteria and at age 15 for fungi. After adjustment, hyperactivity/inattention at age 10 was inversely associated with bacterial richness (number of observed OTUs medium vs low diversity: OR=0.4; CI: 0.2 to 0.8; Chao1 medium vs low diversity: OR=0.3; CI: 0.1 to 0.5; high vs low: OR=0.3; CI: 0.2 to 0.6), and positively associated with fungal Chao1 (high vs low: OR=2.1; CI: 1.1 to 4.0), Shannon (medium vs low: OR=2.8; CI: 1.3 to 5.8), and Simpson (high vs low: OR=4.7; CI: 2.4 to 9.3). No significant associations were observed between the indices and hyperactivity/inattention at age 15. Conclusion Our results suggest that early life exposure to microbial diversity may play a role in the development of hyperactivity/inattention during childhood. Exposure to rich bacterial environment may protect from developing hyperactivity/inattention, while high fungal diversity may have the opposite effect. Further larger studies are needed to confirm our results.

We analysed floor dust samples from 65 children's bedrooms in Finland collected in 2014/2015 for 62 different per- and polyfluoroalkyl substances (PFASs) with a simple and highly efficient method. Validation results from the analysis of standard reference material (SRM) 2585 were in good agreement with literature data, while 24 PFASs were quantified for the first time. In the dust samples from children's bedrooms, five perfluoroalkyl carboxylic acids (PFCAs) and perfluorooctane sulfonic acid (PFOS) were detected in more than half of the samples with the highest median concentration of 5.26 ng/g for perfluorooctanoic acid (PFOA). However, the dust samples were dominated by polyfluoroalkyl phosphoric acid esters (PAPs) and fluorotelomer alcohols (FTOHs) (highest medians: 53.9 ng/g for 6:2 diPAP and 45.7 ng/g for 8:2 FTOH). Several significant and strong correlations (up to ρ = 0.95) were found among different PFASs in dust as well as between PFASs in dust and air samples (previously published) from the same rooms. The logarithm of dust to air concentrations (log K

BackgroundGestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies.MethodsWe used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America, and Oceania. Of these women, 9065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3597 (1.6%), and 1095 (0.5%) were underweight, normal weight, overweight, and grades 1, 2, and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2, and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale, and shape.ResultsWe observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40weeks was 14.2kg (11.4-17.4) for underweight women, 14.5kg (11.5-17.7) for normal weight women, 13.9kg (10.1-17.9) for overweight women, and 11.2kg (7.0-15.7), 8.7kg (4.3-13.4) and 6.3kg (1.9-11.1) for grades 1, 2, and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications.ConclusionsGestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice., ABCDr This work was supported by the Netherlands Organization for Health Research and Development (ZonMw) (TOP grant, 40-00812-98-11010).r ALSPACr The UK Medical Research Council and Wellcome (Grant ref.: 102215/2/13/2) and the University of Bristol provide core support fog ALSPAC. This study has received support from the US National Institute of Health (R01 DK10324) and European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no 669545. DA Lawlor works in a unit that receives UK MRC funding (MQ_UU_12013/5) and is an NIHR senior investigator (NF-Sl-0611-10196).r AOB/Fr All Our Families is funded through Alberta Innovates Interdisciplinary Team Grant 4200700595, the Alberta Children's Hospital Foundation, and the Max Bell Foundation.r DNBCr The Danish National Research Foundation has established the Danish Epidemiology Science Centre that initiated and created the Danish National Birth Cohort. The cohort is furthermore a result of a major grant from this foundation. Additional support for the Danish National Birth Cohort is obtained from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Augustinus Foundation, and the Health Foundation. The DNBC 7-year follow-up is supported by the Lundbeck Foundation (195/04) and the Danish Medical Research Council (SWF 0646).r EDENr The EDEN Study was supported by Foundation for medical research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte sante 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A) and Human Nutrition National Research Programs, Paris-Sud LJniversity, Nestle, French National Institute for Population Health Surveil lance (InVS), French National Institute for h-lealth Education (APES), the European Union FP7 programmes (FP7/2007-2013, HELIX, ESCAPE, ENRIECO, Medall projects), Diabetes National Re.search Program (through a collaboration with the French Association of Diabetic Patients (AFD)), French Agency for Environmental Health Safety (now ANSES), Mutuelle Generale de l'Education Nationale a complementary health inswance (MGEN), French national agency for food security, French-speaking association for the study of diabetes and metabolism (ALFEDIAM).r FCOUr FCOU study is supported by the US National Institutes of Health Fogarty International Center, US NIEHS, US CDC, US PA, and National Academy of Medical Sciences of Ukraine.r GASPIIr Ministry of Health.r GECKO Drenther The GECKO Drenthe birth cohort was funded by an unrestricted grant of Hutchison Whampoa Ld, Hong Kong and supported by the University of Groningen, Well Baby Clinic Foundation Icare, Noodlease, Paediatric Association Of The Netherlands and Youth Health Care Drenthe.r Generation Rr The general design of the Generation R Study is made possible by financial support from the Erasmus MC, University Medical Center, Rotterdam, Erasmus University Rotterdam, Netherlands Organization for Health Research and Development (ZonMw), Netherlands Organisation for Scientific Research (NWO), Ministry of Health, Welfare and Sport and Ministry of Youth and Families. Research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013), project ErlyNutrition under grant agreement no. 289346, the European Union's Horizon 2020 research and innovation programme under grant agreement no.; 633595 (DynalHEALTH)and the European Union's Horzon 2020 research and Innovation programme under grant agreement 733206 (LifeCycle Project). Romy Gaillard received funding from the Dutch Heart Foundation (grant number 2017T013) and the Dutch Diabetes Foundation (grant number 2017.81.002). Vincent Jaddoe received grants from the Netherlands Organization for Health Research and Development (VIDI 016.136.361) and the European Research Council (Consolidator Grant, ERC-2014-CoG-648916).r Generation XXIr Generation XX: was funded by Pmgrama Operational de Saude-Saude XXI, Quadro Comunitario de Apoio III and Administracao Regional de Saude Norte (Regional Department of Ministry of Health). This study was funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology FCT (Portuguese Minstry of Science, Technology and Higher Education) (POCI-01-0145-FEDER-016837), under the project PathMOB.: Risco cardiomwtabolico na infancia: desde o inicio da vida ao fim da infancia (Ref. FCT PIDc/DTP-EP1/3306/2014) and the Unidade de Investigacao em Epiclemiologia-Instituto de Saude Publica da Universidade do Porte (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UlD/DTP/04750/2013). AC Santos holds a FG Investigator contract IF/01060/2015.r GENESISr The study was supported by a research grant from Friesland Foods Hellas. Gen3G Gen3G was supported by a Fonds de recherche du Quebec en sante (FRQ-S) operating grant (grant 4206971; a Canadian Institute of Health Reseach (CIHR) Operating grant (grant WOE) 115071); a Diabete Quebec grant and a Canadian Diabetes Association operating grant (grant #OG-3-08-2622-JA).r GINIplusr The GINIplus study was mainly supported for the first 3 years of the Federal Ministry for Education, Science, Research and Technology I:interventional arm) and Helmholtz Zentrum Munich (former GSF) (observational arm). The 4-year, 6-year, 10-year, and 15-year follow-up examinations of the GINIplus Study were covered from the respective budgets of the 5 study centers Helmoltz Zentrum Munich (former GSF), Research Institute at Marien-Hospital Wesel, LMU Munich, TU Munich and from 6 years onwards also from IUF-Leibniz Research-Institute for Environmental Medicine at the University of Dusseldorp and a grant from the Federal Ministry for Environment (IUF Dus seldoit FKZ 20462296). Further, the 15 year follow-up examination of the GINIplus study was supported by the Commission of the European Communities, the 7th Framework Program: MeDALL project, and as well by the companies Mead Johnson and Nestle.r HUMISr European Community's Seventh Framework Programme (P7/2007-2013) under grant agreements Early Nutrition no. 289346 and by funds from the Norwegian Research Council's MILPAAHEL programme, project no. 213148. INMA-Sabadellr This study was funded by grants from the Institute de Salad Carlos III (Red INMA G03/176) and the Genera tat de Catalunya-CIRIT (1999SGR 00241).r INMA-Valenciar This study was funded by Grants from UE (P7-ENV-2011 cod 282957 and HEALTH2010.2.4.5-1), Spain: ISCIII (G03/176; FIS-FEDER: P109/02647, PI11/01007, PI11/02591, PI11/02038, PI1.3/1944-, PI13/2032, P114/00891, PI14/01687, and PI16/1288; Miguel Servet-FEDER CP11/00178, CP15/00025, and CPII16/00051), and Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249).r INMA-Gipuzkoar This study was funded by grants from the Institute. de Salad Carlos III (Red INMA G03/176).; r KOALAr Data collection for the KOALA study from pregnancy up to age 1 year was financially supported by grants from Royal Friesland Foods (Leeuwarden); Trio dos Foundation (Zeist); Phoenix Foundation; Raphael Foundation; Iona Foundation, Foundation for the Advancement of Heilpedagogie (all in the Netherlands).r Krakow Cohortr The study received funding from a NIEHS R01 grants entitled: Vulnerability of the Fetus/Infant to PAH, PM2.5 and FTS and Developmental effects of early-life exposure to airborne PAC (R01ES010165 and R01ES015282) and from The Lundin Foundation, The John and Wendy Neu Family Foundation, The Gladys and Roland Harriman Foundation and an Anonymous Foundation.r LISAplusr The LISAplus study was mainly supported by grants from the Federal Ministry for Education Science, Research and Technology and in addition from Helmholtz Zentrum Munich (former GSF), Helmholtz Centre for Environmental Research-UFZ, Leipzig, Research Institute at Marien-Hospital Wesel, Pediatric Practice, Bad Honnef for the first 2 years. The 4-year, 6-year, 10-year, and 15-year follow-up examinations of the LISA-plus Study were covered from the respective budgets of the involved partners (Helmholtz Zentrum Munich (former GSF), Helmholtz Centre for Enironmental Research-UFZ, Leipzig, Research Institute at Marien-Hospital Wesel Pediatric Practice, Bad Honnef, IUr-Leibniz-Research Institute for Environmental Medicine at the University of Dusseldorf) and in addition by a grant from the Federal Ministry for Environment (IUF-Dussedorf, FKZ 204622961. Further, the 15-year follow-up examination of the LISAplus study was supported by the Commission of the FaMpean Communities and the 7th Framework Program: McDALL project.r LUKAS The grants from the Academy of Finland (grants 139021;287675); the Juho Vainio Foundation; the Foundation for Pediatric Research; EVE/VTR-funding; Paivikki and Saran Sohlberg Foundation; The Finnish Cultural Foundation; European Union QLK4-CT-2001-00250; and by the National Institute for Health and Welfare, Finland.r MoBar The Norwegian Mother and Child Cohort Study is supported by the Norwegian [Ministry of Health and Care. Services and the Ministry of Education and Research, NIH/NIEHS (contract no. N01-ES-75558), NIH/NINDS (grant. no. 1 UO1 NS 047537-01 and grant no. 2 UO1 NS 047537-06A1).r NINFEAr The NINFEA cohort was partially funded by the Compagnia San Paolo Fundation and by the Piedmont Region.r PELAGIEr The Pelagic cohort was supported by the French National Research Agency (ANR-2010-PRSP-007) and the French Research Institute for Public Health (AMC11004NSA-DGS).r PIAMAr The PIAMA study was supported by the Netherlands Organization for Health Research and Development; The Netherlands Organization for Scientific Research; The Netherlands Asthma Fund; The Netherlands Ministry of Spatial Planning, Housing, and the Environment; and The Netherlands Ministry of Health, Welfare, and Sport.r Piccolipiur The Piccolipiu project was financially supported by the Italian National Center for Disease Prevention and Control (CCM grants years 2010 and 2014) and by the Italian Ministry of Health (art 12 and 12 bis D.Igs 502/92).r PRIDE Studyr The PRIDE Study is supported by grants from the Netherlands Organization for Health Research and Development, the Radboud Institute for Health Sciences, and the Lung Foundation Netherlands.r Project Vivar National Institutes of Health (R01 HD034568, UGOD023286).; r RAINE Studyr The Western Australian Pregnancy Cohort (Raine Study) has been funded by program and project grants from the Australian National Health and Medical Research Council, the Commonwealth Scientific and Industrial Research Organization, Healthway, and the Lions Eye Institute in Western Australia. The University of Western Australia (UWA), Curtin University, the Raine Medical Research Foundation, the Telethon Kids Institute, the Women's and Infant's Research Foundation (KEMH), Murdoch University, The University of Notre Dame Australia, and Edith Cowan University provide funding for the Core Management of the Raine Study.r REPRO_PLr National Science Centre, Poland, under the grant DEC-2014/15/3/NZ7/00998, FP7 HEALS Grant No. 603946 and the Ministry of Science and Higher Education, under grant agreement no. 3068/7.PR./2014/2.r RHEAr The Rhea project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP&.STREP Hiwate, EU FP7 ENV.2007.1222 Project No. 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009-single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No. 226285 ENIIIECO, EU-FP/-HEALTH-2012 Proposal No 308333 HELIX) and the Greer: Ministry of Health (Program of Prevention of obesity and ileuMdevelopmental disorders in preschool children, in Heraklion District, Crete, Greece: 2011-2014; Rhea Plus: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health 2012-15).r Slovak PCB studyr Support was provided by US National Institutes of Health grants R01 CA096525, R03 TW007152, P30 E5001247, and K12 ES019852.r STEPSr This study was supported by the University of Turku, Abo Akademi University, the Turku University Hospital, and the City of Turku, as well as by the Academy of Finland (grants 121569 and 123571), the Juno Vainio Foundation, the Yrjo Jahnsson Foundation, the TorKu.r SWSr The SWS is supported by grants from the Medical Research Council, National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service Foundation Trust, and the European Union's Seventh Framework Programme. (P7/2007-2013), project EarlyNutrifion (grant 289346). Study participants were drawn from a cohort study funded by the Medical Research council and the Dunhill Medical Trust.

Background Early life farm exposures have been shown to decrease the risk of allergic diseases. Dendritic cells (DCs) may mediate asthma-protective effect of farm exposures as they play an important role in the development of immunity and tolerance. Our aim was to investigate whether the numbers and phenotypes of circulating DCs at age 6 are associated with farming, asthma, and atopy in a selected sample of French and Finnish children from the PASTURE study. Methods We studied 82 farm and 86 nonfarm children with and without asthma. Using flow cytometry, BDCA1+ CD11c+ myeloid DC1s (mDC1), BDCA3+high mDC2s and BDCA2+ plasmacytoid DCs (pDCs) were identified and expressions of CD86, immunoglobulin-like transcript 3 (ILT3) and ILT4 were analyzed. Questionnaires were used to assess prenatal and lifetime patterns of farm exposures and to define asthma. Atopic sensitization was defined by specific IgE measurements. Results The percentage of mDC2 cells was lower in farm children (0.033 ± 0.001) than in nonfarm children (0.042 ± 0.001; P = 0.008). Similar associations were found between mDC2 percentage and prenatal (P = 0.02) and lifetime exposure to farm milk (P = 0.03) and stables (P = 0.003), but these associations were not independent from farming. Asthma was positively associated with ILT4 + mDCs (P = 0.04) and negatively with CD86 + pDCs (P = 0.048) but only in nonfarm children. Conclusions Inverse association between farm exposure and mDC2 percentage suggest that this DC subset may play a role in farm-related immunoregulation.

This study investigated the association between confirmed moisture damage in homes and systemic subclinical inflammation in children. Home inspections were performed in homes of 291 children at the age of 6 years. Subclinical inflammation at the age of 6 years was assessed by measuring the circulating levels of C-reactive protein (CRP) and leukocytes in peripheral blood and fractional exhaled nitric oxide (FeNO). Proinflammatory cytokines interleukin (IL)-1β and IL-6 and tumor necrosis factor (TNF)-α were measured in unstimulated, and in phorbol 12-myristate 13-acetate and ionomycin (PI), lipopolysaccharide (LPS), or peptidoglycan (PPG)-stimulated whole blood. Major moisture damage in the child's main living areas (living room, kitchen, or child's bedroom) and moisture damage with mold in the bathroom were associated with increased levels of CRP and stimulated production of several proinflammatory cytokines. There were no significant associations between moisture damage/visible mold and leukocyte or FeNO values. The results suggest that moisture damage or mold in home may be associated with increased systemic subclinical inflammation and proinflammatory cytokine responsiveness.

BACKGROUND: Excess moisture and visible mold are associated with increased risk of asthma. Only a few studies have performed detailed home visits to characterize the extent and location of moisture damage and mold growth. METHODS: Structured home inspections were performed in a birth cohort study when the children were 5 months old (on average). Children (N = 398) were followed up to the age of 6 years. Specific immunoglobulin E concentrations were determined at 6 years. RESULTS: Moisture damage and mold at an early age in the child’s main living areas (but not in bathrooms or other interior spaces) were associated with the risk of developing physician-diagnosed asthma ever, persistent asthma, and respiratory symptoms during the first 6 years. Associations with asthma ever were strongest for moisture damage with visible mold in the child’s bedroom (adjusted odds ratio: 4.82 [95% confidence interval: 1.29–18.02]) and in the living room (adjusted odds ratio: 7.51 [95% confidence interval: 1.49–37.83]). Associations with asthma ever were stronger in the earlier part of the follow-up and among atopic children. No consistent associations were found between moisture damage with or without visible mold and atopic sensitization. CONCLUSIONS: Moisture damage and mold in early infancy in the child’s main living areas were associated with asthma development. Atopic children may be more susceptible to the effects of moisture damage and mold.

Introduction and aims: Indoor microbial diversity only partly explains the protective effects of farming on asthma development in children. The importance of taxonomic composition of the indoor microbiota was therefore studied. Methods: Living room dust was collected at age of 2 months from homes of 197 rural children, half from farms (LUKAS1), and of 182 mostly sub-urban children (LUKAS2). Bacterial 16S rRNA gene (V4) and fungal ITS1 region amplicons were sequenced in Illumina MiSeq V3 platform. Raw data was processed using QIIME. Axis scores from PCoA analyses of abundance weighted bacterial Unifrac data were used in logistic regression to predict the probability of being a farmer in LUKAS1 (called here FARM index). FaRM index was then also applied to LUKAS2. Associations with asthma at age 6 years were analyzed using logistic regression adjusting for potential confounders. Results: The Indoor bacterial/archaeal microbiota of the farming homes was characterized both by high richness of more rare taxa, mostly absent in the non-farm homes, but also with high relative abundance of specific phyla such as the Actinobacteria and Chloroflexi. The FaRM- index explained the protective farming effect in LUKAS1 and was also strongly dose-dependently associated with protection from asthma in LUKAS2. Exposure to cattle and determinants indicating microbial carriage from outdoors were the strongest determinants of the protective microbial exposure. Only weak associations were seen with fungi. Conclusions: These data suggest that in addition to diversity, farm-like taxonomic composition of the indoor bacterial/archaeal microbiota is important in asthma prevention

Background Early-life respiratory tract infections could affect airway obstruction and increase the risk of asthma in later life. Objective We examined the associations of early-life respiratory tract infections with lung function and asthma in children. Methods We used individual participant data of 154,492 children from 37 birth cohorts to examine the associations of upper (URTI) and lower respiratory tract infections (LRTI) by the age of 6 months, 1, 2, 3, 4 and 5 years with forced expiratory volume in 1 second (FEV 1 ), forced vital capacity (FVC) FEV 1 /FVC, forced expiratory flow at 75% of FVC (FEF 75 ) and asthma at a mean age of 7 (SD 2) years. We used multilevel mixed effect models, to take clustering of participants within cohorts into account, and adjusted for socio-economic, lifestyle and growth factors. Results URTI were not associated with lung function. URTI at all ages were associated with an increased risk of asthma (OR (95% CI): ranging from 1.25 (1.15, 1.34) to 1.56 (1.47, 1.66)). LRTI at all ages were associated with a lower FEV 1 , FEV 1 /FVC and FEF 75 (Z-score (95% CI): ranging from -0.07 (-0.14, -0.00) to -0.24 (-0.38, -0.10)), except for LRTI at age 6 months with FEF 75 , and an increased risk of asthma (OR (95% CI): ranging from 2.00 (1.85, 2.10) to 3.72 (3.19, 3.85)). Conclusion Early-life lower respiratory tract infections are associated with lower lung function and increased risk of asthma in later life, while upper respiratory tract infections are associated with asthma only. These findings support the hypothesis that early-life respiratory tract infections might affect long term respiratory morbidity.

Background The limited understanding of microbial characteristics in moisture-damaged buildings impedes efforts to clarify which adverse health effects in the occupants are associated with the damage and to develop effective building intervention strategies. The objectives of this current study were (i) to characterize fungal and bacterial microbiota in house dust of severely moisture-damaged residences, (ii) to identify microbial taxa associated with moisture damage renovations, and (iii) to test whether the associations between the identified taxa and moisture damage are replicable in another cohort of homes. We applied bacterial 16S rRNA gene and fungal ITS amplicon sequencing complemented with quantitative PCR and chemical-analytical approaches to samples of house dust, and also performed traditional cultivation of bacteria and fungi from building material samples. Results Active microbial growth on building materials had significant though small influence on the house dust bacterial and fungal communities. Moisture damage interventions—including actual renovation of damaged homes and cases where families moved to another home—had only a subtle effect on bacterial community structure, seen as shifts in abundance weighted bacterial profiles after intervention. While bacterial and fungal species richness were reduced in homes that were renovated, they were not reduced for families that moved houses. Using different discriminant analysis tools, we were able identify taxa that were significantly reduced in relative abundance during renovation of moisture damage. For bacteria, the majority of candidates belonged to different families within the Actinomycetales order. Results for fungi were overall less consistent. A replication study in approximately 400 homes highlighted some of the identified taxa, confirming associations with observations of moisture damage and mold. Conclusions The present study is one of the first studies to analyze changes in microbiota due to moisture damage interventions using high-throughput sequencing. Our results suggest that effects of moisture damage and moisture damage interventions may appear as changes in the abundance of individual, less common, and especially bacterial taxa, rather than in overall community structure. Electronic supplementary material The online version of this article (10.1186/s40168-017-0356-5) contains supplementary material, which is available to authorized users.

The contamination levels and patterns of perfluoroallcyl acids (PFAAs) and their precursors in indoor air of children's bedrooms in Finland, Northern Europe, were investigated. Our study is among the most comprehensive indoor air monitoring studies (n = 57) and to our knowledge the first one to analyse air in children's bedrooms for PFASs (17 PFAAs and 9 precursors, including two acrylates, 6:2 FTAC and 6:2 FTMAC). The most frequently detected compound was 8:2 fluorotelomer alcohol (8:2 FTOH) with the highest median concentration (3570 pg/m(3)). FTOH concentrations were generally similar to previous studies, indicating that in 2014/2015 the impact of the industrial transition had been minor on FTOH levels in indoor air. However, in contrast to earlier studies (with one exception), median concentrations of 6:2 FTOH were higher than 10:2 FTOH. The C8 PFAAs are still the most abundant acids, even though they have now been phased out by major manufacturers. The mean concentrations of FOSE/As, especially MeFOSE (89.9 pg/m(3)), were at least an order of magnitude lower compared to previous studies. Collectively the comparison of FTOHs, PFAAs and FOSE/FOSAs with previous studies indicates that indoor air levels of PFASs display a time lag to changes in production of several years. This is the first indoor air study investigating 6:2 FTMAC, which was frequently detected (58%) and displayed some of the highest maximum concentrations (13 000 pg/m(3)). There were several statistically significant correlations between particular house and room characteristics and PFAS concentrations, most interestingly higher EtFOSE air concentrations in rooms with plastic floors compared to wood or laminate. (C) 2016 Published by Elsevier Ltd.