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OBJECTIVE: To compare parent reported physician diagnosed asthma from questionnaires for epidemiological purposes, to general practitioner (GP) recorded childhood asthma.METHODS: This study was embedded in the KOALA Birth Cohort Study with regular follow-up by ISAAC core questions on asthma in 2834 children in two different recruitment groups, with 'conventional' lifestyles or 'alternative' lifestyles. At age 11-13 years these data were linked to data extracted from GP records. We compared parent reported physician diagnosed asthma, asthma medication use, and current asthma with GP recorded asthma diagnosis and medication. Two different combinations of questions were used to define current asthma (i.e. ISAAC and MeDALL based definition).RESULTS: Among 958 children with information provided both by the parents and GPs, 98 children (10.2%) had parent reported physician diagnosed asthma, 115 children (12.0%) had a GP recorded asthma diagnosis (Cohen's kappa 0.49; 95% CI 0.40 to 0.57). Discrepant cases showed that asthma symptoms at an early age led to different labeling between parents and GP. The agreement between ISAAC based definition and MeDALL based definition was excellent (Cohen's kappa 0.82; 95% CI 0.74 to 0.88).CONCLUSION: Parent reported physician diagnosed asthma and GP recorded childhood asthma had only moderate agreement, and is possibly influenced by labeling early transient wheeze as asthma diagnosis. It is important that parent reported physician diagnosed asthma is combined with additional questions such as current asthma symptoms and asthma medication use, as used in ISAAC or MeDALL based current asthma, in order to obtain reliable information for epidemiological research.

Objective: To evaluate longitudinal associations between recreational screen time and sleep in early childhood, and attention-deficit/hyperactivity disorder (ADHD) at age 8 to 10 years. Method: Questionnaires from 2,768 mother-child pairs from the Dutch KOALA Birth Cohort Study were used. General estimating equation logistic regression analyses examined associations between screen time and sleep at age 2, 4, and 6, and ADHD at age 8 to 10. Linear regression analysis examined associations between television time, sleep and CBCL/2-3 scores at age 2. Results: Longitudinally, neither screen time nor sleep were associated with ADHD. Cross-sectionally, CBCL/2-3 externalizing symptom scores increased by 0.03 with every hour television time (95% CI 0.002–0.05) and increased by 0.02 per hour of less sleep (95% CI −0.03–−0.01). Conclusion: Despite an association with externalizing symptoms at age 2, screen time and sleep in early childhood were not associated with ADHD. Carefulness is warranted when extrapolating cross-sectional associations at early age to an ADHD diagnosis.

A solid-phase extraction procedure was optimized to extract 3-fucosyllactose and other human milk oligosaccharides (HMOs) from human milk samples separately, followed by absolute quantitation using high-performance anion-exchange chromatography-pulsed amperometric detection and porous graphitized carbon-liquid chromatography-mass spectrometry, respectively. The approach developed was applied on a pilot sample set of 20 human milk samples and paired infant feces collected at around 1 month postpartum. One-dimensional 1H nuclear magnetic resonance spectroscopy was employed on the same samples to determine the relative levels of fucosylated epitopes and sialylated (Neu5Ac) structural elements. Based on different HMO consumption patterns in the gastrointestinal tract, the infants were assigned to three clusters as follows: complete consumption; specific consumption of non-fucosylated HMOs; and, considerable levels of HMOs still present with consumption showing no specific preference. The consumption of HMOs by infant microbiota also showed structure specificity, with HMO core structures and Neu5Ac(α2-3)-decorated HMOs being most prone to degradation. The degree and position of fucosylation impacted HMO metabolization differently.

Purpose It is controversial whether a higher intake of n-3 long-chain polyunsaturated fatty acids (n-3 LC PUFA) through breastfeeding is associated or not to a lower blood pressure (BP) during childhood. We aimed to clarify this point by undertaking a meta-analysis involving the data from seven European birth cohorts. Methods We searched https://www.birthcohort.net for studies that had collected breast milk samples, and had at least one BP measurement in childhood. Principal investigators were contacted, and all agreed to share data. One additional study was identified by contacts with the principal investigators. For each cohort, we analyzed the association of breast milk n-3 LC PUFAs with systolic and diastolic BP with linear mixed effects models or linear regression, and pooled the estimates with a random effects model. We also investigated age-specific and sex-specific associations. Results A total of 2188 participants from 7 cohorts were included. Overall, no associations between breast milk n-3 LC PUFAs and BP were observed. In the pooled analysis, each 0.1 wt% increment in breast milk docosahexaenoic acid (DHA) was associated with a 1.19 (95% CI − 3.31, 0.94) mmHg lower systolic BP. Associations were similar for boys and girls and at different ages. Conclusion In this individual participant meta-analysis, we found no evidence for an association between breast milk n-3 LC PUFAs and BP.

Scope Folic acid supplementation during pregnancy may lead to an imbalance when vitamin B12 intake is low (folate trap) and may affect child's growth. Methods The authors study the association between third trimester maternal intakes of folate and B12 and birthweight and postnatal growth of 2632 infants from the KOALA Birth Cohort Study. Plasma vitamin biomarkers are measured in 1219 women. Results Imbalanced total intakes (folate > 430 mu g day(-1) combined with B12 < 5.5 mu g day(-1)) are not associated with birthweight [beta adj (95% CI) = -14.87 (-68.87, 39.13)] compared with high intakes of both. Imbalanced intake is associated with a lower z score of weight at 1-2 years [beta adj = -0.14 (-0.25, -0.03)]. Having red blood cell folate > 745 nmol L-1 and plasma B12 < 172 pmol L-1 is not associated with birthweight [beta adj = -7.10 (-97.90, 83.71) g]. Maternal dietary B12 intake [beta adj = -9.5 (-15.6, -3.3)] and plasma methylmalonic acid [beta adj = 234 (43, 426)] are associated with birthweight. Conclusion Low maternal dietary B12 intake and elevated methylmalonic acid rather than imbalanced vitamins are associated with higher birthweight, suggesting that low maternal B12 can predispose the infants for later obesity.

Alternative lifestyles are likely to be associated with distinct usage of specific medicinal products. Our goal was to find out whether the intake of antibiotics during pregnancy and by children differs according to whether the mothers have alternative or conventional lifestyles. Therefore, we investigated the use of antibiotics by pregnant women and by children up to 11 years of age participating in the KOALA Birth Cohort Study. This cohort comprises two recruitment groups of mother–infant pairs, one with alternative lifestyles (selected via organic food shops, anthroposophic clinicians and midwives, anthroposophic under-five clinics, Rudolf Steiner schools and relevant magazines, n = 491) the other with conventional lifestyles (no selection based on lifestyle, n = 2343). Mothers in the alternative lifestyle group more frequently adhered to specific living rules and identified themselves with anthroposophy more than mothers in the conventional lifestyle group. The results revealed significant differences in antibiotic use during pregnancy and in children from 3 months to 10 years of age between the two groups. The rate of antibiotic use in children was consistently lower in the alternative lifestyle group than in the conventional lifestyle group. Antibiotic use in pregnancy was higher in low educated women, and maternal antibiotic use during lactation was higher after an instrumented delivery in hospital. Antibiotic use in the infant was higher when they had older sibs or were born in hospital, and lower in those who had been longer breastfed. After adjustment for these factors, the differences in antibiotic use between the alternative and conventional groups remained. The results suggest that an alternative lifestyle is associated with cautious antibiotic use during pregnancy, lactation and in children.

Contains fulltext : 219883.pdf (Publisher’s version ) (Open Access) BACKGROUND: Sedentary behavior and decreased physical activity are possible risk factors for developing asthma. This longitudinal study investigates the association between physical activity and subsequent asthma. We hypothesize that children with decreased physical activity at early school age, have higher risk of developing asthma. METHODS: One thousand eight hundred thirty-eight children from the KOALA Birth Cohort Study were analyzed. Children who were born prematurely or with congenital defects/diseases with possible influence on either physical activity or respiratory symptoms were excluded. Physical activity, sedentary behavior, and screen time were measured at age 4 to 5 years by questionnaire and accelerometry in a subgroup (n = 301). Primary outcome was asthma, assessed by repeated ISAAC questionnaires between age 6 and 10. Secondary outcome was lung function measured by spirometry in a subgroup (n = 485, accelerometry subgroup n = 62) (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC] and FEV1/FVC ratio) at age 6 to 7 years. RESULTS: Reported physical activity was not associated with reported asthma nor lung function. Accelerometry data showed that daily being 1 hour less physically active was associated with a lower FEV1/FVC (z score beta, -0.65; 95% confidence interval, -1.06 to -0.24). CONCLUSIONS: Physical activity at early school age was not associated with reported asthma development later in life. However, lung function results showed that sedentary activity time was associated with lower FEV1/FVC later in childhood. As this is the first longitudinal study with objectively measured physical activity and lung function, and because the subgroup sample size was small, this result needs replication. 01 januari 2020

Background: The effect of vitamin B-12 from different animal foods on vitamin B-12 biomarker status has not previously been evaluated in pregnant women.Objective: We examined the association of vitamin B-12 intake from dairy, meat, fish (including shellfish), and eggs with circulating concentrations of vitamin B-12 biomarkers and with the presence of vitamin B-12 deficiency in 1266 pregnant women participating in the KOALA Birth Cohort Study.Methods: Blood samples were collected in weeks 34-36 of pregnancy, and vitamin B-12 intake from foods and supplements was estimated with a semiquantitative food-frequency questionnaire (FFQ). Total vitamin B-12, holotranscobalamin (holoTC), and methylmalonic acid (MMA) were determined in plasma. Vitamin B-12 deficiency was defined as holoTC 0.45 mu mol/L. Associations were evaluated with linear and logistic regression analyses, adjusting for potential confounders.Results: Significant dose-response relations were observed between vitamin B-12 intake from dairy, meat, and fish and plasma vitamin B-12, holoTC, and MMA [P-trend for (shell) fish with MMA = 0.002; P-trend for dairy, meat, and fish with all other markers Conclusions: In pregnant Dutch women, higher intakes of vitamin B-12 from dairy, meat, and fish were positively associated with vitamin B-12 status, suggesting that dairy, meat, and fish are good sources of bioactive vitamin B-12 in pregnancy. Nevertheless, for (lacto-) vegetarians, vitamin B-12 supplementation is recommended.

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.

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.

Vanuit de hypothese dat griepvaccinatie residuele bescherming biedt tegen griepstammen die later kunnen circuleren, evalueerden we na 25 jaar de langetermijneffecten van een eenmalige griepvaccinatie. Daarvoor gebruikten we de gegevens van een gerandomiseerde placebogecontroleerde trial. Deze trial toonde aan dat griepvaccinatie griep kan voorkomen. Verder gebruikten we de follow-upgegevens van onder andere CBS en Gemeentelijke Basis-administratie om de totale sterfte en de sterfte aan cardiovasculaire of respiratoire oorzaken onder de trialdeelnemers na 25 jaar te berekenen. Met behulp van regressieanalyses bepaalden we de invloed van leeftijd en comorbiditeit op de langetermijnsterfte. Van 98% van de deelnemers konden we de vitale status op 1 januari 2017 achterhalen. In de groep als geheel was er geen aantoonbaar verschil in langetermijnsterfte tussen de interventiegroep (vaccinatie) en de controlegroep (placebo). Wel is er een mogelijk klinisch relevant effect op langetermijnsterfte bij jongere ouderen.

The effectiveness of influenza vaccination in the elderly has long been a topic of debate, fueled by the absence of direct evidence from randomized trials on its effect on mortality and the methodological limitations of observational studies pointing this direction. It is argued that new placebo-controlled trials should be undertaken to resolve this uncertainty. However, such trials may be ethically questionable. To bring this discussion forward, we provide a comprehensive overview of the ethical challenges of an influenza vaccine efficacy trial designed to evaluate mortality in the elderly. An important condition in the justification of a trial is the existence of genuine uncertainty in regard to the answer to a research question. Therefore an extensive analysis of the existing levels of knowledge is needed to support the conclusion that an effect of vaccination on mortality is uncertain. Even if a so called "clinical equipoise" status applies, denying a control group vaccination would be problematic because vaccination is considered "competent care" and withholding vaccination could substantially increase patients' risk for influenza and its complications. Given the high burden of disease and already proven benefits of vaccination, such a trial is unlikely to meet the Declaration of Helsinki stating that the importance of a trial must outweigh the risk patients are exposed to. While a placebo-controlled trial in vaccine refusers may be considered, such a trial is unlikely to meet substantial methodological barriers regarding trial size and generalizability. We conclude that a new trial is unlikely to provide for a direct answer, let alone change current policy. At the same time, given the lack of consensus on the ethical acceptability of a placebo-controlled trial on the effect of influenza vaccination on mortality in the elderly, we invite researchers considering such trials to address the ethical challenges discussed in this manuscript. (C) 2018 Elsevier Ltd. All rights reserved.

Background: It has been suggested that prenatal exposure to n-3 long-chain fatty acids protects against asthma and other allergy-related diseases later in childhood. The extent to which fish intake in pregnancy protects against child asthma and rhinitis symptoms remains unclear. We aimed to assess whether fish and seafood consumption in pregnancy is associated with childhood wheeze, asthma and allergic rhinitis. Methods: We pooled individual data from 60 774 mother-child pairs participating in 18 European and US birth cohort studies. Information on wheeze, asthma and allergic rhinitis prevalence was collected using validated questionnaires. The time periods of interest were: infancy (0-2 years), preschool age (3-4 years), and school age (5-8 years). We used multivariable generalized models to assess associations of fish and seafood (other than fish) consumption during pregnancy with child respiratory outcomes in cohort-specific analyses, with subsequent random-effects meta-analyses. Results: The median fish consumption during pregnancy ranged from 0.44 times/week in The Netherlands to 4.46 times/week in Spain. Maternal fish intake during pregnancy was not associated with offspring wheeze symptoms in any age group nor with the risk of child asthma [adjusted meta-analysis relative risk (RR) per 1-time/week = 1.01, 95% confidence interval 0.97-1.05)] and allergic rhinitis at school age (RR = 1.01, 0.99-1.03). These results were consistently found in further analyses by type of fish and seafood consumption and in sensitivity analyses. Conclusion: We found no evidence supporting a protective association of fish and seafood consumption during pregnancy with offspring symptoms of wheeze, asthma and allergic rhinitis from infancy to mid childhood. This work was supported by the European Community’s Seventh Framework Program [EU- FP7- HEALTH-2009-single-stage-241604]. Details of funding per cohort are available at IJE online.

ObjectiveTo investigate the associations of organic food consumption with maternal pre-pregnancy BMI, hypertension and diabetes in pregnancy, and several blood biomarkers of pregnant women.DesignProspective cohort study.SettingPregnant women were recruited at midwives’ practices and through channels related to consumption of food from organic origin.SubjectsPregnant women who filled in FFQ and donated a blood sample (n 1339). Participant groups were defined based on the share of consumed organic products; to discriminate between effects of food origin and food patterns, healthy diet indicators were considered in some statistical models.ResultsConsumption of organic food was associated with a more favourable pre-pregnancy BMI and lower prevalence of gestational diabetes. Compared with participants consuming no organic food (reference group), a marker of dairy products intake (pentadecanoic acid) and trans-fatty acids from natural origin (vaccenic and rumenic acids) were higher among participants consuming organic food (organic groups), whereas elaidic acid, a marker of the intake of trans-fatty acids found in industrially hydrogenated fats, was lower. Plasma levels of homocysteine and 25-hydroxyvitamin D were lower in the organic groups than in the reference group. Differences in pentadecanoic acid, vaccenic acid and vitamin D retained statistical significance when correcting for indicators of the healthy diet pattern associated with the consumption of organic food.ConclusionsConsumption of organic food during pregnancy is associated with several health-related characteristics and blood biomarkers. Part of the observed associations is explained by food patterns accompanying the consumption of organic food.

ObjectiveTo find out how the consumption of organic food during pregnancy is associated with consumer characteristics, dietary patterns and macro- and micronutrient intakes.DesignCross-sectional description of consumer characteristics, dietary patterns and macro- and micronutrient intakes associated with consumption of organic food during pregnancy.SettingHealthy, pregnant women recruited to a prospective cohort study at midwives’ practices in the southern part of the Netherlands; to enrich the study with participants adhering to alternative lifestyles, pregnant women were recruited through various specific channels.SubjectsParticipants who filled in questionnaires on food frequency in gestational week 34 (n 2786). Participant groups were defined based on the share of organic products within various food types.ResultsConsumers of organic food more often adhere to specific lifestyle rules, such as vegetarianism or anthroposophy, than do participants who consume conventional food only (reference group). Consumption of organic food is associated with food patterns comprising more products of vegetable origin (soya/vegetarian products, vegetables, cereal products, bread, fruits, and legumes) and fewer animal products (milk and meat), sugar and potatoes than consumed in conventional diets. These differences translate into distinct intakes of macro- and micronutrients, including higher retinol, carotene, tocopherol and folate intakes, lower intakes of vitamin D and B12 and specific types of trans-fatty acids in the organic groups. These differences are seen even in groups with low consumption of organic food.ConclusionsVarious consumer characteristics, specific dietary patterns and types of food intake are associated with the consumption of organic food during pregnancy.

Scope Understanding biological functions of different free human milk oligosaccharides (HMOs) in shaping gastrointestinal tract microbiota during infancy is of great interest. We examined a link between HMOs in maternal milk and infant faecal microbiota composition and investigated the role of microbiota in degrading HMOs within the GI tract of healthy, breastfed, one-month old infants. Methods and results Maternal breast milk and corresponding infant faeces originated from the KOALA Birth Cohort. HMOs were quantified in milk and infant faecal samples using PGC-UPLC-MS and HPAEC-PAD. Faecal microbiota composition was characterised using Illumina HiSeq amplicon 16S rRNA sequencing. The composition associated with gender, mode of delivery, and milk HMOs: Lacto-N-fucopentaose I and 2'-Fucosyllactose. Overall, Bifidobacterium, Bacteroides, Escherichia-Shigella and Parabacteroides were predominating genera. We detected three different patterns in the infant faecal microbiota structure. Gastrointestinal degradation of HMOs was strongly associated with faecal microbiota composition, and there was a link between utilisation of specific HMOs and abundance of various phylotypes (OTUs). Conclusions HMOs in maternal milk are among important factors shaping GI tract microbiota composition in one-month old breastfed infants. Infant's ability to metabolise different HMOs strongly correlate with faecal microbiota composition, and with phylotypes within genera Bifidobacterium, Bacteroides and Lactobacillus. This article is protected by copyright. All rights reserved.

Contains fulltext : 201327.pdf (Publisher’s version ) (Open Access) Gastrointestinal (GI) microbiota composition differs between breastfed and formula-fed infants. Today's infant formulas are often fortified with prebiotics to better mimic properties of human milk with respect to its effect on GI microbiota composition and function. We used Illumina HiSeq sequencing of PCR-amplified 16S rRNA gene fragments to investigate the composition of faecal microbiota in 2-12 week old infants receiving either breastmilk, infant formulas fortified with prebiotics, or mixed feeding. We compared these results with results from infants fed traditional formulas used in the Netherlands in 2002-2003, which contained no added prebiotics. We showed that today's formulas supplemented with either scGOS (0.24-0.50 g/100 ml) or scGOS and lcFOS (at a 9:1 ratio; total 0.6 g/100 ml) had a strong bifidogenic effect as compared to traditional formulas, and they also resulted in altered patterns of microbial colonisation within the developing infant gastrointestinal tract. We identified three microbial states (or developmental stages) in the first 12 weeks of life, with a gradual transition pattern towards a bifidobacteria dominated state. In infants receiving only fortified formulas, this transition towards the bifidobacteria dominated state was accelerated, whereas in infants receiving mixed feeding the transition was delayed, as compared to exclusively breastfed infants. 13 p.

Background The gut microbiota evolves from birth and is in early life influenced by events such as birth mode, type of infant feeding, and maternal and infant antibiotics use. However, we still have a gap in our understanding of gut microbiota development in older children, and to what extent early events and pre-school lifestyle modulate the composition of the gut microbiota, and how this impinges on whole body metabolic regulation in school-age children. Results Taking advantage of the KOALA Birth Cohort Study, a long-term prospective birth cohort in the Netherlands with extensive collection of high-quality host metadata, we applied shotgun metagenomics sequencing and systematically investigated the gut microbiota of children at 6–9 years of age. We demonstrated an overall adult-like gut microbiota in the 281 Dutch school-age children and identified 3 enterotypes dominated by the genera Bacteroides, Prevotella, and Bifidobacterium, respectively. Importantly, we found that breastfeeding duration in early life and pre-school dietary lifestyle correlated with the composition and functional competences of the gut microbiota in the children at school age. The correlations between pre-school dietary lifestyle and metabolic phenotypes exhibited a striking enterotype dependency. Thus, an inverse correlation between high dietary fiber consumption and low plasma insulin levels was only observed in individuals with the Bacteroides and Prevotella enterotypes, but not in Bifidobacterium enterotype individuals in whom the gut microbiota displayed overall lower microbial gene richness, alpha-diversity, functional potential for complex carbohydrate fermentation, and butyrate and succinate production. High total fat consumption and elevated plasma free fatty acid levels in the Bifidobacterium enterotype are associated with the co-occurrence of Streptococcus. Conclusions Our work highlights the persistent effects of breastfeeding duration and pre-school dietary lifestyle in affecting the gut microbiota in school-age children and reveals distinct compositional and functional potential in children according to enterotypes. The findings underscore enterotype-specific links between the host metabolic phenotypes and dietary patterns, emphasizing the importance of microbiome-based stratification when investigating metabolic responses to diets. Future diet intervention studies are clearly warranted to examine gut microbe-diet-host relationships to promote knowledge-based recommendations in relation to improving metabolic health in children. Electronic supplementary material The online version of this article (10.1186/s40168-018-0608-z) contains supplementary material, which is available to authorized users.

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.

ObjectiveMethodsThis study aimed to examine the intestinal microbiota composition of school-aged children in association with (over)weight.The fecal microbiota composition of 295 children was analyzed using the Human Intestinal Tract Chip. Anthropometric outcomes (overweight [BMI85th percentile], age- and sex-standardized BMI and weight z scores) were measured at 6 to 7 years of age, and elastic net was used to select genus-like bacterial groups related to all anthropometric outcomes. Subsequently, multiple linear and logistic regression models were used to model associations between selected bacterial groups and anthropometric measures while controlling for confounders.ResultsConclusionsPrevotella melaninogenica, Prevotella oralis, Dialister, and uncultured Clostridiales II (UCII) accounted for 26.1% of the variation in microbiota composition. Several bacterial groups were inversely associated with the anthropometric outcomes: Sutterella wadsworthensis, Marvinbryantia formatexigens, Prevotella melanogenica, P oralis, Burkholderia, uncultured Clostridiales II, and Akkermansia, while Streptococcus bovis was positively associated with overweight. Microbial diversity and richness, and Bacteroidetes to Firmicutes ratio, were not significantly associated with any of the outcomes.In the largest population-based study on childhood gut microbiota and body weight so far, both new and previously identified bacterial groups were found to be associated with overweight. Further research should elucidate their role in energy metabolism.

Background: Gestational diabetes and gestational hypertensive disorders are associated with offspring obesity, but the role of maternal adiposity in these associations remains unclear. We aimed to investigate whether these pregnancy complications affect the odds of offspring obesity independently of maternal obesity. Methods: We did an individual participant data (IPD) meta-analysis of mother–offspring pairs from prospective birth cohort studies that had IPD on mothers with singleton liveborn children born from 1989 onwards and had information available about maternal gestational diabetes, gestational hypertension or pre-eclampsia, and childhood body-mass index (BMI). We applied multilevel mixed-effects models to assess associations of gestational diabetes, gestational hypertension, and pre-eclampsia with BMI SD scores and the odds of overweight and obesity throughout childhood, adjusting for lifestyle characteristics (offspring's sex, maternal age, educational level, ethnicity, parity, and smoking during pregnancy). We then explored the extent to which any association was explained by maternal pre-pregnancy or early-pregnancy BMI. Findings: 160 757 mother–offspring pairs from 34 European or North American cohorts were analysed. Compared with uncomplicated pregnancies, gestational diabetes was associated with increased odds of overweight or obesity throughout childhood (odds ratio [OR] 1·59 [95% CI 1·36 to 1·86] for early childhood [age 2·0–4·9 years], 1·41 [1·26 to 1·57] for mid childhood [5·0–9·9 years], and 1·32 [0·97 to 1·78] for late childhood [10·0–17·9 years]); however, these associations attenuated towards the null following adjustment for maternal BMI (OR 1·35 [95% CI 1·15 to 1·58] for early childhood, 1·12 [1·00 to 1·25] for mid childhood, and 0·96 [0·71 to 1·31] for late childhood). Likewise, gestational hypertension was associated with increased odds of overweight throughout childhood (OR 1·19 [95% CI 1·01 to 1·39] for early childhood, 1·23 [1·15 to 1·32] for mid childhood, and 1·49 [1·30 to 1·70] for late childhood), but additional adjustment for maternal BMI largely explained these associations (1·01 [95% CI 0·86 to 1·19] for early childhood, 1·02 [0·95 to 1·10] for mid childhood, and 1·18 [1·03 to 1·36] for late childhood). Pre-eclampsia was associated with decreased BMI in early childhood only (difference in BMI SD score −0·05 SD score [95% CI −0·09 to −0·01]), and this association strengthened following additional adjustment for maternal BMI. Interpretation: Although lowering maternal risk of gestational diabetes, gestational hypertension, and pre-eclampsia is important in relation to maternal and fetal pregnancy outcomes, such interventions are unlikely to have a direct impact on childhood obesity. Preventive strategies for reducing childhood obesity should focus on maternal BMI rather than on pregnancy complications. Funding: EU's Horizon 2020 research and innovation programme (LifeCycle Project). This study has received support from the US National Institute of Health (R01 DK10324) and European Research Council under the European Union’s Seventh 22 Framework Programme (FP7/2007-2013) / ERC grant agreement no 669545. The Swedish Research Council, The Swedish Heart and Lung Foundation, The Swedish Research Council for Working Life and Social Welfare, the Swedish Asthma and Allergy Association Research Foundation, The Swedish Research Council Formas, Stockholm County Council, and the European Commission’s Seventh Framework 29 Program MeDALL under grant agreement No. 261357. This study has received support from the British Heart Foundation (CS/16/4/32482), 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. 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 EarlyNutrition under grant agreement n°289346, the European Union’s Horizon 2020 research and innovation programme under grant agreement No 633595 (DynaHEALTH) and the European Union’s Horizon 2020 research and innovation programme under grant agreement 733206 (LifeCycle Project). European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreements Early Nutrition n° 289346 and by funds from the Norwegian Research Council's MILPAAHEL programme, project No.213148. This study was funded by Grants from UE (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Spain: ISCIII (G03/176; FIS-FEDER: PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, 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). The "Rhea" project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-28.1.2.1.4 envirogenomarkers, EU FP7-HEALTH-2009- single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EU- FP7- HEALTH-2012 Proposal No 308333 HELIX) and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental 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). ROLO is supported by the Health Research Board Ireland, the Health Research Centre for Health and Diet Research, and the European Union's Seventh Framework Programme (FP7/2007-2013), project EarlyNutrition under grant agreement no. 289346. 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 (FP7/2007-2013), project EarlyNutrition (grant 289346). Study participants were drawn from a cohort study funded by the Medical Research Council and the Dunhill Medical Trust.

BackgroundOur knowledge of the role of parental and child-care staff behavior in the development and prevention of obesity is rapidly increasing. Potential interaction between both settings in socalled meso-systems, as hypothesized by the ecological systems perspective, is however often ignored. Specifically, inconsistency between home and child-care is hypothesized to have negative effects on child outcomes.MethodsParticipants were recruited through 23 child-care centers in the Netherlands. Data regarding 161 child-parent-child-care staff triads were available. Parenting and child care practices were assessed using validated questionnaires for parents (Child Feeding Practices Questionnaire, Preschooler Physical Activity Parenting Practices instrument) and child-care staff (Child-care Food and Activity Practices Questionnaire), using similar items in both settings. Absolute difference scores between parents and child-care staff were calculated for each triad as a measure of meso-system consistency. Child outcomes were physical activity (as assessed by accelerometry), dietary intake (from the parental questionnaire), and measured BMI z-scores. Paired t-tests were used to examine consistency between practices in both settings. Linear regression analyses were used to explore the association of parenting practices, child-care practices and difference scores on the one hand, and child outcomes on the other.ResultsSignificant differences between settings were found for almost all practices, and in most cases child-care staff scores more favorable on the practices than parents. Inconsistencies were mostly associated with unhealthy dietary intake and lower physical activity levels, but not with BMI.ConclusionThe current study showed that inconsistencies in parenting and child-care practices exist, and that these inconsistencies seem to be associated with unhealthy behavior in children. The results underline the importance of studying meso-system influences on behavior in general, and children's energy balance-related behavior specifically.

Vitamin D has immunomodulatory properties giving it the potential to affect microbial colonization of the intestinal tract. We investigated whether maternal vitamin D supplemention, maternal plasma 25-hydroxyvitamin D concentration, or direct supplementation of the infant influences key bacterial taxa within microbiota of one month old infants. Infant and maternal vitamin D supplement use was ascertained via questionnaires. Maternal plasma 25-hydroxyvitamin D was determined at approximately the 36th week of pregnancy. In 913 one month old infants in the prospective KOALA Birth Cohort Study, fecal Bifidobacterium spp., Escherichia coli, Clostridium difficile, Bacteroides fragilis group, Lactobacillus spp. and total bacteria were quantified with real-time polymerase chain reaction assays targeting 16S rRNA gene sequences. The association between vitamin D exposure and prevalence or abundance of a specific bacterial group or species was analyzed using logistic or linear regression, respectively. There was a statistically significant negative linear trend between counts of Bifidobacterium spp. and levels of maternal vitamin D supplementation and maternal 25-hydroxyvitamin D quintiles, respectively. In addition, a positive linear trend between quintile groups and B. fragilis group counts was observed. Lower counts of C. difficile were associated with vitamin D supplementation of breast fed infants whose mothers were more likely to adhere to an alternative lifestyle in terms of, e.g., dietary habits. These data suggest that vitamin D influences the abundance of several key bacterial taxa within the infant microbiota. Given that intestinal microbiotic homeostasis may be an important factor in the prevention of immune mediated diseases and that vitamin D status is a modifiable factor, further investigation of the impact of postnatal vitamin D supplementation should be conducted in older infants.

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.

The parallel epidemics of childhood asthma and obesity over the past few decades have spurred research into obesity as a risk factor for asthma. However, little is known regarding the role of asthma in obesity incidence. We examined whether early-onset asthma and related phenotypes are associated with the risk of developing obesity in childhood.This study includes 21 130 children born from 1990 to 2008 in Denmark, France, Germany, Greece, Italy, The Netherlands, Spain, Sweden and the UK. We followed non-obese children at 3-4 years of age for incident obesity up to 8 years of age. Physician-diagnosed asthma, wheezing and allergic rhinitis were assessed up to 3-4 years of age.Children with physician-diagnosed asthma had a higher risk for incident obesity than those without asthma (adjusted hazard ratio (aHR) 1.66, 95% CI 1.18-2.33). Children with active asthma (wheeze in the last 12 months and physician-diagnosed asthma) exhibited a higher risk for obesity (aHR 1.98, 95% CI 1.31-3.00) than those without wheeze and asthma. Persistent wheezing was associated with increased risk for incident obesity compared to never wheezers (aHR 1.51, 95% CI 1.08-2.09).Early-onset asthma and wheezing may contribute to an increased risk of developing obesity in later childhood. This work was partially supported by the Southern California Environmental Health Sciences Center (grant # P30ES007048) funded by the National Institute of Environmental Health Sciences [PI Gilliland]. Dr. Contreras was supported by a grant from the NIH T32ES013678. MEDALL and CHICOS Projects: The research leading to these results has received funding from the European Community’s Seventh Framework Program(Health–F2-grantagreements No. 261357 and 241604). Per cohort ABCD: Data of the Amsterdam Born Children and their Development cohort study used in this research was in part supported by funds from the Netherlands Organisation for Health Research and Development (ZonMw 40–00812-98–11010). The study sponsors had no role in study design, data analysis, interpretation of data, or writing of this report. BAMSE: We acknowledge all funding sources: The Swedish Research Council, The Swedish Heart and Lung Foundation, The Swedish Research Council for Working Life and Social Welfare, the Swedish Asthma and Allergy Association Research Foundation, The Swedish Research Council Formas, Stockholm County Council, and the European Commission’s Seventh Framework 29 Program Me DALL under grant agreement No.261357. We thank all the children and their parents for participating in the BAMSE cohort and the nurses and other staff members working in the BAMSE project. EDEN: We acknowledge all the funding sources for the EDEN study: Foundation for medical research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte santé 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 University, Nestlé, French National Institute for Population Health Surveillance (InVS),French National Institute for Health Education (INPES), the European Union FP7programmes (FP7/2007-2013, HELIX, ESCAPE, ENRIECO, Medall projects), Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients (AFD)), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l’Education Nationale a complementary health insurance (MGEN),French national agency for food security, French speaking association for the study ofdiabetes and metabolism (ALFEDIAM).We acknowledge the commitment of the EDEN mother-child cohort study group: I.Annesi-Maesano, JY. Bernard, J. Botton, M.A. Charles, P. Dargent-Molina, B. de Lauzon-Guillain, P. Ducimetière, M. de Agostini, B. Foliguet, , A. Forhan, X. Fritel, A. Germa, V.Goua, R. Hankard, B. Heude, M. Kaminski, B. Larroque†, N. Lelong, J. Lepeule, G.Magnin, L. Marchand, C. Nabet, F. Pierre, R. Slama, M.J. Saurel-Cubizolles, M.Schweitzer, O. Thiebaugeorges.The Generation R Study:The Generation R study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands Organisation for Scientific Research (NWO), the Ministry of Health, Welfareand Sport and the Ministry of Youth and Families. The project received funding from the European Union's Horizon 2020 research and innovation programme (LIFECYCLE project, grant agreement no 733206; 2016), the European Research Council (ERC-2014-CoG-648916) and from cofunded ERA-Net on Biomarkers for Nutrition and Health (ERAHDHL), Horizon 2020 (grant agreement no 696295; 2017), ZonMW The Netherlands (no529051014; 2017), Science Foundation Ireland (no SFI/16/ERA-HDHL/3360), and the European Union (ALPHABET project).The researchers are independent from the funders. The study sponsors had no role in study design, data analysis, interpretation of data, or writing of this report. INMA: Data used for this research was provided by the INMA-Environment and Childhood Project (www.proyectoinma.org). This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041), Spanish Ministry of Health (FIS-PIO41436, PI06/0867, PI081151, and FIS-FEDER 03/1615, 04/1112,04/1931, 05/1079, 05/1052, 06/1213, 07/0314 and 09/02647), Generalitat de Catalunya-CIRIT 1999SGR00241, the Conselleria de Sanitat Generalitat Valenciana, Department of Health of the Basque Government (2005111093 and 2009111069), the ProvincialGovernment of Gipuzkoa (DFG06/004 and DFG08/001).KOALA: The collection of the data from the KOALA Birth Cohort Study used in this analysis was financially supported by Friesland Foods (now Friesland Campina),Netherlands Asthma Foundation (grant numbers 3.2.07.022 and 3.2.03.48), Netherlands Heart Foundation (grant number 2014 T037, the Netherlands Organization for Health Research and Development (Zon Mw Prevention Program number 1.210-00-090), Triodos Foundation, Phoenix Foundation, Raphaël Foundation, Iona Foundation, Foundation forthe Advancement of Heilpedagogie, all in the Netherlands. MAS:The MAS birth cohort was funded by grants from the German Federal Ministry ofEducation and Research (BMBF; reference numbers 07015633, 07 ALE 27, 01EE9405/5,01EE9406) and the German Research Foundation (DFG; reference number KE 1462/2-1).PIAMA: The PIAMA study has been funded by The Netherlands Organisation for Health Research and Development; The Netherlands Organisation 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. RHEA: The Rhea project was financially supported by European projects (EU FP6-003-Food-3-NewGeneris -Contract No16320, EU FP6 STREP Hiwate -Contract No36224,EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers Contract No226756, EU FP7-HEALTH-2009-single stage CHICOS Contract No241604, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EU-FP7,Proposal No 264357 MeDALL, EU- FP7-HEALTH-2012 Proposal No 308333 HELIX),and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece:2011-2014; “Rhea Plus”: Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012-2015).ROBBIC: Data of the Rome cohort was in part supported byfunds from the Italian Ministry of Health (Programma speciale ex art. 12, comma 2, lettera b) del D. Lgs. 502/92,2001, 2003). We thank all the fields workers and the families for their contribution to thestudy. SWS: We thank the members of the Southampton Women's Survey Study group and the many participants in the SWS for their contribution to the study. The Southampton Women’s Survey is supported by grants from the Medical Research Council, British Heart Foundation, Food Standards Agency, British Lung Foundation, Arthritis Research UK, NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, and the European Union's Seventh Framework Programme (FP7/2007-2013), project Early Nutrition under grant agreement n°289346.

OBJECTIVE: To prospectively investigate the presence and counts of archaea in feces of 472 children in association with weight development from 6 to 10 years of age. METHODS: Within the KOALA Birth Cohort Study, a single fecal sample from each child was analyzed by quantitative polymerase chain reaction to quantify archaea (Methanobrevibacter smithii, Methanosphera stadtmanae). Anthropometric outcomes (overweight [body mass index {BMI} >/= 85th percentile], age- and sex-standardized BMI, weight, and height z-scores) were repeatedly measured at ages (mean +/- SD) of 6.2 +/- 0.5, 6.8 +/- 0.5, 7.8 +/- 0.5, and 8.8 +/- 0.5 years. Generalized estimating equation was used for statistical analysis while controlling for confounders. RESULTS: Methanobrevibacter smithii colonization was associated with an increased risk of overweight (adjusted odds ratio [OR] = 2.69; 95% confidence interval [CI] 0.96-7.54) from 6 to 10 years of age. Children with high levels (>7 log10 copies/g feces) of this archaeon were at highest risk for overweight (OR = 3.27; 95% CI 1.09-9.83). Moreover, M. smithii colonization was associated with higher weight z-scores (adj. beta 0.18; 95% CI 0.00-0.36), but not with height. For BMI z-scores, the interaction (P = 0.008) between M. smithii and age was statistically significant, implying children colonized with M. smithii had increasing BMI z-scores with age. CONCLUSIONS: Presence and higher counts of M. smithii in the gut of children are associated with higher weight z-scores, higher BMI z-scores, and overweight.