Association of picky eating around age 4 with dietary intake and weight status in early adulthood: A 14-year follow-up based on the KOALA birth cohort study.

INTRODUCTION: A relatively common deviant type of eating behaviour among children is picky eating. Research on associations between picky eating and dietary patterns later in life is limited, and studies examining long-term effects on growth have yielded mixed results. The present study aimed to examine longitudinal associations of picky eating in early childhood with consumption of various foods, and weight status (body mass index, BMI) in young adulthood. METHODS: Data from the Dutch KOALA Birth Cohort was used. Picky eating was determined around age 4 (range 3-6 years) by a questionnaire completed by parents. At follow-up around children's age 18 (range 17-20 years), weekly food intake frequencies, weight and height were assessed with a questionnaire completed by the grown-up young adult children. In total, 814 participants were included. Multiple regression analyses were performed for food intake frequencies and weight status (BMI) with picky eating score as predictor, controlling for parental and child covariates. RESULTS: The mean picky eating score at age 4-5 was 2.24 (range 1-5). A 1-point higher picky eating score was associated with eating fruit 0.14 days less per week, raw vegetables 0.14 days less per week, cooked vegetables 0.21 days less per week, fish 0.07 days less per week and dairy products 0.23 days less per week (P-values all <0.05). Associations between picky eating and intake frequencies of meat, eggs, various snacks, sweet drinks, and weight status (BMI) were not significant. CONCLUSION: Picky eating in childhood is associated with lower intake frequencies of various healthy foods among young adults. It is therefore recommended to pay sufficient attention to picky eating in young children.

Edge and modular significance assessment in individual-specific networks.

Individual-specific networks, defined as networks of nodes and connecting edges that are specific to an individual, are promising tools for precision medicine. When such networks are biological, interpretation of functional modules at an individual level becomes possible. An under-investigated problem is relevance or "significance" assessment of each individual-specific network. This paper proposes novel edge and module significance assessment procedures for weighted and unweighted individual-specific networks. Specifically, we propose a modular Cook's distance using a method that involves iterative modeling of one edge versus all the others within a module. Two procedures assessing changes between using all individuals and using all individuals but leaving one individual out (LOO) are proposed as well (LOO-ISN, MultiLOO-ISN), relying on empirically derived edges. We compare our proposals to competitors, including adaptions of OPTICS, kNN, and Spoutlier methods, by an extensive simulation study, templated on real-life scenarios for gene co-expression and microbial interaction networks. Results show the advantages of performing modular versus edge-wise significance assessments for individual-specific networks. Furthermore, modular Cook's distance is among the top performers across all considered simulation settings. Finally, the identification of outlying individuals regarding their individual-specific networks, is meaningful for precision medicine purposes, as confirmed by network analysis of microbiome abundance profiles.

Capturing the dynamics of microbial interactions through individual-specific networks.

Longitudinal analysis of multivariate individual-specific microbiome profiles over time or across conditions remains dauntin. Most statistical tools and methods that are available to study microbiomes are based on cross-sectional data. Over the past few years, several attempts have been made to model the dynamics of bacterial species over time or across conditions. However, the field needs novel views on handling microbial interactions in temporal analyses. This study proposes a novel data analysis framework, MNDA, that combines representation learning and individual-specific microbial co-occurrence networks to uncover taxon neighborhood dynamics. As a use case, we consider a cohort of newborns with microbiomes available at 6 and 9 months after birth, and extraneous data available on the mode of delivery and diet changes between the considered time points. Our results show that prediction models for these extraneous outcomes based on an MNDA measure of local neighborhood dynamics for each taxon outperform traditional prediction models solely based on individual-specific microbial abundances. Furthermore, our results show that unsupervised similarity analysis of newborns in the study, again using the notion of a taxon's dynamic neighborhood derived from time-matched individual-specific microbial networks, can reveal different subpopulations of individuals, compared to standard microbiome-based clustering, with potential relevance to clinical practice. This study highlights the complementarity of microbial interactions and abundances in downstream analyses and opens new avenues to personalized prediction or stratified medicine with temporal microbiome data.

Comparison of parent reported physician diagnosed asthma and general practitioner registration.

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.

Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children.

BACKGROUND: Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. METHODS: We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. RESULTS: Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. CONCLUSIONS: Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections.

Imbalanced Folate and Vitamin B12 in the Third Trimester of Pregnancy and its Association with Birthweight and Child Growth up to 2 Years.

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 µg day-1 combined with B12 < 5.5 µg day-1 ) are not associated with birthweight [ß 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 [ß 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 [ß adj = -7.10 (-97.90, 83.71) g]. Maternal dietary B12 intake [ß adj = -9.5 (-15.6, -3.3)] and plasma methylmalonic acid [ß 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.

Practical and Robust NMR-Based Metabolic Phenotyping of Gut Health in Early Life.

While substantial efforts have been made to optimize and standardize fecal metabolomics for studies in adults, the development of a standard protocol to analyze infant feces is, however, still lagging behind. Here, we present the development of a hands-on and robust protocol for proton 1H NMR spectroscopy of infant feces. The influence of extraction solvent, dilution ratio, homogenization method, filtration, and duration of centrifugation on the biochemical composition of infant feces was carefully evaluated using visual inspection of 1H NMR spectra in combination with multivariate statistical modeling. The optimal metabolomics protocol was subsequently applied on feces from seven infants collected at 8 weeks, 4, and 9 months of age. Interindividual variation was exceeding the variation induced by different fecal sample preparation methods, except for filtration. We recommend extracting fecal samples using water with a dilution ratio of 1:5 feces-to-water to homogenize using bead beating and to remove particulates using centrifugation. Samples collected from infants aged 8 weeks and 4 months showed elevated concentrations of milk oligosaccharide derivatives and lactic acid, whereas short-chain fatty acids (SCFAs) and branched-chain amino acids (BCAAs) were higher in the 9 month samples. The established protocol enables hands-on and robust analyses of the infant gut metabolome. The wide-ranging application of this protocol will facilitate interlaboratory comparison of infants' metabolic profiles and finally aid in a better understanding of infant gut health.

Infants' First Solid Foods: Impact on Gut Microbiota Development in Two Intercontinental Cohorts.

The introduction of solid foods is an important dietary event during infancy that causes profound shifts in the gut microbial composition towards a more adult-like state. Infant gut bacterial dynamics, especially in relation to nutritional intake remain understudied. Over 2 weeks surrounding the time of solid food introduction, the day-to-day dynamics in the gut microbiomes of 24 healthy, full-term infants from the Baby, Food & Mi and LucKi-Gut cohort studies were investigated in relation to their dietary intake. Microbial richness (observed species) and diversity (Shannon index) increased over time and were positively associated with dietary diversity. Microbial community structure (Bray-Curtis dissimilarity) was determined predominantly by individual and age (days). The extent of change in community structure in the introductory period was negatively associated with daily dietary diversity. High daily dietary diversity stabilized the gut microbiome. Bifidobacterial taxa were positively associated, while taxa of the genus Veillonella, that may be the same species, were negatively associated with dietary diversity in both cohorts. This study furthers our understanding of the impact of solid food introduction on gut microbiome development in early life. Dietary diversity seems to have the greatest impact on the gut microbiome as solids are introduced.

Maternal plasma choline and betaine in late pregnancy and child growth up to age 8 years in the KOALA Birth Cohort Study.

BACKGROUND: Sufficient choline and betaine during pregnancy are needed for fetal growth and development. OBJECTIVES: We aimed to investigate the associations between maternal plasma choline and betaine in the third trimester of pregnancy and child growth from birth up to 8 years of age. METHODS: Concentrations of choline and betaine were measured in plasma of 1331 pregnant women from the KOALA (Kind, Ouders en gezondheid: Aandacht voor Leefstijl en Aanleg) Birth Cohort Study in the Netherlands. Child weight and height were measured at birth and at 1 (91% complete), 2 (86%), and 6-8 y (76%). Birth weight, weight gain in the first year, and z scores for weight and height at 1 and 2 y were used as continuous outcome variables. BMI z scores at 1 and 2 y were used as continuous and dichotomous outcomes, and BMI z scores at age 6-8 y were used to study overweight at that age. RESULTS: Each 1-µmol/L increase of maternal plasma choline was associated with a mean 20-g (95% CI: 1.1, 38.0 g) higher weight gain in the first year of life, and a higher BMI z score (ß: 0.02; 95% CI: 0.00, 0.04) and slightly higher odds of BMI z score >85th percentile (OR: 1.08; 95% CI: 1.03, 1.10) at 1-2 y. Each 1-µmol/L increase of plasma betaine was associated with a mean 12-g (95% CI: 0.8, 23.9 g) higher weight gain in the first year of life and higher odds of BMI z score >85th percentile at 1-2 y (OR: 1.03; 95% CI: 1.00, 1.07). Lastly, betaine was associated with overweight at 6-8 y (OR: 1.17; 95% CI: 1.02, 1.34), only in boys. CONCLUSIONS: Third-trimester pregnancy plasma choline and betaine were positively associated with childhood anthropometric measures. In boys, some of the associations may have persisted up to 8 y of age. Further studies may investigate the validity of maternal plasma choline and betaine concentrations as markers of maternal intake and fetal transfer.

Investigating colonization patterns of the infant gut microbiome during the introduction of solid food and weaning from breastmilk: A cohort study protocol.

The first exposures to microbes occur during infancy and it is suggested that this initial colonization influences the adult microbiota composition. Despite the important role that the gut microbiome may have in health outcomes later in life, the factors that influence its development during infancy and early childhood have not been characterized fully. Guidelines about the introduction of solid foods and cessation of breastfeeding, which is thought to have a significant role in the transition to a more adult-like microbiota, are not based on microbiome research. There is even less understanding of approaches used to transition to solid food in the preterm population. The purpose of this study is to identify the impact of early life dietary events on gut microbiome community structures and function among infants born at term and pre-term. We plan to prospectively monitor the gut microbiome of infants during two critical timepoints in microbial development: the introduction of solid foods and cessation from breastmilk. A total of 35 participants from three primary observational birth cohorts (two full-term cohorts and one pre-term cohort) will be enrolled in this sub-study. Participants will be asked to collect stool samples and fill out a study diary before, during and after the introduction of solids and again during weaning from breastmilk. We will use frequent fecal sampling analyzed using 16S rRNA gene profiling, metagenomics, metabolomics, and targeted bacterial culturing to identify and characterize the microbial communities, as well as provide insight into the phenotypic characteristics and functional capabilities of the microbes present during these transitional periods of infancy. This study will provide a comprehensive approach to detailing the effects of dietary transition from breastmilk to a more adult-like solid food diet on the microbiome and in doing so will contribute to evidence-based infant nutrition guidance.

The Longitudinal Relationship Between Screen Time, Sleep and a Diagnosis of Attention-Deficit/Hyperactivity Disorder in Childhood.

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.

Changes in parental smoking during pregnancy and risks of adverse birth outcomes and childhood overweight in Europe and North America: An individual participant data meta-analysis of 229,000 singleton births.

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.

Physical activity and asthma development in childhood: Prospective birth cohort study.

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 ß, -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.

Association of Gestational Weight Gain With Adverse Maternal and Infant Outcomes.

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 <18.5); 133 788 (68.0%), normal weight (BMI, 18.5-24.9); 38 828 (19.7%), overweight (BMI, 25.0-29.9); 11 992 (6.1%), obesity grade 1 (BMI, 30.0-34.9); 3284 (1.7%), obesity grade 2 (BMI, 35.0-39.9); and 969 (0.5%), obesity grade 3 (BMI, ≥40.0). Overall, any adverse outcome occurred in 37.2% (n = 73 161) of women, ranging from 34.7% (2706 of 7809) among women categorized as underweight to 61.1% (592 of 969) among women categorized as obesity grade 3. Optimal gestational weight gain ranges were 14.0 kg to less than 16.0 kg for women categorized as underweight; 10.0 kg to less than 18.0 kg for normal weight; 2.0 kg to less than 16.0 kg for overweight; 2.0 kg to less than 6.0 kg for obesity grade 1; weight loss or gain of 0 kg to less than 4.0 kg for obesity grade 2; and weight gain of 0 kg to less than 6.0 kg for obesity grade 3. These gestational weight gain ranges were associated with low to moderate discrimination between those with and those without adverse outcomes (range for area under the receiver operating characteristic curve, 0.55-0.76). Results for discriminative performance in the validation sample were similar to the corresponding results in the main study sample (range for area under the receiver operating characteristic curve, 0.51-0.79). Conclusions and Relevance: In this meta-analysis of pooled individual participant data from 25 cohort studies, the risk for adverse maternal and infant outcomes varied by gestational weight gain and across the range of prepregnancy weights. The estimates of optimal gestational weight gain may inform prenatal counseling; however, the optimal gestational weight gain ranges had limited predictive value for the outcomes assessed.

Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood: An individual participant data meta-analysis.

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.

Intakes of Vitamin B-12 from Dairy Food, Meat, and Fish and Shellfish Are Independently and Positively Associated with Vitamin B-12 Biomarker Status in Pregnant Dutch Women.

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 <35 pmol/L and MMA >0.45 µmol/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 < 0.001]. The OR (95% CI) of vitamin B-12 deficiency in the third compared with the first tertile of dairy-derived vitamin B-12 was 0.13 (0.04, 0.49), and the ORs for vitamin B-12 from meat and fish were 0.33 (0.11, 0.97) and 0.25 (0.08, 0.82), respectively. Egg-derived vitamin B-12 was only associated with holoTC. Additional analyses showed that self-defined vegetarians and FFQ-defined lacto-ovo-vegetarians had lower median total dietary vitamin B-12 intake and considerably worse vitamin B-12 biomarker status than omnivores and pescatarians. 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.

Gestational weight gain charts for different body mass index groups for women in Europe, North America, and Oceania.

BACKGROUND: Gestational 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. METHODS: We 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. RESULTS: We observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40 weeks was 14.2 kg (11.4-17.4) for underweight women, 14.5 kg (11.5-17.7) for normal weight women, 13.9 kg (10.1-17.9) for overweight women, and 11.2 kg (7.0-15.7), 8.7 kg (4.3-13.4) and 6.3 kg (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. CONCLUSIONS: Gestational 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.

Gut Microbiota and Body Weight in School-Aged Children: The KOALA Birth Cohort Study.

OBJECTIVE: This study aimed to examine the intestinal microbiota composition of school-aged children in association with (over)weight. METHODS: The fecal microbiota composition of 295 children was analyzed using the Human Intestinal Tract Chip. Anthropometric outcomes (overweight [BMI  ≥  85th 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. RESULTS: Prevotella 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. CONCLUSIONS: 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.

Does early onset asthma increase childhood obesity risk? A pooled analysis of 16 European cohorts.

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.