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.

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.

Non-Cholesterol Sterols in Breast Milk and Risk of Allergic Outcomes in the First Two Years of Life.

This study aimed to explore associations between non-cholesterol sterol concentrations in breast milk and allergic outcomes in children aged two. Data from the KOALA Birth Cohort Study, the Netherlands, were used. Non-cholesterol sterols were analyzed by gas-liquid chromatography-mass spectrometry in breast milk sampled one-month postpartum (N = 311). Sterols were selected for each allergic outcome, i.e., eczema, wheeze, and allergic sensitization, prior to analyses. Associations between the selected sterols with allergic outcomes were analyzed using multiple logistic regression to calculate odds ratios (ORs). The odds of eczema in the first two years of life were lower with higher concentrations of cholestanol (OR (95%CI): 0.98 (0.95; 1.00), p = 0.04), lanosterol (0.97 (0.95; 1.00), p = 0.02), lathosterol (0.93 (0.87; 0.99), p = 0.02), and stigmasterol (0.51 (0.29; 0.91), p = 0.02) in breast milk sampled one-month postpartum. None of the sterols were associated with wheeze in the first two years of life. The odds of allergic sensitization at age two were lower with higher concentrations of campesterol in breast milk (OR (95%CI): 0.81 (0.70; 0.95), p = 0.01). In conclusion, our data suggest that exposure to higher non-cholesterol sterol concentrations in breast milk may indeed be associated with the prevention of allergic outcomes in the first two years of life.

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.

Association between COVID-19 Primary Vaccination and Severe Disease Caused by SARS-CoV-2 Delta Variant among Hospitalized Patients: A Belgian Retrospective Cohort Study.

We aimed to investigate vaccine effectiveness against progression to severe COVID-19 (acute respiratory distress syndrome (ARDS), intensive care unit (ICU) admission and/or death) and in-hospital death in a cohort of hospitalized COVID-19 patients. Mixed effects logistic regression analyses were performed to estimate the association between receiving a primary COVID-19 vaccination schedule and severe outcomes after adjusting for patient, hospital, and vaccination characteristics. Additionally, the effects of the vaccine brands including mRNA vaccines mRNA-1273 and BNT162b2, and adenovirus-vector vaccines ChAdOx1 (AZ) and Ad26.COV2.S (J&J) were compared to each other. This retrospective, multicenter cohort study included 2493 COVID-19 patients hospitalized across 73 acute care hospitals in Belgium during the time period 15 August 2021-14 November 2021 when the Delta variant (B1.617.2) was predominant. Hospitalized COVID-19 patients that received a primary vaccination schedule had lower odds of progressing to severe disease (OR (95% CI); 0.48 (0.38; 0.60)) and in-hospital death (OR (95% CI); 0.49 (0.36; 0.65)) than unvaccinated patients. Among the vaccinated patients older than 75 years, mRNA vaccines and AZ seemed to confer similar protection, while one dose of J&J showed lower protection in this age category. In conclusion, a primary vaccination schedule protects against worsening of COVID-19 to severe outcomes among hospitalized patients.

Influence of Alternative Lifestyles on Antibiotic Use during Pregnancy, Lactation and in Children.

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.

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.

Organic food use, meat intake, and prevalence of gestational diabetes: KOALA birth cohort study.

PURPOSE: To evaluate whether consumption of organic food and reduced intake of meat products in pregnancy are associated with lower prevalence of gestational diabetes (GD). METHODS: Women participating in the KOALA Birth Cohort Study with valid informed consent, a singleton pregnancy and information on their food intake were considered in this cross-sectional analysis. Participants with and without GD were compared with each other in terms of dietary characteristics (n = 37 and n = 2766, respectively). Multivariable logistic regression (LR) was used to adjust for relevant covariates. RESULTS: Organic food consumption tended to be lower, although not significantly, in women with GD compared to women without GD, whereas consumption of meat was positively associated with GD prevalence. LR modelling showed that GD was significantly associated with higher consumption of meat and, in addition, also of cheese, after adjustment for other relevant covariates. GD was associated with some indicators of animal product intake, namely dietary animal to plant protein ratio and maternal plasma arachidonic acid (for the latter, data available for n = 16 and n = 1304, respectively). Food patterns of participants with GD were characterised by more meat products and less vegetarian products. CONCLUSIONS: Due to the low number of participants with GD, results have to be interpreted cautiously. Consumption of organic food during pregnancy does not seem to be markedly associated with a lower GD prevalence; lower intake of meat and cheese, irrespective of its origin (organic or conventional), does. The latter supports previous studies suggesting a causal association between consumption of animal products and GD.

Combining HPAEC-PAD, PGC-LC-MS, and 1D 1H NMR to Investigate Metabolic Fates of Human Milk Oligosaccharides in 1-Month-Old Infants: a Pilot Study.

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.

Breast milk n-3 long-chain polyunsaturated fatty acids and blood pressure: an individual participant meta-analysis.

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.

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.

Investigating longitudinal context-specific physical activity patterns in transition from primary to secondary school using accelerometers, GPS, and GIS.

INTRODUCTION: Previous longitudinal studies indicate that physical activity (PA) significantly declines from primary-to secondary school, and report both changes in individual and environmental determinants of PA. In order to understand this transition and to prevent this negative trend, it is important to gather contextually rich data on possible mechanisms that drive this decline. Therefore, the aim of this study was to investigate changes of PA patterns in transition between primary and secondary school, and to add domain-specific insights of how, where, and when these changes occur. METHODS: In total, 175 children participated in a 7-day accelerometer- and Global Positioning System (GPS) protocol at their last year of primary and their first year of secondary school. GPS data-points were overlaid with Geographical Information Systems (GIS) data using ArcGIS 10.1 software. Based on the GPS locations of individual data-points, we identified child's PA at home, school, local sports grounds, shopping centers, and other locations. Also, trips in active and passive transport were identified according to previously validated GPS speed-algorithms. Longitudinal multi-level linear mixed models were fitted adjusting for age, gender, meteorological circumstances, and the nested structure of days within children and children within schools. Outcome measures were minutes spent in light PA and moderate-to-vigorous PA, specified for the time-segments before school, during school, after school and weekend days. RESULTS: Total PA significantly declined from primary to secondary school. Although transport-related PA increased before- and during school, decreases were found for especially afterschool time spent at sports grounds and transport-related PA during weekends. CONCLUSIONS: This is the first study that demonstrated longitudinal changes of context- and domain-specific PA patterns in transition between primary and secondary school, based on device-assessed PA. Given the importance of this transition-period for the development of long-term PA patterns, results from this study warrant the development of evidence-based PA programs in this transition period, while acknowledging the integrative role of schools, parents, and afterschool sports providers. More specifically, the results underline the need to increase children's PA levels in primary schools, promote afterschool PA at secondary schools, and to prevent the drop-out in sports participation at secondary schools.

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.

Critical Hours and Important Environments: Relationships between Afterschool Physical Activity and the Physical Environment Using GPS, GIS and Accelerometers in 10-12-Year-Old Children.

INTRODUCTION: The objective of this study was to assess relationships between children's physical environment and afterschool leisure time physical activity (PA) and active transport. METHODS: Children aged 10-12 years participated in a 7-day accelerometer and Global Positioning Systems (GPS) protocol. Afterschool leisure time PA and active transport were identified based on location- and speed-algorithms based on accelerometer, GPS and Geospatial Information Systems (GIS) data. We operationalized children's exposure to the environment by combining home, school and the daily transport environment in individualized daily activity-spaces. RESULTS: In total, 255 children from 20 Dutch primary schools from suburban areas provided valid data. This study showed that greenspaces and smaller distances from the children's home to school were associated with afterschool leisure time PA and walking. Greater distances between home and school, as well as pedestrian infrastructure were associated with increased cycling. CONCLUSION: We demonstrated associations between environments and afterschool PA within several behavioral contexts. Future studies are encouraged to target specific behavioral domains and to develop natural experiments based on interactions between several types of the environment, child characteristics and potential socio-cognitive processes.

Influenza vaccination in the elderly: 25 years follow-up of a randomized controlled trial. No impact on long-term mortality.

Influenza vaccination is proven effective in preventing influenza. However, long-term effects on mortality have never been supported by direct evidence. In this study we assessed the long-term outcome of influenza vaccination on mortality in the elderly by conducting a 25-year follow-up study of a RCT on the efficacy of influenza vaccination as baseline. The RCT had been conducted in the Netherlands 5 years before vaccination was recommended for those aged >65 and 17 years before recommending it for those aged >60. The RCT included 1838 community-dwelling elderly aged ≥ 60 that had received an intramuscular injection with the inactivated quadrivalent influenza vaccine (n = 927) or placebo (n = 911) during the 1991/1992 winter. In our follow-up study, outcomes included all-cause mortality, influenza-related mortality and seasonal mortality. Unadjusted and adjusted hazard ratios (HRs) were estimated by Cox regression and sub-hazard ratios (SHRs) by competing risk models. Secondary analyses included subgroup analyses by age and disease status. The vital status up to January 1, 2017 was provided in 1800/1838 (98%) of the cases. Single influenza vaccination did not reduce all-cause mortality when compared to placebo (adjusted HR 0.95, 95% CI 0.85-1.05). Also, no differences between vaccination and placebo group were shown for underlying causes of death or seasonal mortality. In those aged 60-64, median survival increased with 20.1 months (95% CI 2.4-37.9), although no effects on all-cause mortality (adjusted HR 0.86, 95% CI 0.72-1.03) could be demonstrated in survival analysis. In conclusion, this study did not demonstrate a statistically significant effect following single influenza vaccination on long-term mortality in community-dwelling elderly in general. We propose researchers designing future studies on influenza vaccination in the elderly to fit these studies for longer-term follow-up, and suggest age-group comparisons in observational research. Clinical trial registry number: NTR6179.

Correlating Infant Fecal Microbiota Composition and Human Milk Oligosaccharide Consumption by Microbiota of 1-Month-Old Breastfed Infants.

SCOPE: Understanding the biological functions of human milk oligosaccharides (HMOs) in shaping gastrointestinal (GI) tract microbiota during infancy is of great interest. A link between HMOs in maternal milk and infant fecal microbiota composition is examined and the role of microbiota in degrading HMOs within the GI tract of healthy, breastfed, 1-month-old infants is investigated. METHODS AND RESULTS: Maternal breast milk and infant feces are from the KOALA Birth Cohort. HMOs are quantified in milk and infant fecal samples using liquid chromatography-mass spectrometry. Fecal microbiota composition is characterized using Illumina HiSeq 16S rRNA gene amplicon sequencing. The composition is associated with gender, delivery mode, and milk HMOs: Lacto-N-fucopentaose I and 2'-fucosyllactose. Overall, Bifidobacterium, Bacteroides, Escherichia-Shigella, and Parabacteroides are predominating genera. Three different patterns in infant fecal microbiota structure are detected. GI degradation of HMOs is strongly associated with fecal microbiota composition, and there is a link between utilization of specific HMOs and relative abundance of various phylotypes (operational taxonomic units). CONCLUSIONS: HMOs in maternal milk are among the important factors shaping GI tract microbiota in 1-month-old breastfed infants. An infant's ability to metabolize different HMOs strongly correlates with fecal microbiota composition and specifically with phylotypes within genera Bifidobacterium, Bacteroides, and Lactobacillus.

The effect of prebiotic fortified infant formulas on microbiota composition and dynamics in early life.

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.

Impact of early events and lifestyle on the gut microbiota and metabolic phenotypes in young school-age children.

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.

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.