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.

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 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.

Bidirectional associations between activity-related parenting practices, and child physical activity, sedentary screen-based behavior and body mass index: a longitudinal analysis.

BACKGROUND: It has been generally assumed that activity-related parenting practices influence children's activity behavior and weight status. However, vice versa parents may also change their parenting behaviors in response to their perceptions of their child's activity behavior and weight status. This study examined the bidirectional relationships between activity-related parenting practices, and physical activity, sedentary screen-based behavior, and body mass index (BMI) between children's age of 5 and 7 years. METHODS: Three scales of the Activity-related Parenting Questionnaire (i.e. 'restriction of sedentary behavior', 'stimulation of physical activity', and 'monitoring of physical activity') were completed by 1694 parents of the Dutch KOALA Birth Cohort Study at the child's age of around 5 and again around age 7. Physical activity, sedentary screen-based behavior and BMI were measured at both ages as well. Linear regression models were used to estimate the bidirectional associations between each parenting practice and the child's physical activity levels, sedentary screen-based behavior and BMI z-scores. RESULTS: Several parenting practices at age 5 predicted child physical activity, sedentary screen-based behavior, and BMI z-scores at age 7. Restriction of sedentary behavior positively predicted child BMI and sedentary screen-based behavior, whereas this practice negatively predicted child physical activity. In addition, stimulation of physical activity at age 5 was significantly associated with higher levels of child physical activity at age 7. The following child factors at age 5 predicted parenting practices at age 7: Child physical activity positively predicted parental stimulation of physical activity and monitoring activities. Sedentary screen-based behavior was associated with lower parental stimulation to be active. CONCLUSIONS: Findings generally revealed that parents and children mutually influence each other's behavior. A reinforcing feedback loop was present between parental stimulation of physical activity and child physical activity. Bidirectional parent-child interaction should be considered in future research in order to properly inform parenting-related intervention programs aimed at preventing or treating childhood overweight or obesity. System dynamic methods to explore the existence of reinforcing or balancing loops are needed in this regard.

Gut Colonization by Methanogenic Archaea Is Associated with Organic Dairy Consumption in Children.

The gut microbiota represents a complex and diverse ecosystem with a profound impact on human health, promoting immune maturation, and host metabolism as well as colonization resistance. Important members that have often been disregarded are the methanogenic archaea. Methanogenic archaea reduce hydrogen levels via the production of methane, thereby stimulating food fermentation by saccharolytic bacteria. On the other hand, colonization by archaea has been suggested to promote a number of gastrointestinal and metabolic diseases such as colorectal cancer, inflammatory bowel disease, and obesity. Archaea have been shown to be absent during infancy while omnipresent in school-aged children, suggesting that colonization may result from environmental exposure during childhood. The factors that determine the acquisition of methanogenic archaea, however, have remained undefined. Therefore, we aimed to explore determinants associated with the acquisition of the two main gastrointestinal archaeal species, Methanobrevibacter smithii and Methanosphaera stadtmanae, in children. Within the context of the KOALA Birth Cohort Study, fecal samples from 472 children aged 6-10 years were analyzed for the abundance of M. smithii and M. stadtmanae using qPCR. Environmental factors such as diet, lifestyle, hygiene, child rearing, and medication were recorded by repeated questionnaires. The relationship between these determinants and the presence and abundance of archaea was analyzed by logistic and linear regression respectively. Three hundred and sixty-nine out of the 472 children (78.2%) were colonized by M. smithii, and 39 out of the 472 children (8.3%) by M. stadtmanae. The consumption of organic yogurt (odds ratio: 4.25, CI95: 1.51; 11.95) and the consumption of organic milk (odds ratio: 5.58, CI95: 1.83; 17.01) were positively associated with the presence of M. smithii. We subsequently screened raw milk, processed milk, and yogurt samples for methanogens. We identified milk products as possible source for M. smithii, but not M. stadtmanae. In conclusion, M. smithii seems present in milk products and their consumption may determine archaeal gut colonization in children. For the first time, a large variety of determinants have been explored in association with gut colonization by methanogenic archaea. Although more information is needed to confirm and unravel the mechanisms in detail, it provides new insights on microbial colonization processes in early life.

Playability of school-environments and after-school physical activity among 8-11 year-old children: specificity of time and place.

BACKGROUND: Physical Activity (PA) occurs in several behavioral domains (e.g., sports, active transport), and is affected by distinct environmental factors. By filtering objective PA using children's school schedules, daily PA can be separated into more conceptually meaningful domains. We used an ecological design to investigate associations between "playability" of 21 school-environments and children's objectively measured after-school PA. We also examined to what extent distinct time-periods after-school and the distance from children's residence to their school influenced this association. METHODS: PA was measured in 587 8-11 year-old children by accelerometers, and separated in four two-hour time-periods after-school. For each school-environment, standardized playability-scores were calculated based on standardized audits within 800 m network buffers around each school. Schools and children's residences were geocoded, and we classified each child to be residing in 400, 800, 1600, or >1600 m crow-fly buffers from their school. The influence of network-distance buffers was also examined using the same approach. RESULTS: Playability was associated with light PA and moderate-to-vigorous PA after-school, especially in the time-period directly after-school and among children who lived within 800 m from their school. Playability explained approximately 30% of the after-school PA variance between schools. Greater distance from children's residence to their school weakened the association between playability of the school-environments and after-school PA. CONCLUSIONS: This study demonstrated that relationships between the conceptually matched physical environment and PA can be revealed and made plausible with increasing specificity in time and distance.

Food parenting practices and child dietary behavior. Prospective relations and the moderating role of general parenting.

Research on parenting practices has focused on individual behaviors while largely failing to consider the context of their use, i.e., general parenting. We examined the extent to which food parenting practices predict children's dietary behavior (classified as unhealthy: snacking, sugar-sweetened beverage; and healthy: water and fruit intake). Furthermore, we tested the moderating role of general parenting on this relationship. Within the KOALA Birth Cohort Study, in the Netherlands, questionnaire data were collected at 6 and 8 years (N = 1654). Correlations were computed to assess the association between food parenting practices and general parenting (i.e., nurturance, behavioral control, structure, coercive control, and overprotection). Linear regression models were fitted to assess whether food parenting practices predict dietary behavior. Instrumental and emotional feeding, and pressure to eat were found to have associations with undesirable child dietary behavior (increased unhealthy intake/decreased healthy intake), whereas associations were in the desirable direction for covert control, encouragement and restriction. Moderation analyses were performed by evaluating interactions with general parenting. The associations of encouragement and covert control with desirable child dietary behaviors were found to be stronger for children who were reared in a positive parenting context. Future research should assess the influence of contextual parenting factors moderating the relationships between food parenting and child dietary behavior as the basis for the development of more effective family-based interventions.

The next step in health behavior research: the need for ecological moderation analyses - an application to diet and physical activity at childcare.

BACKGROUND: The ecological perspective holds that human behavior depends on the interaction of different environmental factors and personal characteristics, but it lacks validation and operationalization. In the current paper, an ecological view was adopted to examine the interactive impact of several ecological systems on children's dietary intake and physical activity at childcare or similar facilities. The ecological view was operationalized into three types of interaction: 1) interaction between types of childcare environment (physical, social, political, economic); 2) interaction between micro-systems (the childcare and home environment) in meso-systems; and 3) interaction between childcare environment and child characteristics. The predictive value of each of these interactions was tested based on a systematic review of the literature. DISCUSSION: Several studies support the hypothesis that the influence of the childcare environment on children's physical activity and diet is moderated by child characteristics (age, gender), but interaction between environmental types as well as between micro-systems is hardly examined in the field of behavioral nutrition and physical activity. Qualitative studies and general child development research provide some valuable insights, but we advocate quantitative research adopting an ecological perspective on environmental influences. SUMMARY: Empirical studies operationalizing a true ecological view on diet and physical activity are scarce. Theorizing and assessment of interaction is advocated to become common practice rather than an exception in behavioral nutrition and physical activity research, in order to move the field forward.

Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes.

BACKGROUND: It has been hypothesized that a disturbed early lung development underlies the susceptibility to chronic obstructive pulmonary disease (COPD). Little is known about whether subjects genetically predisposed to COPD show their first symptoms or reduced lung function in childhood. OBJECTIVE: We investigated whether replicated genes for COPD associate with transient early wheeze (TEW) and lung function levels in 6- to 8-year-old children and whether cigarette smoke exposure in utero and after birth (environmental tobacco smoke [ETS]) modifies these effects. METHODS: The association of COPD-related genotypes of 20 single nucleotide polymorphisms in 15 genes with TEW, FEV1, forced vital capacity (FVC), and FEV1/FVC ratio was studied in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort (n = 1996) and replicated in the Child, parents and health: lifestyle and genetic constitution (KOALA) and Avon Longitudinal Study of Parents and Children (ALSPAC) cohorts. RESULTS: AGER showed replicated association with FEV1/FVC ratio. TNS1 associated with more TEW in PIAMA and lower FEV1 in ALSPAC. TNS1 interacted with ETS in PIAMA, showing lower FEV1 in exposed children. HHIP rs1828591 interacted with cigarette smoke exposure in utero in PIAMA and with ETS in ALSPAC, with lower lung function in nonexposed children. SERPINE2, FAM13A, and MMP12 associated with higher FEV1 and FVC, and SERPINE2, HHIP, and TGFB1 interacted with cigarette smoke exposure in utero in PIAMA only, showing adverse effects of exposure on FEV1 being limited to children with genotypes conferring the lowest risk of COPD. CONCLUSION: Our findings indicate relevant involvement of at least 3 COPD genes in lung development and lung growth by demonstrating associations pointing toward reduced airway caliber in early childhood. Furthermore, our results suggest that COPD genes are involved in the infant's lung response to smoke exposure in utero and in early life.

Influence of alternative lifestyles on self-reported body weight and health characteristics in women.

BACKGROUND: Alternative lifestyles are often associated with distinct practices with respect to nutrition, physical activity, smoking, alcohol use and usage of complementary medicine. Evidence concerning effects of these lifestyle-related practices on health status is still fragmentary. OBJECTIVE: To describe maternal health characteristics related to alternative lifestyles, with emphasis on body-weight status, during pregnancy and maternity periods. METHODS: We compared self-reported health-related features of mothers with alternative lifestyles and conventional lifestyles during pregnancy and maternity period in the KOALA Birth Cohort Study. This cohort comprises two recruitment groups of mother-infant pairs, one with a conventional (no selection based on lifestyle, n = 2333), the other with an alternative lifestyle (selected via organic food shops, anthroposophic clinicians and midwives, anthroposophic under-five clinics, Rudolf Steiner schools and relevant magazines, n = 485). Mothers in the alternative group more frequently chose organic foods, adhered to specific living rules, practised vegetarianism and identified themselves with anthroposophy. RESULTS: Mothers in the alternative group showed lower BMI and lower prevalence of overweight and obesity than the conventional group, before pregnancy as well as 4-5 years after delivery. This difference was partly retained after adjusting for potential confounders. Furthermore, women in the alternative group had a lower prevalence of pregnancy-related hypertension, more often started breastfeeding and gave exclusive and prolonged breastfeeding for a longer period. Finally, they smoked less often, but more often drunk alcohol during pregnancy. CONCLUSION: The results suggest that an alternative lifestyle is associated with favourable body weight and with several differences in other health features.

Clustering of energy balance-related behaviors in 5-year-old children: lifestyle patterns and their longitudinal association with weight status development in early childhood.

BACKGROUND: This study identified lifestyle patterns by examining the clustering of eating routines (e.g. eating together as a family, having the television on during meals, duration of meals) and various activity-related behaviors (i.e. physical activity (PA) and sedentary screen-based behavior) in 5-year-old children, as well as the longitudinal association of these patterns with weight status (BMI and overweight) development up to age 8. METHODS: Data originated from the KOALA Birth Cohort Study (N = 2074 at age 5). Principal component analysis (PCA) was used to identify lifestyle patterns. Backward regression analyses were used to examine the association of lifestyle patterns with parent and child background characteristics, as well as the longitudinal associations between the patterns and weight status development. RESULTS: Four lifestyle patterns emerged from the PCA: a 'Television-Snacking' pattern, a 'Sports-Computer' pattern, a 'Traditional Family' pattern, and a "Fast' Food' pattern. Child gender and parental educational level, working hours and body mass index were significantly associated with the scores for the patterns. The Television-Snacking pattern was positively associated with BMI (standardized regression coefficient ß = 0.05; p < 0.05), and children with this pattern showed a positive tendency toward being overweight at age 8 (Odds ratio (OR) = 1.27, p = 0.06). In addition, the Sports-Computer pattern was significantly positively associated with an increased risk of becoming overweight at age 7 (OR = 1.28, p < 0.05). CONCLUSIONS: The current study showed the added value of including eating routines in cross-behavioral clustering analyses. The findings indicate that future interventions to prevent childhood overweight should address eating routines and activity/inactivity simultaneously, using the synergy between clustered behaviors (e.g. between television viewing and snacking).

European birth cohorts for environmental health research.

BACKGROUND: Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning. OBJECTIVES: Our goal was to create a comprehensive overview of European birth cohorts with environmental exposure data. METHODS: Birth cohort studies were included if they a) collected data on at least one environmental exposure, b) started enrollment during pregnancy or at birth, c) included at least one follow-up point after birth, d) included at least 200 mother-child pairs, and e) were based in a European country. A questionnaire collected information on basic protocol details and exposure and health outcome assessments, including specific contaminants, methods and samples, timing, and number of subjects. A full inventory can be searched on www.birthcohortsenrieco.net. RESULTS: Questionnaires were completed by 37 cohort studies of > 350,000 mother-child pairs in 19 European countries. Only three cohorts did not participate. All cohorts collected biological specimens of children or parents. Many cohorts collected information on passive smoking (n = 36), maternal occupation (n = 33), outdoor air pollution (n = 27), and allergens/biological organisms (n = 27). Fewer cohorts (n = 12-19) collected information on water contamination, ionizing or nonionizing radiation exposures, noise, metals, persistent organic pollutants, or other pollutants. All cohorts have information on birth outcomes; nearly all on asthma, allergies, childhood growth and obesity; and 26 collected information on child neurodevelopment. CONCLUSION: Combining forces in this field will yield more efficient and conclusive studies and ultimately improve causal inference. This impressive resource of existing birth cohort data could form the basis for longer-term and worldwide coordination of research on environment and child health.

General parenting, childhood overweight and obesity-inducing behaviors: a review.

Despite emerging efforts to investigate the influence parents have on their children's weight status and related dietary and activity behaviors, reviews regarding the role of general parenting are lacking. We performed a systematic review regarding the relationship between general parenting and these weight-related outcomes to guide observational research. In total, 36 studies were included. Discrepancies across studies were found, which may be explained by differences in conceptualization of parenting constructs. Overall, however, results suggest that children raised in authoritative homes ate more healthy, were more physically active and had lower BMI levels, compared to children who were raised with other styles (authoritarian, permissive/indulgent, uninvolved/neglectful). Findings of some moderation studies indicate that general parenting has a differential impact on children's weight-related outcomes, depending on child and parental characteristics. These findings underline the importance of acknowledging interactions between general parenting and both child and parent characteristics, as well as behavior-specific parenting practices.

Gene-gene interaction in regulatory T-cell function in atopy and asthma development in childhood.

BACKGROUND: Regulatory T-cell dysfunction is associated with development of the complex genetic conditions atopy and asthma. Therefore, we hypothesized that single nucleotide polymorphisms in genes involved in the development and function of regulatory T cells are associated with atopy and asthma development. OBJECTIVE: To evaluate main effects and gene-gene interactions of haplotype tagging single nucleotide polymorphisms of genes involved in regulatory T-cell function-IL6, IL6R, IL10, heme-oxygenase 1 (HMOX1), IL2, Toll-like receptor 2 (TLR2), TGFB1, TGF-beta receptor (TGFBR)-1, TGFBR2, IL2RA, and forkhead box protein 3 (FOXP3)-in relation to atopy and asthma. METHODS: Single-locus and multilocus associations with total IgE (3rd vs 1st tertile); specific IgE to egg, milk, and indoor allergens; and asthma were evaluated by chi(2) tests and the multifactor dimensionality-reduction method in 3 birth cohorts (Allergenic study). RESULTS: Multiple statistically significant multilocus associations existed. IL2RA rs4749926 and TLR2 rs4696480 associated with IgE in both age groups tested (1-2 and 6-8 years). TGFBR2 polymorphisms associated with total and specific IgE in both age groups and with asthma. TGFBR2 rs9831477 associated with specific IgE for milk at age 1 to 2 years and indoor allergens at age 6 to 8 years. For milk-specific IgE, interaction between TGFBR2 and FOXP3 polymorphisms was confirmed by logistic regression and consistent in 2 birth cohorts and when stratified for sex, supplying internal replications. CONCLUSION: Genes involved in the development and function of regulatory T cells, specifically IL2RA, TLR2, TGFBR2, and FOXP3, associate with atopy and asthma by gene-gene interaction. Modeling of multiple gene-gene interactions is important to unravel further the genetic susceptibility to atopy and asthma.

Clustering of dietary intake and sedentary behavior in 2-year-old children.

OBJECTIVE: To examine clustering of energy balance-related behaviors (EBRBs) in young children. This is crucial because lifestyle habits are formed at an early age and track in later life. This study is the first to examine EBRB clustering in children as young as 2 years. STUDY DESIGN: Cross-sectional data originated from the Child, Parent and Health: Lifestyle and Genetic Constitution (KOALA) Birth Cohort Study. Parents of 2578 2-year-old children completed a questionnaire. Correlation analyses, principal component analyses, and linear regression analyses were performed to examine clustering of EBRBs. RESULTS: We found modest but consistent correlations in EBRBs. Two clusters emerged: a "sedentary-snacking cluster" and a "fiber cluster." Television viewing clustered with computer use and unhealthy dietary behaviors. Children who frequently consumed vegetables also consumed fruit and brown bread more often and white bread less often. Lower maternal education and maternal obesity were associated with high scores on the sedentary-snacking cluster, whereas higher educational level was associated with high fiber cluster scores. CONCLUSIONS: Obesity-prone behavioral clusters are already visible in 2-year-old children and are related to maternal characteristics. The findings suggest that obesity prevention should apply an integrated approach to physical activity and dietary intake in early childhood.

Association of interacting genes in the toll-like receptor signaling pathway and the antibody response to pertussis vaccination.

BACKGROUND: Activation of the Toll-like receptor (TLR) signaling pathway through TLR4 may be important in the induction of protective immunity against Bordetella pertussis with TLR4-mediated activation of dendritic and B cells, induction of cytokine expression, and reversal of tolerance as crucial steps. We examined whether single nucleotide polymorphisms (SNPs) in genes of the TLR4 pathway and their interaction are associated with the response to whole-cell vaccine (WCV) pertussis vaccination in 490 one-year-old children. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed associations of 75 haplotype-tagging SNPs in genes in the TLR4 signaling pathway with pertussis toxin (PT)-IgG titers. We found significant associations between the PT-IgG titer and SNPs in CD14, TLR4, TOLLIP, TIRAP, IRAK3, IRAK4, TICAM1, and TNFRSF4 in one or more of the analyses. The strongest evidence for association was found for two SNPs (rs5744034 and rs5743894) in TOLLIP that were almost completely in linkage disequilibrium, provided statistically significant associations in all tests with the lowest p-values, and displayed a dominant mode of inheritance. However, none of these single gene associations would withstand correction for multiple testing. In addition, Multifactor Dimensionality Reduction Analysis, an approach that does not need correction for multiple testing, showed significant and strong two and three locus interactions between SNPs in TOLLIP (rs4963060), TLR4 (rs6478317) and IRAK1 (rs1059703). CONCLUSIONS/SIGNIFICANCE: We have identified significant interactions between genes in the TLR pathway in the induction of vaccine-induced immunity. These interactions underline that these genes are functionally related and together form a true biological relationship in a protein-protein interaction network. Practically all our findings may be explained by genetic variation in directly or indirectly interacting proteins at the extra- and intracytoplasmic sites of the cell membrane of antigen-presenting cells, B cells, or both. Fine tuning of interacting proteins in the TLR pathway appears important for the induction of an optimal vaccine response.

Etiology of atopy in infancy: the KOALA Birth Cohort Study.

The aim of the KOALA Birth Cohort Study in the Netherlands is to identify factors that influence the clinical expression of atopic disease with a main focus on lifestyle (e.g., anthroposophy, vaccinations, antibiotics, dietary habits, breastfeeding and breast milk composition, intestinal microflora composition, infections during the first year of life, and gene-environment interaction). The recruitment of pregnant women started in October 2000. First, participants with 'conventional lifestyles' (n = 2343) were retrieved from an ongoing prospective cohort study (n = 7020) on pregnancy-related pelvic girdle pain. In addition, pregnant women (n = 491) with 'alternative lifestyles' with regard to child rearing practices, dietary habits (organic, vegetarian), vaccination schemes and/or use of antibiotics, were recruited through organic food shops, anthroposophic doctors and midwives, Steiner schools, and dedicated magazines. All participants were enrolled between 14 and 18 wk of gestation and completed an intake questionnaire on family history of atopy and infant care intentions. Documentation of other relevant variables started in the pregnant mother and covered the first and third trimester as well as early childhood by repeated questionnaires at 14-18, 30, and 34 wk of gestation and 3, 7, 12, and 24 months post-partum. A subgroup of participants, including both conventional and alternative lifestyles, was asked to consent to maternal blood sampling, breast milk and a faecal sample of the infant at 1 month post-partum, capillary blood at age 1 yr, venous blood and observation of manifestation of atopic dermatitis during home visits at the age of 2 yr (using the UK working party criteria and the severity scoring of atopic dermatitis index), and buccal swabs for DNA isolation from child-parent trios. From the start, ethical approval and informed consent procedures included gene-environment interaction studies. Follow-up at 3 and 7 months post-partum was completed with high response rates (respectively 90% and 88% in the conventional group, and 97% and 97% in the alternative group). The home visits at 2 yr of age will be completed in 2005. Preliminary results show that we have succeeded in recruiting a large population with various lifestyle choices with a fairly large contrast with regard to dietary habits (including organic foods, vegetarian diet), vaccination schemes and/or use of antibiotics. We have also been able to collect a large number of faecal samples (n = 1176) and capillary blood samples at age 1 yr (n = 956). Furthermore, a large proportion of the participants have consented with genetic studies. Mid 2006 we expect to report our first results on the relationship between the various exposures in early life and childhood atopy. An outline of the focus and design of the KOALA Birth Cohort Study is presented.

The behavioral determinants of breast-feeding in The Netherlands: predictors for the initiation of breast-feeding.

The aim of this study was to evaluate the behavioral determinants of the initiation of breast-feeding at birth. The prospective cohort study used the attitude, social influence, self-efficacy (ASE) model in 373 pregnant women in five child health care centers. Prenatally, 72% of the women had the intention to breast-feed, and 73% actually started with breast-feeding at birth. Mothers who initiated breast-feeding differed in almost all the attitude, social influence, and self-efficacy determinants from others who initiated formula feeding. Intention was a very strong predictor of the initiation of breast-feeding. The components of the ASE model predicted the initiation of breast-feeding. Hence, the results may be used to tailor future interventions aimed at promoting breast-feeding.