Maternal smoking during pregnancy increases the risk of gut microbiome-associated childhood overweight and obesity.

Childhood obesity is linked to maternal smoking during pregnancy. Gut microbiota may partially mediate this association and could be potential targets for intervention; however, its role is understudied. We included 1,592 infants from the Canadian Healthy Infants Longitudinal Development Cohort. Data on environmental exposure and lifestyle factors were collected prenatally and throughout the first three years. Weight outcomes were measured at one and three years of age. Stool samples collected at 3 and 12 months were analyzed by sequencing the V4 region of 16S rRNA to profile microbial compositions and magnetic resonance spectroscopy to quantify the metabolites. We showed that quitting smoking during pregnancy did not lower the risk of offspring being overweight. However, exclusive breastfeeding until the third month of age may alleviate these risks. We also reported that maternal smoking during pregnancy significantly increased Firmicutes abundance and diversity. We further revealed that Firmicutes diversity mediates the elevated risk of childhood overweight and obesity linked to maternal prenatal smoking. This effect possibly occurs through excessive microbial butyrate production. These findings add to the evidence that women should quit smoking before their pregnancies to prevent microbiome-mediated childhood overweight and obesity risk, and indicate the potential obesogenic role of excessive butyrate production in early life.

Pre-labor and post-labor cesarean delivery and early childhood adiposity in the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study.

BACKGROUND/OBJECTIVES: Delivery by cesarean section (CS) compared to vaginal delivery has been associated with increased risk of overweight in childhood. Our study examined if the presence or absence of labor events in CS delivery altered risk of overweight in early childhood (1-5 years) compared to vaginal delivery and if this association differed according to infant sex. SUBJECTS/METHODS: The study included 3073 mother-infant pairs from the CHILD Cohort Study in Canada. Data from birth records were used to categorize infants as having been vaginally delivered, or delivered by CS, with or without labor events. Age and sex adjusted weight-for-length (WFL) and body mass index (BMI) z scores were calculated from height and weight data from clinic visits at 1, 3 and 5 years and used to classify children as overweight. Associations between delivery mode and child overweight at each timepoint were assessed using regression models, adjusting for relevant confounding factors including maternal pre-pregnancy BMI. Effect modification by infant sex was tested. RESULTS: One in four infants (24.6%) were born by CS delivery; 13.0% involved labor events and 11.6% did not. Infants born by CS without labor had an increased odds of being overweight at age 1 year compared to vaginally delivered infants after adjustment for maternal pre-pregnancy BMI, maternal diabetes, smoking, infant sex and birthweight-for-gestational age (aOR 1.68 [95% CI 1.05-2.67]). These effects did not persist to 3 or 5 years of age and, after stratification by sex, were only seen in boys (aOR at 1 year 2.21 [95% CI 1.26-3.88]). CONCLUSION AND RELEVANCE: Our findings add to the body of evidence that CS, in particular CS without labor events, may be a risk factor for overweight in early life, and that this association may be sex-specific. These findings could help to identify children at higher risk for developing obesity.

Maternal Iron and Vitamin D Status during the Second Trimester Is Associated with Third Trimester Depression Symptoms among Pregnant Participants in the APrON Cohort.

BACKGROUND: The maternal status of multiple micronutrients during pregnancy and postpartum and their potential associations with maternal health outcomes are largely undescribed. OBJECTIVES: This study aimed to examine associations between maternal iron and vitamin D status, individually and in combination, on depression symptoms in pregnant individuals. METHODS: The Alberta Pregnancy Outcomes and Nutrition cohort study included pregnant participants and their children from Calgary and Edmonton, Canada. Iron biomarkers (serum ferritin [SF], soluble transferrin receptor, and hepcidin) were measured via immunoassays and vitamin D [25-hydroxyvitamin D3 (25(OH)D3) and 3-epi-25-hydoxyvitamin D3 (3-epi-25(OH)D3)] metabolites were quantifed using liquid chromatography with tandem mass spectroscopy. Four categories of maternal iron and vitamin D status during the second trimester were conceptualized using concentrations of SF and total 25-hydoxyvitamin D [25(OH)D], respectively. Maternal Edinburgh Postnatal Depression Scale (EPDS) scores during the third trimester (n = 1920) and 3 mo postpartum (n = 1822) were obtained. RESULTS: Concentrations of maternal 25(OH)D3, 3-epi-25(OH)D3, and the ratio of both metabolites were significantly higher during the second trimester compared with their status at 3 mo postpartum. Higher second trimester maternal concentrations of SF (ß: -0.8; 95% confidence interval [CI]: -1.5, -0.01), hepcidin (ß: -0.5; 95% CI: -0.9, -0.2), and 25(OH)D3 (ß: -0.01; 95% CI: -0.02, -0.004) predicted lower maternal EPDS scores during the third trimester. Pregnant individuals with a low iron (SF <15 µg/L) and replete vitamin D (25(OH)D ≥75 nmol/L) (ß: 1.1; 95% CI: 0.03, 2.1) or low iron (SF <15 µg/L) and vitamin D (25(OH)D <75 nmol/L) (ß: 2.2; 95% CI: 0.3, 4.2) status during midpregnancy had higher third trimester EPDS scores compared with those that were replete in both micronutrients. CONCLUSIONS: A higher midpregnancy maternal iron and vitamin D status, independently or in combination, predicted fewer maternal depression symptoms in the third trimester. Concentrations of maternal 25(OH)D3 and 3-epi-25(OH)D3 may be lower in the postpartum period compared with midpregnancy.

Perinatal and early life factors and asthma control among preschoolers: a population-based retrospective cohort study.

BACKGROUND: Preventing poor childhood asthma control is crucial for short-term and long-term respiratory health. This study evaluated associations between perinatal and early-life factors and early childhood asthma control. METHODS: This retrospective study used administrative health data from mothers and children born 2010-2012 with a diagnosis of asthma before age 5 years, in Alberta, Canada. The outcome was asthma control within 2 years after diagnosis. Associations between perinatal and early-life factors and risk of partly and uncontrolled asthma were evaluated by multinomial logistic regression. RESULTS: Of 7206 preschoolers with asthma, 52% had controlled, 37% partly controlled and 12% uncontrolled asthma 2 years after diagnosis. Compared with controlled asthma, prenatal antibiotics (adjusted risk ratio (aRR): 1.19; 95% CI 1.06 to 1.33) and smoking (aRR: 1.18; 95% CI 1.02 to 1.37), C-section delivery (aRR: 1.11; 95% CI 1.00 to 1.25), summer birth (aRR: 1.16; 95% CI 1.00 to 1.34) and early-life hospitalisation for respiratory illness (aRR: 2.24; 95% CI 1.81 to 2.76) increased the risk of partly controlled asthma. Gestational diabetes (aRR: 1.41; 95% CI 1.06 to 1.87), C-section delivery (aRR: 1.18; 95% CI 1.00 to 1.39), antibiotics (aRR: 1.32; 95% CI 1.08 to 1.61) and hospitalisation for early-life respiratory illness (aRR: 1.65; 95% CI 1.19 to 2.27) were associated with uncontrolled asthma. CONCLUSION: Maternal perinatal and early-life factors including antibiotics in pregnancy and childhood, gestational diabetes, prenatal smoking, C-section and summertime birth, and hospitalisations for respiratory illness are associated with partly or uncontrolled childhood asthma. These results underline the significance of perinatal health and the lasting effects of early-life experiences on lung development and disease programming.

Maternal Iron Status Is Dynamic Throughout Pregnancy and Might Predict Birth Outcomes in a Sex Dependent Manner: Results from the Alberta Pregnancy Outcomes and Nutrition (APrON) Cohort Study.

BACKGROUND: Developmental responses to nutrient deprivation may differ by fetal sex. Despite this, relationships between maternal prenatal iron biomarkers and birth outcomes when stratifying by offspring sex are poorly described, especially in healthy cohorts. OBJECTIVES: This study aimed to determine associations between maternal iron biomarkers and birth weights (BWs) and birth head circumferences (BHCs) among female and male newborns to assess whether the potential predictive ability of iron biomarkers on birth outcomes differs by offspring sex. METHODS: The Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study recruited 2189 pregnant individuals from Calgary and Edmonton, Canada. Maternal blood was drawn at each trimester and 3 mo postpartum. Maternal serum ferritin (SF) concentrations were measured using chemiluminescent immunoassays and erythropoietin (EPO), hepcidin, and soluble transferrin receptor (sTfR) using enzyme-linked immunosorbent assays. Ratios of sTfR:SF and hepcidin:EPO were calculated and birth outcomes accessed through delivery records. Directed acyclic graphs informed multivariate regression models. RESULTS: The risk of maternal iron deficiency increased throughout pregnancy because ∼61% showed depleted iron stores (SF < 15 µg/L) by the third trimester. Maternal hepcidin, SF, sTfR, and sTfR:SF concentrations changed across time (P < 0.01), and participants carrying female fetuses consistently (across 6 biomarkers) showed a lower iron status during the third trimester compared with those with male fetuses (P < 0.05). Higher maternal SF and hepcidin:EPO during the third trimester was associated with lower BWs in males (P = 0.006 for SF; P = 0.03 for hepcidin:EPO) and females (P = 0.02 for SF; P = 0.02 for hepcidin:EPO). There were additional inverse associations between BWs and third trimester maternal hepcidin (P = 0.03) and hemoglobin (P = 0.004) and between BHCs and maternal SF (second trimester; P < 0.05) and Hb (third trimester P = 0.02) but only in males. CONCLUSIONS: Relationships between maternal iron biomarkers and BWs and BHCs may depend on the timing of pregnancy and offpsring sex. There was a high risk of third trimester iron storage depletion among generally healthy pregnant individuals.

Impact of maternal smoking on the infant gut microbiota and its association with child overweight: a scoping review.

BACKGROUND: Childhood obesity is a growing public health concern with evidence demonstrating that while infant exposure to maternal smoking is linked to low birth weight at birth, there is a rapid catch up in weight and increased risk of obesity in later life. This scoping review aims to synthesize up-to-date evidence on the impact of maternal smoking on the infant gut microbiota and its association with child overweight. METHODS: We conducted a PRISMA-compliant scoping review. Primary population-based cohort studies published between 1900 and April 2018 were included. Relevant publications were retrieved from seven databases: PubMed, Medline, Embase, Scopus, Biosis, Cochrane library, and Web of Science Core Collection. RESULTS: A total of three prospective cohort studies were included which utilized high-throughput 16S rRNA gene sequencing to assess the gut microbiota and included a total of 1277 infant/neonatal participants. Neonates exposed to environmental smoke had a higher relative abundance of Ruminococcus and Akkermansia. Infants exposed to environmental smoke during pregnancy or postnatally were found to have increased gut bacterial richness, particularly Firmicutes at 3 months of age, while 6-month-old infants born to smoking mothers had an increased abundance of Bacteroides and Staphylococcus. Elevated Firmicutes richness at 3 months of age was associated with elevated odds of child overweight and obesity at 1 and 3 years of age. CONCLUSION: The limited evidence to date warrants further large scale, longitudinal studies to explore the impact of maternal smoking and environmental tobacco smoke on the infant gut microbiome and its relation to child overweight.

Maternal Metabolic Complications in Pregnancy and Offspring Behavior Problems at 2 Years of Age.

Objectives Prenatal maternal metabolic problems such as pre-pregnancy adiposity, excess gestational weight gain, and gestational diabetes mellitus (GDM) are associated with an increased risk of psychopathology in offspring. We examined whether these exposures were linked to symptoms of emotional and behavioral problems in offspring at 2 years of age, or if associations were due to confounding variables. Methods Data from 815 mother-child pairs enrolled at the Edmonton site of the Canadian Healthy Infant Longitudinal Development cohort were used to examine associations between gestational metabolic complications and scores on the externalizing and internalizing scales of the Child Behavior Checklist (CBCL-1½ to 5) at age two. Associations between maternal metabolic complications and offspring psychopathology were assessed before and after adjustment for gestational diet, socioeconomic status (SES), postpartum depression (PPD), prenatal smoking and breastfeeding. Results Pre-pregnancy body mass index and GDM, but not gestational weight gain, predicted more offspring externalizing and internalizing problems. However, after adjustment for confounding variables, these associations were no longer statistically significant. Post-hoc analyses revealed that gestational diet accounted for unique variance in both externalizing (semi-partial rdiet = - 0.20, p < 0.001) and internalizing (semi-partial rdiet = - 0.16, p = 0.01) problems. PPD and SES also accounted for a similar amount of variance for both externalizing (semi-partial rPPD = 0.17, p < 0.001; rses = - 0.11, p = 0.03) and internalizing problems (semi-partial rPPD = 0.21, p < 0.001; rses = - 0.14, p = 0.004). Conclusions for Practice Since the confounding effect of gestational diet persisted after adjustment for, and was similar in magnitude to, SES and PPD, future research should consider the impact of unhealthy prenatal diets on offspring neurodevelopment.

Atopic dermatitis: Interaction between genetic variants of GSTP1, TNF, TLR2, and TLR4 and air pollution in early life.

BACKGROUND: Associations between traffic-related air pollution (TRAP) and childhood atopic dermatitis (AD) remain inconsistent, possibly due to unexplored gene-environment interactions. The aim of this study was to examine whether a potential effect of TRAP on AD prevalence in children is modified by selected single nucleotide polymorphisms (SNPs) related to oxidative stress and inflammation. METHODS: Doctor-diagnosed AD up to age 2 years and at 7-8 years, as well as AD symptoms up to age 2 years, was assessed using parental-reported questionnaires in six birth cohorts (N = 5685). Associations of nitrogen dioxide (NO2 ) estimated at the home address of each child at birth and nine SNPs within the GSTP1, TNF, TLR2, or TLR4 genes with AD were examined. Weighted genetic risk scores (GRS) were calculated from the above SNPs and used to estimate combined marginal genetic effects of oxidative stress and inflammation on AD and its interaction with TRAP. RESULTS: GRS was associated with childhood AD and modified the association between NO2 and doctor-diagnosed AD up to the age of 2 years (P(interaction) = .029). This interaction was mainly driven by a higher susceptibility to air pollution in TNF rs1800629 minor allele (A) carriers. TRAP was not associated with the prevalence of AD in the general population. CONCLUSIONS: The marginal genetic association of a weighted GRS from GSTP1, TNF, TLR2, and TLR4SNPs and its interaction with air pollution supports the role of oxidative stress and inflammation in AD.

Sex-Specific Differences in the Association Between Childhood Adversity and Cardiovascular Disease in Adulthood: Evidence From a National Cohort Study.

BACKGROUND: Childhood adversity increases the risk for cardiovascular disease (CVD) in adulthood. Previously proposed mechanisms suggest that the association is mediated by stress reactivity-known to be higher in women-and is aggravated by adult stress, but this has not yet been confirmed. Therefore, we investigated sex differences to better understand possible pathways from childhood adversity to CVD. METHODS: The National Population Health Survey, a 15-year cohort study of Canadians aged 18-49 years at baseline was used. Logistic regression with interaction terms for sex and stressful life events was used to assess the risk of CVD after childhood adversity. In secondary analyses, we assessed mediation effects of depression, smoking, alcohol, exercise, and diet using the product of coefficient approach. Mediated moderation was subsequently used to explain sex-moderated effects. RESULTS: There was a strong association between childhood adversity and CVD (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.56-2.94) for 3+ childhood adversities. The association was stronger with increasing stressful events, and female patients with 3+ stressful events exhibited the highest risk of CVD (OR, 4.40; 95% CI, 1.98-9.75). No association was found in men. Depression, smoking, and poor diet partially mediated the relationship between childhood adversity and CVD (14%, 9%, and 9%, respectively), but differences in these behaviours did not fully explain the sex-specific differences in the mediated moderation analysis. CONCLUSIONS: The effect of childhood adverse events on CVD is heightened among women, particularly women with stressful adulthoods, and this difference is not mediated by depression, smoking, or poor diet. These findings have important implications for understanding sex differences in CVD risk.

Genome-Wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up.

RATIONALE: The evidence supporting an association between traffic-related air pollution exposure and incident childhood asthma is inconsistent and may depend on genetic factors. OBJECTIVES: To identify gene-environment interaction effects on childhood asthma using genome-wide single-nucleotide polymorphism (SNP) data and air pollution exposure. Identified loci were further analyzed at epigenetic and transcriptomic levels. METHODS: We used land use regression models to estimate individual air pollution exposure (represented by outdoor NO2 levels) at the birth address and performed a genome-wide interaction study for doctors' diagnoses of asthma up to 8 years in three European birth cohorts (n = 1,534) with look-up for interaction in two separate North American cohorts, CHS (Children's Health Study) and CAPPS/SAGE (Canadian Asthma Primary Prevention Study/Study of Asthma, Genetics and Environment) (n = 1,602 and 186 subjects, respectively). We assessed expression quantitative trait locus effects in human lung specimens and blood, as well as associations among air pollution exposure, methylation, and transcriptomic patterns. MEASUREMENTS AND MAIN RESULTS: In the European cohorts, 186 SNPs had an interaction P < 1 × 10-4 and a look-up evaluation of these disclosed 8 SNPs in 4 loci, with an interaction P < 0.05 in the large CHS study, but not in CAPPS/SAGE. Three SNPs within adenylate cyclase 2 (ADCY2) showed the same direction of the interaction effect and were found to influence ADCY2 gene expression in peripheral blood (P = 4.50 × 10-4). One other SNP with P < 0.05 for interaction in CHS, rs686237, strongly influenced UDP-Gal:betaGlcNAc ß-1,4-galactosyltransferase, polypeptide 5 (B4GALT5) expression in lung tissue (P = 1.18 × 10-17). Air pollution exposure was associated with differential discs, large homolog 2 (DLG2) methylation and expression. CONCLUSIONS: Our results indicated that gene-environment interactions are important for asthma development and provided supportive evidence for interaction with air pollution for ADCY2, B4GALT5, and DLG2.

Postpartum depression, a direct and mediating risk factor for preschool wheeze in girls.

BACKGROUND: Postpartum depression affects over 1 in 10 child-bearing women. A growing body of evidence links maternal distress during the key developmental stages of infants with poor health outcomes, including wheeze and asthma. OBJECTIVE: We sought to investigate whether postpartum depression had an independent association with the development of wheeze in preschool-aged children. A second a priori objective was to ascertain whether postpartum depression functioned as a mediating factor for associations between wheeze, and prenatal distress and nutrition. METHODS: Data from the Community Perinatal Care Trial on maternal postpartum depression (Edinburgh Postnatal Depression Scale), the dependent variable, wheeze at age 3, and possible confounding factors were obtained for 791 women and their children in Calgary, Canada. Adjusted gender-specific logistic regression analyses were performed to test the association between postpartum depression and child wheeze, which was independent of maternal distress and vitamin use during pregnancy, pre/postnatal smoking, preterm birth, exclusive breastfeeding duration, daycare attendance, and maternal education. The potential mediating effects of postpartum depression were investigated in a path analysis. RESULTS: Wheeze at age 3 was almost 5 times more likely in girls of mothers who experienced postpartum depression. Results from a path analysis suggested that postpartum depression has a direct effect on wheeze (beta-coefficient=0.135, P < 0.05), and also mediates the effects of prenatal distress and vitamin use on wheeze in preschool girls. In boys, only prenatal smoking was a statistically significant predictor of wheeze, mainly through the effects of postnatal smoking. CONCLUSIONS & CLINICAL RELEVANCE: Postpartum depression may be a risk factor for preschool wheeze among girls in a low risk population, directly and indirectly through prenatal distress and vitamin use. Interventions which target postpartum depression and promote a healthy pregnancy may also reduce the risk of wheeze in children.

Maternal depressive symptoms across early childhood and asthma in school children: findings from a Longitudinal Australian Population Based Study.

There is a growing body of evidence attesting to links between early life exposure to stress and childhood asthma. However, available evidence is largely based on small, genetically high risk samples. The aim of this study was to explore the associations between the course of maternal depressive symptoms across early childhood and childhood asthma in a nationally representative longitudinal cohort study of Australian children. Participants were 4164 children and their biological mothers from the Longitudinal Study of Australian Children. Latent class analysis identified three trajectories of maternal depressive symptoms across four biennial waves from the first postnatal year to when children were 6-7 years: minimal symptoms (74.6%), sub-clinical symptoms (20.8%), and persistent and increasing high symptoms (4.6%). Logistic regression analyses revealed that childhood asthma at age 6-7 years was associated with persistent and increasing high depressive symptoms after accounting for known risk factors including smoking during pregnancy and maternal history of asthma (adjusted OR 2.36, 95% CI 1.61-3.45), p.001). Our findings from a nationally representative sample of Australian children provide empirical support for a relationship between maternal depressive symptoms across the early childhood period and childhood asthma. The burden of disease from childhood asthma may be reduced by strengthening efforts to promote maternal mental health in the early years of parenting.

GSTP1 and TNF Gene variants and associations between air pollution and incident childhood asthma: the traffic, asthma and genetics (TAG) study.

BACKGROUND: Genetics may partially explain observed heterogeneity in associations between traffic-related air pollution and incident asthma. OBJECTIVE: Our aim was to investigate the impact of gene variants associated with oxidative stress and inflammation on associations between air pollution and incident childhood asthma. METHODS: Traffic-related air pollution, asthma, wheeze, gene variant, and potential confounder data were pooled across six birth cohorts. Parents reported physician-diagnosed asthma and wheeze from birth to 7-8 years of age (confirmed by pediatric allergist in two cohorts). Individual estimates of annual average air pollution [nitrogen dioxide (NO2), particulate matter ≤ 2.5 µm (PM2.5), PM2.5 absorbance, ozone] were assigned to each child's birth address using land use regression, atmospheric modeling, and ambient monitoring data. Effect modification by variants in GSTP1 (rs1138272/Ala114Val and rs1695/IIe105Val) and TNF (rs1800629/G-308A) was investigated. RESULTS: Data on asthma, wheeze, potential confounders, at least one SNP of interest, and NO2 were available for 5,115 children. GSTP1 rs1138272 and TNF rs1800629 SNPs were associated with asthma and wheeze, respectively. In relation to air pollution exposure, children with one or more GSTP1 rs1138272 minor allele were at increased risk of current asthma [odds ratio (OR) = 2.59; 95% CI: 1.43, 4.68 per 10 µg/m3 NO2] and ever asthma (OR = 1.64; 95% CI: 1.06, 2.53) compared with homozygous major allele carriers (OR = 0.95; 95% CI: 0.68, 1.32 for current and OR = 1.20; 95% CI: 0.98, 1.48 for ever asthma; Bonferroni-corrected interaction p = 0.04 and 0.01, respectively). Similarly, for GSTP1 rs1695, associations between NO2 and current and ever asthma had ORs of 1.43 (95% CI: 1.03, 1.98) and 1.36 (95% CI: 1.08, 1.70), respectively, for minor allele carriers compared with ORs of 0.82 (95% CI: 0.52, 1.32) and 1.12 (95% CI: 0.84, 1.49) for homozygous major allele carriers (Bonferroni-corrected interaction p-values 0.48 and 0.09). There were no clear differences by TNF genotype. CONCLUSIONS: Children carrying GSTP1 rs1138272 or rs1695 minor alleles may constitute a susceptible population at increased risk of asthma associated with air pollution.

Traffic, asthma and genetics: combining international birth cohort data to examine genetics as a mediator of traffic-related air pollution's impact on childhood asthma.

Associations between traffic-related air pollution and incident childhood asthma can be strengthened by analysis of gene-environment interactions, but studies have typically been limited by lack of study power. We combined data from six birth cohorts on: asthma, eczema and allergic rhinitis to 7/8 years, and candidate genes. Individual-level assessment of traffic-related air pollution exposure was estimated using land use regression or dispersion modeling. A total of 11,760 children were included in the Traffic, Asthma and Genetics (TAG) Study; 6.3 % reported physician-diagnosed asthma at school-age, 16.0 % had asthma at anytime during childhood, 14.1 % had allergic rhinitis at school-age, 10.0 % had eczema at school-age and 33.1 % were sensitized to any allergen. For GSTP1 rs1138272, the prevalence of heterozygosity was 16 % (range amongst individual cohorts, 11-17 %) and homozygosity for the minor allele was 1 % (0-2 %). For GSTP1 rs1695, the prevalence of heterozygosity was 45 % (40-48 %) and homozygosity for the minor allele, 12 % (10-12 %). For TNF rs1800629, the prevalence of heterozygosity was 29 % (25-32 %) and homozygosity for the minor allele, 3 % (1-3 %). TAG comprises a rich database, the largest of its kind, for investigating the effect of genotype on the association between air pollution and childhood allergic disease.

Childhood allergic rhinitis, traffic-related air pollution, and variability in the GSTP1, TNF, TLR2, and TLR4 genes: results from the TAG Study.

BACKGROUND: Associations between traffic-related air pollution (TRAP) and allergic rhinitis remain inconsistent, possibly because of unexplored gene-environment interactions. OBJECTIVE: In a pooled analysis of 6 birth cohorts (Ntotal = 15,299), we examined whether TRAP and genetic polymorphisms related to inflammation and oxidative stress predict allergic rhinitis and sensitization. METHODS: Allergic rhinitis was defined with a doctor diagnosis or reported symptoms at age 7 or 8 years. Associations between nitrogen dioxide, particulate matter 2.5 (PM2.5) mass, PM2.5 absorbance, and ozone, estimated for each child at the year of birth, and single nucleotide polymorphisms within the GSTP1, TNF, TLR2, or TLR4 genes with allergic rhinitis and aeroallergen sensitization were examined with logistic regression. Models were stratified by genotype and interaction terms tested for gene-environment associations. RESULTS: Point estimates for associations between nitrogen dioxide, PM2.5 mass, and PM2.5 absorbance with allergic rhinitis were elevated, but only that for PM2.5 mass was statistically significant (1.37 [1.01, 1.86] per 5 µg/m(3)). This result was not robust to single-cohort exclusions. Carriers of at least 1 minor rs1800629 (TNF) or rs1927911 (TLR4) allele were consistently at an increased risk of developing allergic rhinitis (1.19 [1.00, 1.41] and 1.24 [1.01, 1.53], respectively), regardless of TRAP exposure. No evidence of gene-environment interactions was observed. CONCLUSION: The generally null effect of TRAP on allergic rhinitis and aeroallergen sensitization was not modified by the studied variants in the GSTP1, TNF, TLR2, or TLR4 genes. Children carrying a minor rs1800629 (TNF) or rs1927911 (TLR4) allele may be at a higher risk of allergic rhinitis.

Association of maternal diabetes and child asthma.

BACKGROUND: Perinatal programming is an emerging theory for the fetal origins of chronic disease. Maternal asthma and environmental tobacco smoke (ETS) are two of the best-known triggers for the perinatal programming of asthma, while the potential role of maternal diabetes has not been widely studied. OBJECTIVE: To determine if maternal diabetes is associated with child asthma, and if so, whether it modifies the effects of ETS exposure and maternal asthma. METHODS: We studied 3,574 Canadian children, aged 7-8 years, enrolled in a population-based birth cohort. Standardized questionnaires were completed by the children's parents, and data were analyzed by multivariable logistic regression. RESULTS: Asthma was reported in 442 children (12.4%). Compared to those without asthma, asthmatic children were more likely to have mothers (P = 0.003), but not fathers (P = 0.89), with diabetes. Among children without maternal history of diabetes, the likelihood of child asthma was 1.4-fold higher in those exposed to ETS (adjusted odds ratio, 1.40; 95% confidence interval, 1.13-1.73), and 3.6-fold higher in those with maternal asthma (3.59; 2.71-4.76). Among children born to diabetic mothers, these risks were amplified to 5.7-fold (5.68; 1.18-27.37) and 11.3-fold (11.30; 2.26-56.38), respectively. In the absence of maternal asthma or ETS, maternal diabetes was not associated with child asthma (0.65, 0.16-2.56). CONCLUSION: Our findings suggest that maternal diabetes may contribute to the perinatal programming of child asthma by amplifying the detrimental effects of ETS exposure and maternal asthma.

Influence of socioeconomic status trajectories on innate immune responsiveness in children.

OBJECTIVES: Lower socioeconomic status (SES) is consistently associated with poor health, yet little is known about the biological mechanisms underlying this inequality. In children, we examined the impact of early-life SES trajectories on the intensity of global innate immune activation, recognizing that excessive activation can be a precursor to inflammation and chronic disease. METHODS: Stimulated interleukin-6 production, a measure of immune responsiveness, was analyzed ex vivo for 267 Canadian schoolchildren from a 1995 birth cohort in Manitoba, Canada. Childhood SES trajectories were determined from parent-reported housing data using a longitudinal latent-class modeling technique. Multivariate regression was conducted with adjustment for potential confounders. RESULTS: SES was inversely associated with innate immune responsiveness (p=0.003), with persistently low-SES children exhibiting responses more than twice as intense as their high-SES counterparts. Despite initially lower SES, responses from children experiencing increasing SES trajectories throughout childhood were indistinguishable from high-SES children. Low-SES effects were strongest among overweight children (p<0.01). Independent of SES trajectories, immune responsiveness was increased in First Nations children (p<0.05) and urban children with atopic asthma (p<0.01). CONCLUSIONS: These results implicate differential immune activation in the association between SES and clinical outcomes, and broadly imply that SES interventions during childhood could limit or reverse the damaging biological effects of exposure to poverty during the preschool years.

Children's perceptions of healthful eating and physical activity.

PURPOSE: Healthful lifestyle habits established in childhood may continue through adulthood. Such habits may also be effective in preventing or reversing overweight and obesity. However, little is known about children's perceptions of healthful eating and physical activity. Thus, we sought a better understanding of how children perceive healthful eating and physical activity. METHODS: A purposeful selection was made of Winnipeg, Manitoba, boys (n=23) and girls (n=22) aged 11 to 12 years. The children were interviewed using a semi-structured, in-depth interview guide. Data were analyzed using thematic coding. RESULTS: Although healthful eating was seen as necessary for health, high-fat, high-sugar foods were a source of pleasure and enjoyed during social times. Physical activity was a way of spending time with friends, either through active play or watching sports. Boys viewed screen time and homework as barriers to physical activity, while girls identified no common barriers. Children viewed physical activity as easier than healthful eating, describing the former as "play" and "fun." CONCLUSIONS: Knowing how children think about food choices will further our understanding of the disconnect between nutrition knowledge and dietary behaviours. Understanding conflicting pressures that influence children's healthful lifestyles may enhance communication about these topics among parents, educators, and children.

Socioeconomic factors and home allergen exposure in children with asthma.

INTRODUCTION: The objective of this study was to determine the association between sociodemographic factors and the elimination of allergen sources from homes of asthmatic children. METHOD: In a cross-sectional analysis of data from 845 asthmatic children, multiple linear regression investigated the association between socioeconomic factors and failure to reduce allergen sources (i.e., stuffed toys, pets, carpeting, curtains, and cushions); failure to use linen covers; and not laundering linens weekly in hot water. Logistic regression assessed the relationship between socioeconomic status and exposure to environmental tobacco smoke. RESULTS: Mother's employment status was significantly associated with the quality of the home environment (P = .0002). Homemakers demonstrated fewer poor practices (3.1) compared with full-time or part-time employed mothers (3.6). Children whose mothers reported no post-secondary education were more likely to have environmental tobacco smoke exposure compared with those who had a post-secondary CE education or higher (OR 2.4, 95% CI 1.7, 3.5). DISCUSSION: Children whose mothers worked at home and were better educated were at reduced risk for exposure to sources of indoor allergens.