Prenatal oxidative balance and risk of asthma and allergic disease in adolescence.

BACKGROUND: Fetal oxidative balance (achieved when protective prenatal factors counteract sources of oxidative stress) might be critical for preventing asthma and allergic disease. OBJECTIVE: We examined prenatal intakes of hypothesized protective nutrients (including antioxidants) in conjunction with potential sources of oxidative stress in models of adolescent asthma and allergic disease. METHODS: We used data from 996 mother-child pairs in Project Viva. Exposures of interest were maternal prepregnancy body mass index and prenatal nutrients (energy-adjusted intakes of vitamins D, C, and E; ß-carotene; folate; choline; and n-3 and n-6 polyunsaturated fatty acids [PUFAs]), air pollutant exposures (residence-specific third-trimester black carbon or particulate matter with a diameter of less than 2.5 µm [PM2.5]), acetaminophen, and smoking. Outcomes were offspring's current asthma, allergic rhinitis, and allergen sensitization at a median age of 12.9 years. We performed logistic regression. Continuous exposures were log-transformed and modeled as z scores. RESULTS: We observed protective associations for vitamin D (odds ratio [OR], 0.69 [95% CI, 0.53-0.89] for allergic rhinitis), the sum of the n-3 PUFAs eicosapentaenoic acid and docosahexaenoic acid (OR, 0.81 [95% CI, 0.66-0.99] for current asthma), and the n-3 PUFA α-linolenic acid (OR, 0.78 [95% CI, 0.64-0.95] for allergen sensitization and OR, 0.80 [95% CI 0.65-0.99] for current asthma). Black carbon and PM2.5 were associated with an approximately 30% increased risk for allergen sensitization. No multiplicative interactions were observed for protective nutrient intakes with sources of oxidative stress. CONCLUSIONS: We identified potential protective prenatal nutrients (vitamin D and n-3 PUFAs), as well as adverse prenatal pro-oxidant exposures that might alter the risk of asthma and allergic disease into adolescence.

Gut microbiota and overweight in 3-year old children.

BACKGROUND: The gut microbiota has been associated with overweight and obesity in adults, but the evidence in children is limited. Our aim was to study whether composition of the gut microbiota at the age of 3 years is associated with overweight/obesity in children cross-sectionally. METHODS: Children, who participated in a clinical trial of prenatal vitamin-D supplementation (VDAART), underwent standardized height and weight measurements, and collection of stool samples at 3 years of age. 16 S rRNA sequencing (V4 region) of the stool samples were performed with Illumina MiSeq. Associations between microbiota and overweight/obesity (body mass index z-scores >85th percentile) was analyzed using logistic regression. RESULTS: Out of 502 children, 146 (29%) were categorized as overweight/obese. Maternal pre-pregnancy BMI, birth weight and length, formula feeding during the first year, high frequency of fast food consumption, and time watching TV or computer screen at 3 years were the risk factors for overweight/obesity. Of the top 20 most abundant genera, high relative abundance of Parabacteroidetes (Bacteroidetes; Bacteroidales) (aOR(95% CI): 0.69 (0.53, 0.90, p = 0.007) per interquartile increase) and unassigned genus within Peptostreptococcae family were inversely associated with overweight/obesity, whereas high relative abundance of Dorea (Firmicutes;Clostridiales) (1.23 (1.05, 1.43, p = 0.009)) was positively associated. Associations were independent of each other. No associations were found between diversity indices and overweight/obesity. CONCLUSIONS: Our data suggest that some of the differences in gut composition of bacteria between obese and non-obese adults can already be observed in 3-year old children. Longitudinal studies will be needed to determine long-term effects.

Relation of Prenatal Air Pollutant and Nutritional Exposures with Biomarkers of Allergic Disease in Adolescence.

Prenatal exposures may be critical for immune system development, with consequences for allergic disease susceptibility. We examined associations of prenatal exposures (nutrient intakes and air pollutants) with allergic disease biomarkers in adolescence. We used data from 857 mother-child pairs in Project Viva, a Massachusetts-based pre-birth cohort. Outcomes of interest at follow-up (median age 12.9 years) were fractional exhaled nitric oxide (FeNO) and total serum IgE. We applied Bayesian Kernel Machine Regression analyses to estimate multivariate exposure-response functions, allowing for exposure interactions. Exposures were expressed as z-scores of log-transformed data and we report effects in % change in FeNO or IgE z-score per increase in exposure from the 25th to 75th percentile. FeNO levels were lower with higher intakes of prenatal vitamin D (-16.15%, 95% CI: -20.38 to -2.88%), folate from foods (-3.86%, 95% CI: -8.33 to 0.83%) and n-3 PUFAs (-9.21%, 95% CI -16.81 to -0.92%). Prenatal air pollutants were associated with higher FeNO and IgE, with the strongest associations detected for PM2.5 with IgE (25.6% increase, 95% CI 9.34% to 44.29%). We identified a potential synergistic interaction (p = 0.02) between vitamin E (food + supplements) and PM2.5; this exposure combination was associated with further increases in FeNO levels.

Factors influencing the infant gut microbiome at age 3-6 months: Findings from the ethnically diverse Vitamin D Antenatal Asthma Reduction Trial (VDAART).

BACKGROUND: The gut microbiome in infancy influences immune system maturation, and may have an important impact on allergic disease risk. OBJECTIVE: We sought to determine how prenatal and early life factors impact the gut microbiome in a relatively large, ethnically diverse study population of infants at age 3 to 6 months, who were enrolled in Vitamin D Antenatal Asthma Reduction Trial, a clinical trial of vitamin D supplementation in pregnancy to prevent asthma and allergies in offspring. METHODS: We performed 16S rRNA gene sequencing on 333 infants' stool samples. Microbial diversity was computed using the Shannon index. Factor analysis applied to the top 25 most abundant taxa revealed 4 underlying bacterial coabundance groups; the first dominated by Firmicutes (Lachnospiraceae/Clostridiales), the second by Proteobacteria (Klebsiella/Enterobacter), the third by Bacteriodetes, and the fourth by Veillonella. Scores for coabundance groups were used as outcomes in regression models, with prenatal/birth and demographic characteristics as independent predictors. Multivariate analysis, using all microbial community members, was also conducted. RESULTS: White race/ethnicity was associated with lower diversity but higher Bacteroidetes coabundance scores. C-section birth was associated with higher diversity, but decreased Bacteroidetes coabundance scores. Firmicutes scores were higher for infants born by C-section. Breast-fed infants had lower proportions of Clostridiales. Cord blood vitamin D was linked to increased Lachnobacterium, but decreased Lactococcus. CONCLUSIONS: The findings presented here suggest that race, mode of delivery, breast-feeding, and cord blood vitamin D levels are associated with infant gut microbiome composition, with possible long-term implications for immune system modulation and asthma/allergic disease incidence.

Prenatal, perinatal, and childhood vitamin D exposure and their association with childhood allergic rhinitis and allergic sensitization.

BACKGROUND: The role of early-life vitamin D in childhood allergy is controversial. OBJECTIVE: We sought to assess vitamin D exposure in early life by multiple modalities and ascertain its association with childhood allergic rhinitis and allergic sensitization. METHODS: One thousand two hundred forty-eight mother-child pairs from a US prebirth cohort unselected for any disease were studied. Vitamin D exposure was assessed by measures of maternal intake during the first and second trimesters of pregnancy and serum 25-hydroxyvitamin D (25[OH]D) levels in mothers during pregnancy, cord blood, and children at school age (median age, 7.7 years; interquartile range, 1.0 years). Tests for associations between vitamin D exposure with ever allergic rhinitis, serum total IgE level, and allergen sensitization at school age were conducted. RESULTS: The correlations between maternal intake of vitamin D during pregnancy and serum 25(OH)D levels in pregnant mothers, cord blood, and children at school age were weak to moderate (r = -0.03 to 0.53). Each 100 IU/d of food-based vitamin D intake during the first and second trimesters (equivalent to the amount of vitamin D in an 8-ounce serving of milk) was associated with 21% and 20% reduced odds of ever allergic rhinitis at school age (odds ratios of 0.79 [95% CI, 0.67-0.92] and 0.80 [95% CI, 0.68-0.93]), respectively. There were no associations between maternal supplemental vitamin D intake or serum 25(OH)D levels at any time point with ever allergic rhinitis. There were no associations between any vitamin D exposure and serum total IgE level or allergen sensitization at school age. CONCLUSIONS: Inclusion of foods containing vitamin D in maternal diets during pregnancy may have beneficial effects on childhood allergic rhinitis.