Excessive Unbalanced Meat Consumption in the First Year of Life Increases Asthma Risk in the PASTURE and LUKAS2 Birth Cohorts.

A higher diversity of food items introduced in the first year of life has been inversely related to subsequent development of asthma. In the current analysis, we applied latent class analysis (LCA) to systematically assess feeding patterns and to relate them to asthma risk at school age. PASTURE (N=1133) and LUKAS2 (N=228) are prospective birth cohort studies designed to evaluate protective and risk factors for atopic diseases, including dietary patterns. Feeding practices were reported by parents in monthly diaries between the 4th and 12th month of life. For 17 common food items parents indicated frequency of feeding during the last 4 weeks in 4 categories. The resulting 153 ordinal variables were entered in a LCA. The intestinal microbiome was assessed at the age of 12 months by 16S rRNA sequencing. Data on feeding practice with at least one reported time point was available in 1042 of the 1133 recruited children. Best LCA model fit was achieved by the 4-class solution. One class showed an elevated risk of asthma at age 6 as compared to the other classes (adjusted odds ratio (aOR): 8.47, 95% CI 2.52-28.56, p = 0.001) and was characterized by daily meat consumption and rare consumption of milk and yoghurt. A refined LCA restricted to meat, milk, and yoghurt confirmed the asthma risk effect of a particular class in PASTURE and independently in LUKAS2, which we thus termed unbalanced meat consumption (UMC). The effect of UMC was particularly strong for non-atopic asthma and asthma irrespectively of early bronchitis (aOR: 17.0, 95% CI 5.2-56.1, p < 0.001). UMC fostered growth of iron scavenging bacteria such as Acinetobacter (aOR: 1.28, 95% CI 1.00-1.63, p = 0.048), which was also related to asthma (aOR: 1.55, 95% CI 1.18-2.03, p = 0.001). When reconstructing bacterial metabolic pathways from 16S rRNA sequencing data, biosynthesis of siderophore group nonribosomal peptides emerged as top hit (aOR: 1.58, 95% CI 1.13-2.19, p = 0.007). By a data-driven approach we found a pattern of overly meat consumption at the expense of other protein sources to confer risk of asthma. Microbiome analysis of fecal samples pointed towards overgrowth of iron-dependent bacteria and bacterial iron metabolism as a potential explanation.

Caffeine content in newborn hair correlates with maternal dietary intake.

PURPOSE: High-maternal caffeine intake during pregnancy may be harmful for perinatal outcomes and future child health, but the level of fetal cumulative exposure has been difficult to measure thus far. Here, we present maternal dietary caffeine intake during the last trimester and its correlation to caffeine content in newborn hair after birth. METHODS: Maternal third trimester diets and dietary caffeine intake were prospectively collected in Kuopio Birth Cohort (KuBiCo) using a 160-item food frequency questionnaire (n = 2840). Newborn hair was collected within 48 h after birth and analyzed by high-resolution mass spectrometry (HRMS) for caffeine (n = 316). Correlation between dietary caffeine intake and neonatal hair caffeine content was evaluated from 203 mother-child pairs. RESULTS: Mean dietary caffeine intake was 167 mg/days (95% CI 162-172  mg/days), of which coffee comprised 81%. Caffeine in the maternal diet and caffeine content in newborn hair correlated significantly (r = 0.50; p < 0.001). Older, multiparous, overweight women, and smokers had the highest caffeine levels in the maternal diet, as well as in their newborn babies' hair. CONCLUSION: Caffeine exposure, estimated from newborn hair samples, reflects maternal third trimester dietary caffeine intake and introduces a new method to assess fetal cumulative caffeine exposure. Further studies to evaluate the effects of caffeine exposure on both perinatal and postnatal outcomes are warranted, since over 40% of pregnant women consume caffeine more than the current suggested recommendations (European Food Safety Association, EFSA recommendations).

Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis.

BACKGROUND: Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases, such as allergy, asthma, and inflammatory bowel disease. OBJECTIVE: We sought to investigate whether both exposure to microbes and exposure to structures of nonmicrobial origin, such as the sialic acid N-glycolylneuraminic acid (Neu5Gc), might play a significant role. METHODS: Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in sera of children enrolled in 2 farm studies: the Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 299) and the Protection Against Allergy Study in Rural Environments (PASTURE) birth cohort (cord blood [n = 836], 1 year [n = 734], 4.5 years [n = 700], and 6 years [n = 728]), and we associated them with asthma and wheeze. The effect of Neu5Gc was examined in murine airway inflammation and colitis models, and the role of Neu5Gc in regulating immune activation was assessed based on helper T-cell and regulatory T-cell activation in mice. RESULTS: In children anti-Neu5Gc IgG levels correlated positively with living on a farm and increased peripheral blood forkhead box protein 3 expression and correlated inversely with wheezing and asthma in nonatopic subjects. Exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Furthermore, Neu5Gc administration to mice reduced the severity of a colitis model. Mechanistically, we found that Neu5Gc exposure reduced IL-17+ T-cell numbers and supported differentiation of regulatory T cells. CONCLUSIONS: In addition to microbial exposure, increased exposure to non-microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment.

ω-3 fatty acids contribute to the asthma-protective effect of unprocessed cow's milk.

BACKGROUND: Living on a farm has repeatedly been shown to protect children from asthma and allergies. A major factor involved in this effect is consumption of unprocessed cow's milk obtained directly from a farm. However, this phenomenon has never been shown in a longitudinal design, and the responsible milk components are still unknown. OBJECTIVES: We sought to assess the asthma-protective effect of unprocessed cow's milk consumption in a birth cohort and to determine whether the differences in the fatty acid (FA) composition of unprocessed farm milk and industrially processed milk contributed to this effect. METHODS: The Protection Against Allergy-Study in Rural Environments (PASTURE) study followed 1133 children living in rural areas in 5 European countries from birth to age 6 years. In 934 children milk consumption was assessed by using yearly questionnaires, and samples of the "usually" consumed milk and serum samples of the children were collected at age 4 years. Doctor-diagnosed asthma was parent reported at age 6 years. In a nested case-control study of 35 asthmatic and 49 nonasthmatic children, 42 FAs were quantified in milk samples. RESULTS: The risk of asthma at 6 years of age was reduced by previous consumption of unprocessed farm milk compared with shop milk (adjusted odds ratio for consumption at 4 years, 0.26; 95% CI, 0.10-0.67). Part of the effect was explained by the higher fat content of farm milk, particularly the higher levels of ω-3 polyunsaturated FAs (adjusted odds ratio, 0.29; 95% CI, 0.11-0.81). CONCLUSION: Continuous farm milk consumption in childhood protects against asthma at school age partially by means of higher intake of ω-3 polyunsaturated FAs, which are precursors of anti-inflammatory mediators.

Well water radioactivity and risk of cancers of the urinary organs.

Water from bedrock frequently contains higher concentrations of natural radionuclides than water from other sources. Bladder and kidneys receive a radiation dose when radioactive isotopes are excreted into urine. The subjects for this case-cohort study were selected from all drilled wells users in Finland. The study comprised 61 bladder cancer and 51 kidney cancer cases diagnosed between 1981 and 1995, as well as a random sample of 274 reference persons, stratified by age and sex. The median activity concentrations of radon in drilled wells used by bladder and kidney cancer cases and the reference cohort were 170, 140, and 130 Bq/L, respectively. The radium concentration was 0.01 Bq/L for all groups and the uranium concentrations were 0.08, 0.07, and 0.06 Bq/L, respectively. The bladder cancer risks associated with radon, radium, and uranium activity concentrations in drinking water were 1.02 (0.68-1.54) per log(100 Bq of radon/L), 0.73 (0.21-2.50) per log(0.1 Bq of radium/L), and 0.77 (0.32-1.89) per log(1 Bq of uranium/L). The corresponding figures for kidney cancer were 0.81 (0.47-1.37), 0.12 (0.01-1.10), and 0.92 (0.36-2.35), respectively. In conclusion, even though ingested radionuclides from drilled wells are a source of radiation exposure, they are not associated with a substantially increased risk of bladder or kidney cancers in concentrations occurring in drilled wells.

Characterizing microbial exposure with ergosterol, 3-hydroxy fatty acids, and viable microbes in house dust: determinants and association with childhood asthma.

The authors assessed determinants of ergosterol, 3-OH fatty acids (FAs), and viable microbes in vacuum cleaner dust, and investigated the association between these microbial markers and childhood asthma. The authors studied the homes of 36 children who were new cases of childhood asthma and the homes of 36 controls. Home characteristics explained 34% to 44% of the variation in levels of different microbial groups. Determinants of 3-OH FAs were a lower level of cleanliness, having a fireplace, having livestock, and moisture damage; determinants of viable bacteria were the level of home repair needed and the material used in the building frame of the home. Ergosterol was associated with the presence of livestock and the practice of cleaning rugs outside; viable fungi was associated with the material used in the building frame, visible mold, and the practice of cleaning rugs outside. Exposure to mesophilic actinomycetes was nonsignificantly associated with risk of asthma. The authors concluded that the variation of microbial levels in dust could be explained relatively well by home characteristics, and suggested that exposure to mesophilic actinomycetes may increase the risk of new asthma.

Radon and other natural radionuclides in drinking water and risk of stomach cancer: a case-cohort study in Finland.

Very high concentrations of naturally occurring radionuclides are encountered in Finnish groundwaters and wells. Radon ingested through drinking water can cause considerable radiation to the stomach. We assessed the effect of natural uranium and other radionuclides in drinking water on the risk of stomach cancer. Subjects (n = 144,627) in the base cohort had lived outside the municipal tap water system during 1967-1980. A subcohort of 4,590 subjects was formed for use as a reference group by random sampling of the base cohort, with stratification by age and sex. Within the subcohort, 371 subjects had used drinking water from drilled wells prior to 1981. Stomach cancer cases within the subcohort were identified through a cancer registry, and cases using water from drilled wells were selected. Activity concentrations of radon, radium-226 and natural uranium in the drinking water were analyzed using radiochemical and alpha spectrometric methods. The median activity concentration of radon in well water was 130 Bq/l for both the 88 stomach cancer cases and the 274 subjects in the subcohort. Median radium concentrations were 0.007 Bq/l for cases and 0.010 Bq/l for the subcohort, with a median uranium concentration of 0.07 Bq/l for both groups. Risk of stomach cancer was not associated with exposure to radon or other radionuclides. The hazard ratio of stomach cancer was 0.68 for radon (95% CI 0.29-1.59 at 100 Bq/l water), 0.69 per Bq/1 for radium-226 (95% CI 0.33-1.47) and 0.76 per Bq/1 for uranium (95% CI 0.48-1.21). Our results do not indicate an increased risk of stomach cancer from ingestion of radon or other natural radionuclides through drinking water at these exposure levels.

Infant vitamin d supplementation and allergic conditions in adulthood: northern Finland birth cohort 1966.

Allergen-induced secretion of Th2-type cytokines and IgE production have recently been reported to be increased in mice treated with 1,25(OH)(2)D, the active form of vitamin D. Our objective was to investigate whether vitamin D supplementation in infancy is associated with the risk of atopy, allergic rhinitis, and asthma. The Northern Finland Birth Cohort consists of all individuals in the two most northern provinces of Finland who were due to be born in 1966. Data on vitamin D supplementation during the first year of life was obtained in 1967. Current asthma and allergic rhinitis were reported at age 31 years (n = 7,648), and atopy determined by skin-prick test in a sub-sample still living in northern Finland or the Helsinki area (n = 5,007). The prevalence of atopy and allergic rhinitis at age 31 years was higher in participants who had received vitamin D supplementation regularly during the first year compared to others (OR 1.46, 95%CI 1.4-2.0, and OR 1.66, 95%CI 1.1-1.6, respectively). A similar association was observed for asthma (OR 1.35, 95%CI 0.99-1.8). These associations persisted after adjustment for a wide range of behavioral and social factors (adjusted: OR 1.33 for all, P = 0.01 for atopy, P = 0.001 for allergic rhinitis, and P = 0.08 for asthma). We observed an association between vitamin D supplementation in infancy and an increased risk of atopy and allergic rhinitis later in life. Further study is required to determine whether these observations reflect long-term effects on immune regulation or differences in unmeasured determinants of vitamin D supplementation.

Uranium and other natural radionuclides in drinking water and risk of leukemia: a case-cohort study in Finland.

OBJECTIVE: We assessed the effect of natural uranium and other radionuclides in drinking water on risk of leukemia. METHODS: The subjects (n = 144,627) in the base cohort had lived outside the municipal tapwater system during 1967-1980. A subcohort was formed as a stratified random sample of the base cohort and subjects using drinking water from drilled wells prior to 1981 were identified. A case-cohort design was used comparing exposure among cases with leukemia (n = 35) with a stratified random sample (n = 274) from the subcohort. Activity concentrations of uranium, radium-226, and radon in the drinking water were analyzed using radiochemical and alpha-spectrometric methods. RESULTS: The median activity concentration of uranium in well water was 0.08 Bq/L for the leukemia cases and 0.06 Bq/L for the reference group, radon concentrations 80 and 130 Bq/L, respectively, and radium-226 concentrations 0.01 Bq/L for both groups. The hazard ratio of leukemia for uranium was 0.91 (95% confidence interval 0.73-1.13) per Bq/L. for radon 0.79 per Bq/L (95% CI 0.27-2.29), and for radium-226 0.80 (95% CI 0.46-1.39) per Bq/L. CONCLUSIONS: Our results do not indicate an increased risk of leukemia from ingestion of natural uranium or other radionuclides through drinking water at these exposure levels.

Renal effects of uranium in drinking water.

Animal studies and small studies in humans have shown that uranium is nephrotoxic. However, more information about its renal effects in humans following chronic exposure through drinking water is required. We measured uranium concentrations in drinking water and urine in 325 persons who had used drilled wells for drinking water. We measured urine and serum concentrations of calcium, phosphate, glucose, albumin, creatinine, and beta-2-microglobulin to evaluate possible renal effects. The median uranium concentration in drinking water was 28 microg/L (interquartile range 6-135, max. 1,920 microg/L) and in urine 13 ng/mmol creatinine (2-75), resulting in the median daily uranium intake of 39 microg (7-224). Uranium concentration in urine was statistically significantly associated with increased fractional excretion of calcium and phosphate. Increase of uranium in urine by 1 microg/mmol creatinine increased fractional excretion of calcium by 1.5% [95% confidence interval (CI), 0.6-2.3], phosphate by 13% (1.4-25), and glucose excretion by 0.7 micromol/min (-0.4-1.8). Uranium concentrations in drinking water and daily intake of uranium were statistically significantly associated with calcium fractional excretion, but not with phosphate or glucose excretion. Uranium exposure was not associated with creatinine clearance or urinary albumin, which reflect glomerular function. In conclusion, uranium exposure is weakly associated with altered proximal tubulus function without a clear threshold, which suggests that even low uranium concentrations in drinking water can cause nephrotoxic effects. Despite chronic intake of water with high uranium concentration, we observed no effect on glomerular function. The clinical and public health relevance of the findings are not easily established, but our results suggest that the safe concentration of uranium in drinking water may be within the range of the proposed guideline values of 2-30 microg/L.