Commercially used perfluorinated compounds (PFCs) have been widely detected in wildlife and humans, but the sources of human exposure are not fully characterized. The objectives of this study were to ...explore possible associations between concentrations of PFCs in serum and consumption of food with particular focus on seafood, and to compare estimated dietary intakes with determined serum PFC concentrations. Concentrations of 19 PFCs were determined in serum from 175 participants in the Norwegian Fish and Game Study and evaluated with respect to food consumption using multiple linear regression analysis. Associations between estimated individual total dietary intakes of PFCs and serum concentrations were also explored. PFC concentrations in serum were significantly associated (
p
<
0.05) with the consumption of lean fish, fish liver, shrimps and meat, as well as age, breastfeeding history and area of residence (R
2 0.35–0.63). The estimated dietary intakes of perfluorooctanoic acid (PFOA), perfluoroundecanoic acid (PFUnDA) and perfluorooctane sulfonic acid (PFOS) were 0.60, 0.34 and 1.5
ng/kg body weight/day, respectively. Seafood (fish and shellfish) was the major dietary source contributing 38% of the estimated dietary intakes of PFOA, 93% of PFUnDA and 81% of PFOS. The estimated dietary intakes of these three selected PFCs were significantly associated with the corresponding serum PFC concentrations (
p
<
0.05). In conclusion, our results show that consumption of fish and shellfish is a major determinant of serum PFC concentrations. Further, significant relationships between estimated dietary intakes and serum concentrations have been demonstrated for the first time.
Phthalates and bisphenol A (BPA) are ubiquitous in our environment. These chemicals have been characterized as endocrine disruptors that can cause functional impairment of development and ...reproduction. Processed and packaged foods are among the major sources of human exposure to these chemicals. No previous report showing the levels of these chemicals in food items purchased in Norway is available. The aim of the present study was to determine the concentration of ten different phthalates and BPA in foods and beverages purchased on the Norwegian market and estimate the daily dietary exposure in the Norwegian adult population. Commonly consumed foods and beverages in Norway were purchased in a grocery store and analysed using gas- and liquid chromatography coupled with mass spectrometry. Daily dietary exposures to these chemicals in the Norwegian adult population were estimated using the latest National dietary survey, Norkost 3 (2010–2011). This study showed that phthalates and BPA are found in all foods and beverages that are common to consume in Norway. The detection frequency of phthalates in the food items varied from 11% for dicyclohexyl phthalate (DCHP) to 84% for di-iso-nonyl phthalate (DiNP), one of the substitutes for bis(2-ethylhexyl) phthalate (DEHP). BPA was found in 54% of the food items analysed. Among the different phthalates, the highest concentrations were found for DEHP and DiNP in the food items. Estimated dietary exposures were also equally high and dominated by DEHP and DiNP (400–500ng/kg body weight (bw)/day), followed by di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), di-n-octyl phthalate (DnOP) and di-iso-decyl phthalate (DiDP) (30–40ng/kg bw/day). Dimethyl phthalate (DMP), diethylphthalate (DEP) and DCHP had the lowest concentrations and the exposures were around 10–20ng/kg bw/day. Estimated dietary exposure to BPA was 5ng/kg bw/day. In general, levels of phthalates and BPA in foods and beverages from the Norwegian market are comparable to other countries worldwide. Grain and meat products were the major contributors of exposure to these chemicals in the Norwegian adult population. The estimated dietary exposures to these chemicals were considerably lower than their respective tolerable daily intake (TDI) values established by the European Food Safety Authority (EFSA).
•Ten phthalates and bisphenol A were determined in food items bought in Norway.•Concentrations were highest for phthalates DEHP and DiNP.•Grain and meat products were major contributors to these chemicals in Norway.•Estimated dietary exposures were lower than respective tolerable daily intakes.
Pregnant women consume caffeine daily. The aim of this study was to examine the association between maternal caffeine intake from different sources and (a) gestational length, particularly the risk ...for spontaneous preterm delivery (PTD), and (b) birth weight (BW) and the baby being small for gestational age (SGA).
This study is based on the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health. A total of 59,123 women with uncomplicated pregnancies giving birth to a live singleton were identified. Caffeine intake from different sources was self-reported at gestational weeks 17, 22 and 30. Spontaneous PTD was defined as spontaneous onset of delivery between 22+0 and 36+6 weeks (n = 1,451). As there is no consensus, SGA was defined according to ultrasound-based (Marsal, n = 856), population-based (Skjaerven, n = 4,503) and customized (Gardosi, n = 4,733) growth curves.
The main caffeine source was coffee, but tea and chocolate were the main sources in women with low caffeine intake. Median pre-pregnancy caffeine intake was 126 mg/day (IQR 40 to 254), 44 mg/day (13 to 104) at gestational week 17 and 62 mg/day (21 to 130) at gestational week 30. Coffee caffeine, but not caffeine from other sources, was associated with prolonged gestation (8 h/100 mg/day, P <10-7). Neither total nor coffee caffeine was associated with spontaneous PTD risk. Caffeine intake from different sources, measured repeatedly during pregnancy, was associated with lower BW (Marsal-28 g, Skjaerven-25 g, Gardosi-21 g per 100 mg/day additional total caffeine for a baby with expected BW 3,600 g, P <10-25). Caffeine intake of 200 to 300 mg/day increased the odds for SGA (OR Marsal 1.62, Skjaerven 1.44, Gardosi 1.27, P <0.05), compared to 0 to 50 mg/day.
Coffee, but not caffeine, consumption was associated with marginally increased gestational length but not with spontaneous PTD risk. Caffeine intake was consistently associated with decreased BW and increased odds of SGA. The association was strengthened by concordant results for caffeine sources, time of survey and different SGA definitions. This might have clinical implications as even caffeine consumption below the recommended maximum (200 mg/day in the Nordic countries and USA, 300 mg/day according to the World Health Organization (WHO)) was associated with increased risk for SGA.
Characterization of the “exposome”, the set of all environmental factors that one is exposed to from conception onwards, has been advocated to better understand the role of environmental factors on ...chronic diseases.
Here, we aimed to describe the early-life exposome. Specifically, we focused on the correlations between multiple environmental exposures, their patterns and their variability across European regions and across time (pregnancy and childhood periods). We relied on the Human Early-Life Exposome (HELIX) project, in which 87 environmental exposures during pregnancy and 122 during the childhood period (grouped in 19 exposure groups) were assessed in 1301 pregnant mothers and their children at 6–11 years in 6 European birth cohorts.
Some correlations between exposures in the same exposure group reached high values above 0.8. The median correlation within exposure groups was >0.3 for many exposure groups, reaching 0.69 for water disinfection by products in pregnancy and 0.67 for the meteorological group in childhood. Median correlations between different exposure groups rarely reached 0.3. Some correlations were driven by cohort-level associations (e.g. air pollution and chemicals). Ten principal components explained 45% and 39% of the total variance in the pregnancy and childhood exposome, respectively, while 65 and 90 components were required to explain 95% of the exposome variability. Correlations between maternal (pregnancy) and childhood exposures were high (>0.6) for most exposures modeled at the residential address (e.g. air pollution), but were much lower and even close to zero for some chemical exposures.
In conclusion, the early life exposome was high dimensional, meaning that it cannot easily be measured by or reduced to fewer components. Correlations between exposures from different exposure groups were much lower than within exposure groups, which have important implications for co-exposure confounding in multiple exposure studies. Also, we observed the early life exposome to be variable over time and to vary by cohort, so measurements at one time point or one place will not capture its complexities.
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•The early-life exposome is high dimensional and not easily reducible to fewer components.•Correlations between exposures within the same exposure group can be high.•Correlations between exposures in different exposure groups are low.•The exposome varies strongly by location and by life period.
Background Whether probiotics, which can influence the microbiome, prevent infant eczema or allergic disease remains an open question. Most studies have focused on high-risk infants. Objectives We ...sought to assess whether consumption of probiotic milk products protects against atopic eczema, rhinoconjunctivitis, and asthma in early childhood in a large population-based pregnancy cohort (the Norwegian Mother and Child Cohort study). Methods We examined associations between consumption of probiotic milk products in pregnancy and infancy with questionnaire-reported atopic eczema, rhinoconjunctivitis, and asthma in 40,614 children. Relative risks (RRs) were calculated by using general linear models adjusted for potential confounders. Results Consumption of probiotic milk in pregnancy was associated with a slightly reduced relative risk (RR) of atopic eczema at 6 months (adjusted RR, 0.94; 95% CI, 0.89-0.99) and of rhinoconjunctivitis between 18 and 36 months (adjusted RR, 0.87; 95% CI, 0.78-0.98) compared with no consumption during pregnancy. Maternal history of allergic disease did not notably influence the associations. When both the mother (during pregnancy) and infant (after 6 months of age) had consumed probiotic milk, the adjusted RR of rhinoconjunctivitis was 0.80 (95% CI, 0.68-0.93) relative to no consumption by either. Probiotic milk consumption was not associated with asthma at 36 months. Conclusions In this population-based cohort consumption of probiotic milk products was related to a reduced incidence of atopic eczema and rhinoconjunctivitis, but no association was seen for incidence of asthma by 36 months of age.
Environment and diet in early life can affect development and health throughout the life course. Metabolic phenotyping of urine and serum represents a complementary systems-wide approach to elucidate ...environment-health interactions. However, large-scale metabolome studies in children combining analyses of these biological fluids are lacking. Here, we sought to characterise the major determinants of the child metabolome and to define metabolite associations with age, sex, BMI and dietary habits in European children, by exploiting a unique biobank established as part of the Human Early-Life Exposome project ( http://www.projecthelix.eu ).
Metabolic phenotypes of matched urine and serum samples from 1192 children (aged 6-11) recruited from birth cohorts in six European countries were measured using high-throughput
H nuclear magnetic resonance (NMR) spectroscopy and a targeted LC-MS/MS metabolomic assay (Biocrates AbsoluteIDQ p180 kit).
We identified both urinary and serum creatinine to be positively associated with age. Metabolic associations to BMI z-score included a novel association with urinary 4-deoxyerythreonic acid in addition to valine, serum carnitine, short-chain acylcarnitines (C3, C5), glutamate, BCAAs, lysophosphatidylcholines (lysoPC a C14:0, lysoPC a C16:1, lysoPC a C18:1, lysoPC a C18:2) and sphingolipids (SM C16:0, SM C16:1, SM C18:1). Dietary-metabolite associations included urinary creatine and serum phosphatidylcholines (4) with meat intake, serum phosphatidylcholines (12) with fish, urinary hippurate with vegetables, and urinary proline betaine and hippurate with fruit intake. Population-specific variance (age, sex, BMI, ethnicity, dietary and country of origin) was better captured in the serum than in the urine profile; these factors explained a median of 9.0% variance amongst serum metabolites versus a median of 5.1% amongst urinary metabolites. Metabolic pathway correlations were identified, and concentrations of corresponding metabolites were significantly correlated (r > 0.18) between urine and serum.
We have established a pan-European reference metabolome for urine and serum of healthy children and gathered critical resources not previously available for future investigations into the influence of the metabolome on child health. The six European cohort populations studied share common metabolic associations with age, sex, BMI z-score and main dietary habits. Furthermore, we have identified a novel metabolic association between threonine catabolism and BMI of children.
To examine the association between calculated maternal dietary exposure to Hg in pregnancy and infant birth weight in the Norwegian Mother and Child Cohort Study (MoBa).
Exposure was calculated with ...use of a constructed database of Hg in food items and reported dietary intake during pregnancy. Multivariable regression models were used to explore the association between maternal Hg exposure and infant birth weight, and to model associations with small-for-gestational-age offspring.
The study is based on data from MoBa.
The study sample consisted of 62 941 women who answered a validated FFQ which covered the habitual diet during the first five months of pregnancy.
Median exposure to Hg was 0·15 μg/kg body weight per week and the contribution from seafood intake was 88 % of total Hg exposure. Women in the highest quintile compared with the lowest quintile of Hg exposure delivered offspring with 34 g lower birth weight (95 % CI -46 g, -22 g) and had an increased risk of giving birth to small-for-gestational-age offspring, adjusted OR = 1·19 (95 % CI 1·08, 1·30). Although seafood intake was positively associated with increased birth weight, stratified analyses showed negative associations between Hg exposure and birth weight within strata of seafood intake.
Although seafood intake in pregnancy is positively associated with birth weight, Hg exposure is negatively associated with birth weight. Seafood consumption during pregnancy should not be avoided, but clarification is needed to identify at what level of Hg exposure this risk might exceed the benefits of seafood.
Pregnant women and their fetuses are exposed to multiple toxic metals that together with variations in essential element levels may alter epigenetic regulation, such as DNA methylation.
The aim of ...the study was to investigate the associations between gestational levels of toxic metals and essential elements and mixtures thereof, with global DNA methylation levels in pregnant women and their newborn children.
Using 631 mother-child pairs from a prospective birth cohort (The Norwegian Mother, Father and Child Cohort Study), we measured maternal blood concentration (gestation week ~18) of five toxic metals and seven essential elements. We investigated associations as individual exposures and two-way interactions, using elastic net regression, and total mixture, using quantile g-computation, with blood levels of 5-methylcytocine (5mC) and 5-hydroxymethylcytosine (5hmC) in mothers during pregnancy and their newborn children (cord blood). Multiple testing was adjusted for using the Benjamini and Hochberg false discovery rate (FDR) approach.
The most sensitive marker of DNA methylation appeared to be 5mC levels. In pregnant mothers, elastic net regression indicated associations between 5mC and selenium and lead (non-linear), while in newborns results indicated relationships between maternal selenium, cobalt (non-linear) and mercury and 5mC, as well as copper (non-linear) and 5hmC levels. Several possible two-way interactions were identified (e.g. arsenic and mercury, and selenium and maternal smoking in newborns). None of these findings met the FDR threshold for multiple testing. No net effect was observed in the joint (mixture) exposure-approach using quantile g-computation.
We identified few associations between gestational levels of several toxic metals and essential elements and global DNA methylation in pregnant mothers and their newborn children. As DNA methylation dysregulation might be a key mechanism in disease development and thus of high importance for public health, our results should be considered as important candidates to investigate in future studies.
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•One of the largest studies investigating associations between metals/essential elements and global DNA methylation in humans•12 metals/elements included, both individually, as mixtures, and as two-way interactions.•Mothers: possible association with DNA methylation for Se (positive) and Pb (non-linear)•Newborns: possible associations with DNA methylation for Se (positive), Hg (negative), and Co and Cu (non-linear)•Several possible two-way interactions for mothers and newborns, between exposures, and between exposures and covariates
Cerebral palsy (CP) is the most common motor disability in childhood, but its causes are only partly known. Early-life exposure to toxic metals and inadequate or excess amounts of essential elements ...can adversely affect brain and nervous system development. However, little is still known about these as perinatal risk factors for CP. This study aims to investigate the associations between second trimester maternal blood levels of toxic metals, essential elements, and mixtures thereof, with CP diagnoses in children.
In a large, population-based prospective birth cohort (The Norwegian Mother, Father, and Child Cohort Study), children with CP diagnoses were identified through The Norwegian Patient Registry and Cerebral Palsy Registry of Norway. One hundred forty-four children with CP and 1,082 controls were included. The relationship between maternal blood concentrations of five toxic metals and six essential elements and CP diagnoses were investigated using mixture approaches: elastic net with stability selection to identify important metals/elements in the mixture in relation to CP; then logistic regressions of the selected metals/elements to estimate odds ratio (OR) of CP and two-way interactions among metals/elements and with child sex and maternal education. Finally, the joint effects of the mixtures on CP diagnoses were estimated using quantile-based g-computation analyses.
The essential elements manganese and copper, as well as the toxic metal Hg, were the most important in relation to CP. Elevated maternal levels of copper (OR = 1.40) and manganese (OR = 1.20) were associated with increased risk of CP, while Hg levels were, counterintuitively, inversely related to CP. Metal/element interactions that were associated with CP were observed, and that sex and maternal education influenced the relationships between metals/elements and CP. In the joint mixture approach no significant association between the mixture of metals/elements and CP (OR = 1.00, 95% CI = 0.67, 1.50) was identified.
Using mixture approaches, elevated levels of copper and manganese measured in maternal blood during the second trimester could be related to increased risk of CP in children. The inverse associations between maternal Hg and CP could reflect Hg as a marker of maternal fish intake and thus nutrients beneficial for foetal brain development.
Telomere length is considered a biomarker of biological aging. Shorter telomeres and obesity have both been associated with age-related diseases. To evaluate the association between various indices ...of obesity with leukocyte telomere length (LTL) in childhood, data from 1,396 mother-child pairs of the multi-centre European birth cohort study HELIX were used. Maternal pre-pregnancy body mass index (BMI) and 4 adiposity markers in children at age 8 (6-11) years were assessed: BMI, fat mass, waist circumference, and skinfold thickness. Relative LTL was obtained. Associations of LTL with each adiposity marker were calculated using linear mixed models with a random cohort effect. For each 1 kg/m² increment in maternal pre-pregnancy BMI, the child's LTL was 0.23% shorter (95%CI: 0.01,0.46%). Each unit increase in child BMI z-score was associated with 1.21% (95%CI: 0.30,2.11%) shorter LTL. Inverse associations were observed between waist circumference and LTL (-0.96% per z-score unit; 95%CI: -2.06,0.16%), and skinfold thickness and LTL (-0.10% per z-score unit; 95%CI: -0.23,0.02%). In conclusion, this large multicentric study suggests that higher child adiposity indicators are associated with short telomeres in children, and that associations are stronger for child BMI than for maternal pre-pregnancy BMI.
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