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Background Individuals are exposed to environmental pollutants with endocrine disrupting activity (endocrine disruptors, EDCs) and the early stages of life are particularly susceptible to these exposures. Previous studies have foc...
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Background Individuals are exposed to environmental pollutants with endocrine disrupting activity (endocrine disruptors, EDCs) and the early stages of life are particularly susceptible to these exposures. Previous studies have focused on identifying molecular signatures associated with EDCs, but none have used repeated sampling strategy and integrated multiple omics. We aimed to identify multi-omic signatures associated with childhood exposure to non-persistent EDCs.Methods We used data from the HELIX Child Panel Study, which included 156 children aged 6 to 11. Children were followed for one week, in two time periods. Twenty-two non-persistent EDCs (10 phthalate, 7 phenol, and 5 organophosphate pesticide metabolites) were measured in two weekly pools of 15 urine samples each. Multi-omic profiles (methylome, serum and urinary metabolome, proteome) were measured in blood and in a pool urine samples. We developed visit-specific Gaussian Graphical Models based on pairwise partial correlations. The visit-specific networks were then merged to identify reproducible associations. Independent biological evidence was systematically sought to confirm some of these associations and assess their potential health implications.Results 950 reproducible associations were found among which 23 were direct associations between EDCs and omics. For 9 of them, we were able to find corroborating evidence from previous literature: DEP - serotonin, OXBE - cg27466129, OXBE - dimethylamine, triclosan - leptin, triclosan - serotonin, MBzP - Neu5AC, MEHP - cg20080548, oh-MiNP - kynurenine, oxo-MiNP ? 5-oxoproline. We used these associations to explore possible mechanisms between EDCs and health outcomes, and found links to health outcomes for 3 analytes: serotonin and kynurenine in relation to neuro-behavioural development, and leptin in relation to obesity and insulin resistance.Conclusions This multi-omics network analysis at two time points identified biologically relevant molecular signatures related to non-persistent EDC exposure in childhood, suggesting pathways related to neurological and metabolic outcomes.
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Early-life environmental exposures are suspected to be involved in the development of chronic diseases later in life. Most studies conducted so far considered single or few exposures and single-health parameter. Our study aimed to...
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Early-life environmental exposures are suspected to be involved in the development of chronic diseases later in life. Most studies conducted so far considered single or few exposures and single-health parameter. Our study aimed to identify a childhood general health score and assess its association with a wide range of pre- and post-natal environmental exposures.The analysis is based on 870 children (6–12 years) from six European birth cohorts participating in the Human Early-Life Exposome project. A total of 53 prenatal and 105 childhood environmental factors were considered, including lifestyle, social, urban and chemical exposures. We built a general health score by averaging three sub-scores (cardiometabolic, respiratory/allergy and mental) built from 15 health parameters. By construct, a child with a low score has a low general health status. Penalized multivariable regression through Least Absolute Shrinkage and Selection Operator (LASSO) was fitted in order to identify exposures associated with the general health score.The results of LASSO show that a lower general health score was associated with maternal passive and active smoking during pregnancy and postnatal exposure to methylparaben, copper, indoor air pollutants, high intake of caffeinated drinks and few contacts with friends and family. Higher child’s general health score was associated with prenatal exposure to a bluespace near residency and postnatal exposures to pets, cobalt, high intakes of vegetables and more physical activity. Against our hypotheses, postnatal exposure to organochlorine compounds and perfluorooctanoate were associated with a higher child’s general health score.By using a general health score summarizing the child cardiometabolic, respiratory/allergy and mental health, this study reinforced previously suspected environmental factors associated with various child health parameters (e.g. tobacco, air pollutants) and identified new factors (e.g. pets, bluespace) warranting further investigations.
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Background The influence of prenatal exposure to per- and poly- fluoroalkyl substances (PFAS) on birth size and offspring adiposity is unclear, especially for the newer, shorter-chained replacement PFAS. Methods In the GUSTO multi...
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Background The influence of prenatal exposure to per- and poly- fluoroalkyl substances (PFAS) on birth size and offspring adiposity is unclear, especially for the newer, shorter-chained replacement PFAS. Methods In the GUSTO multi-ethnic Singaporean mother-offspring cohort, 12 PFAS were measured in 783 cord plasma samples using ultra-performance-liquid chromatography-tandem-mass-spectrometer (UPLC-MS/MS). Outcomes included offspring anthropometry, other indicators of body composition/metabolic health, and MRI-derived abdominal adiposity (subset) at birth and 6?years of age. PFAS were modeled individually, in categories of long-chain and short-chain PFAS, and as scores of three principal components (PC) derived using PC analysis (PC1, PC2, and PC3 reflect predominant exposure patterns to “very-long-PFAS”, “long-PFAS”, and “short-PFAS”, respectively). Associations with outcomes were assessed using multivariable linear regressions, adjusted for important covariates such as maternal sociodemographic and lifestyle factors. Results Overall, cord PFAS levels showed either no or positive associations (mostly for long-chain PFAS) with birth weight, length and head circumference. In general, PFAS were associated with higher neonatal abdominal adiposity, driven by shorter-chain PFAS. Perfluoroheptanoic acid (PFHpA) was associated with higher volumes of superficial subcutaneous adipose tissue (sSAT) (3.75 [1.13, 6.37] mL per SD increase in PFAS) and internal adipose tissue (IAT) (1.39 [0.41, 2.38] mL). Higher levels of perfluorobutanesulfonic acid (PFBS), short-chain PFAS, and PC3 were associated with higher IAT volume (β range 1.22–1.41?mL/SD, all P?<?0.02), especially in girls. Higher PC3 score was additionally associated with higher sSAT (3.12 [0.45, 5.80] mL) volume. At age 6?years, most observed associations did not persist. No consistent associations were observed between PFAS and whole-body adiposity measures. Conclusions Fetal exposure to emerging short-chain PFAS was associated with higher abdominal adiposity at birth but not at age 6?years. Further research is needed to replicate the findings and to determine if these effects may reappear beyond early childhood. Population exposure to newer PFAS and consequent health impact must be monitored.
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Maternal glycaemia promotes fetal adiposity. Inositol, an insulin sensitizer, has been trialled for gestational diabetes prevention. The placenta has been implicated in how maternal hyperglycaemia generates fetal pathophysiology, ...
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Maternal glycaemia promotes fetal adiposity. Inositol, an insulin sensitizer, has been trialled for gestational diabetes prevention. The placenta has been implicated in how maternal hyperglycaemia generates fetal pathophysiology, but no studies have examined whether placental inositol biology is altered with maternal hyperglycaemia, nor whether such alterations impact fetal physiology. We aimed to investigate whether the effects of maternal glycaemia on offspring birthweight and adiposity at birth differed across placental inositol levels. Using longitudinal data from the Growing Up in Singapore Towards healthy Outcomes cohort, maternal fasting glucose (FPG) and 2-hour plasma glucose (2hPG) were obtained in pregnant women by a 75-g oral glucose tolerance test around 26 weeks' gestation. Relative placental inositol was quantified by liquid chromatography-mass spectrometry. Primary outcomes were birthweight (n-=-884) and abdominal adipose tissue (AAT) volumes measured by neonatal MRI scanning in a subset (n-=-262) of term singleton pregnancies. Multiple linear regression analyses were performed. Placental inositol was lower in those with higher 2hPG, no exposure to tobacco smoke antenatally, with vaginal delivery and shorter gestation. Positive associations of FPG with birthweight (adjusted [95% CI] 164.8-g [109.1, 220.5]) and AAT (17.3-ml [11.9, 22.6] per mmol glucose) were observed, with significant interactions between inositol tertiles and FPG in relation to these outcomes (p-<-0.05). Stratification by inositol tertiles showed that each mmol/L increase in FPG was associated with increased birthweight and AAT volume among cases within the lowest (birthweight-=-174.2-g [81.2, 267.2], AAT-=-21.0-ml [13.1, 28.8]) and middle inositol tertiles (birthweight-=-202.0-g [103.8, 300.1], AAT-=-19.7-ml [9.7, 29.7]). However, no significant association was found among cases within the highest tertile (birthweight-=-81.0-g [ 21.2, 183.2], AAT-=-0.8-ml [ 8.4, 10.0]). High placental inositol may protect the fetus from the pro-adipogenic effects of maternal glycaemia. Studies are warranted to investigate whether prenatal inositol supplementation can increase placental inositol and reduce fetal adiposity.
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Introduction Reducing protein intake is recommended for slowing chronic kidney disease (CKD) progression, but assessment of its true effectiveness is sparse. Methods Using the Maroni formula, we assessed dietary protein intake (DP...
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Introduction Reducing protein intake is recommended for slowing chronic kidney disease (CKD) progression, but assessment of its true effectiveness is sparse. Methods Using the Maroni formula, we assessed dietary protein intake (DPI) from 24-hour urinary urea excretion in 1594 patients (67% men and 33% women) with CKD, 784 of whom also had 7-day food records. Cause-specific hazard ratios (HRs) and 95% confidence intervals for the competing risks of DPI-associated end-stage renal disease (ESRD) or death were estimated in 1412 patients with baseline glomerular filtration rate?≥15 ml/min per 1.73 m 2 , measured by 51 Cr-EDTA renal clearance (mGFR). Results Overall, mean DPI estimated from urea excretion was 1.09 ± 0.30 g/kg of body weight per day (range?= 0.34?2.76); 20% of patients had values > 1.3 g/kg per day, and 1.9% had values?< 0.6 g/kg per day. Urea excretion and food records produced similar estimates of mean DPI. The lower the mGFR, the lower the mean DPI. Over a median follow-up of 5.6 years, there were 319 ESRD events and 189 pre-ESRD deaths. After adjusting for relevant covariates, each 0.1 g/kg daily higher baseline urea excretion?based DPI or food record?based DPI was associated with an HR for ESRD of 1.05 (95% confidence interval 1.01?1.10) or 1.09 (95% confidence interval 1.04?1.14), respectively. HRs were stronger in patients with baseline mGFR?< 30 ml/min per 1.73 m 2 . There was no association with mortality. The mean age of the patients was 59 ± 15 years, and mean body mass index was 26.6 ± 5.2 kg/m 2 . Conclusion In this prospective observational study, the lower the baseline DPI, the slower the progression toward ESRD. Most importantly, the absence of threshold for the relation between DPI and ESRD risk indicates that there is no optimal DPI in the range observed in this cohort.
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Identifying the determinants of child’s liking for different foods may help to prevent future choices of unhealthy food. To study early-life food-related characteristics associated with child’s liking for different foods at 5y w...
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Identifying the determinants of child’s liking for different foods may help to prevent future choices of unhealthy food. To study early-life food-related characteristics associated with child’s liking for different foods at 5y with a longitudinal study. 1142 5y- old children completed a liking test for “fruit and vegetables”, “meat, fish and eggs”, desserts and cheese. Data related to maternal food intake before pregnancy, infant feeding during the first year of life, maternal feeding practices at 2y, child’s food intake at 3y, and child’s food neophobia from 1 to 4y were collected prospectively from the mother. The associations between these factors and child‘s liking for each category of foods were analyzed using structural equation modelling. High food neophobia at 4 y was related to lower child’s liking for all food groups. Maternal feeding practices at 2y were associated with liking for dessert: negatively for the practices allowing child to control his/her own food intake, positively for restriction of child’s food intake for weight reasons. Moreover, child’s food intake at 3y was positively associated with child’s liking for “fruit and vegetables” as well as for cheese. Finally, adherence to the infant feeding pattern “long breastfeeding, later introduction of main meal components and use of home-made products” was positively associated with child’s liking for meat/fish/eggs. For all food groups, food neophobia was a common determinant of child’s liking for food at 5y, whereas other factors were associated with food liking for specific food groups.
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Identifying dietary factors associated with blood pressure in children and adolescents could help guide recommendations for prevention of elevated blood pressure. Our objective was to examine the association between blood pressure...
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Identifying dietary factors associated with blood pressure in children and adolescents could help guide recommendations for prevention of elevated blood pressure. Our objective was to examine the association between blood pressure and dairy product consumption during preadolescence in a cross-sectional study. Baseline data from 610 children aged 8 to 10 years from the Quebec Adipose and Lifestyle Investigation in Youth cohort was used for this analysis. Blood pressure was measured using a standard protocol. Children's average dairy intake was assessed from three nonconsecutive 24-hour dietary recalls, and was divided into tertiles. Linear regression models adjusted for age; sex; height; physical activity level; sugar-sweetened beverages, total energy, calcium, sodium, and saturated fat intake; parental history of hypertension; parental education; weight status; and intake of fruits and vegetables. In our fully adjusted model, high dairy intake (>=2 servings of dairy per day) was associated with 1.74 mm Hg lower systolic blood pressure (P<0.05) and with 0.87 mm Hg lower diastolic blood pressure (P=0.10) compared with low intake. We found no significant association of calcium, magnesium, or potassium intake on children's blood pressure, suggesting the role of other antihypertensive components in dairy products. Our results indicate that high intake of dairy (>=2 servings per day) has antihypertensive effects on blood pressure among youth
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