•Increased dietary fiber intake was associated with decreased levels of three PFAS.•Analysis was carried out using data from 6482 NHANES participants.•Largest effect for PFNA with 8.36% decrease with ...an interquartile increase in fiber.•Smallest effect in PFOA with 3.64% decrease with an interquartile increase in fiber.•This association may confound the association between serum cholesterol and PFAS.
Fiber-rich food intake has been associated with lower serum concentrations of perfluoroalkyl substances (PFAS) in some studies and dietary fiber was related to lower serum PFAS in a recent study. Given the previous epidemiologic data suggesting that fiber might decrease serum PFAS concentrations, we examined the relation of serum PFAS concentrations to intake of dietary fiber in National Health and Nutrition Examination Survey (NHANES) data. We examined the PFAS-fiber association among 6482 adults who participated in the NHANES, 2005–2016. Fiber intake was estimated based on two 24-hour diet recalls. We adjusted the models for determinants of PFAS and potentially confounding factors such as intake of foods reported to increase PFAS exposure. Results were expressed as the percent difference in PFAS concentration per interquartile range (IQR) increase in fiber (and 95 percent confidence interval), and the NHANES sampling parameters were used to make the results generalizable to the U.S. The adjusted percent difference in perfluorooctanoic acid (PFOA) per IQR increase in fiber was −3.64 (−6.15, −1.07); for perfluorooctane sulfonic acid (PFOS) was −6.69 (−9.57, −3.73), and for perfluorononanoic acid (PFNA) was −8.36 (−11.33, −5.29). These results suggest that dietary fiber increases the gastrointestinal excretion of PFOA, PFOS, and PFNA. Because fiber also lowers serum cholesterol, in some studies of the serum cholesterol-PFAS relationship confounding by fiber may be worth evaluating.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Meta-analysis poses a challenge when original study results have been expressed in a non-uniform manner, such as when regression results from some original studies were based on a log-transformed key ...independent variable while in others no transformation was used. Methods of re-expressing regression coefficients to generate comparable results across studies regardless of data transformation have recently been developed. We examined the relative bias of three re-expression methods using simulations and 15 real data examples where the independent variable had a skewed distribution. Regression coefficients from models with log-transformed independent variables were re-expressed as though they were based on an untransformed variable. We compared the re-expressed coefficients to those from a model fit to the untransformed variable. In the simulated and real data, all three re-expression methods usually gave biased results, and the skewness of the independent variable predicted the amount of bias. How best to synthesize the results of the log-transformed and absolute exposure evidence streams remains an open question and may depend on the scientific discipline, scale of the outcome, and other considerations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Diabetes affects an estimated 346 million persons globally, and total deaths from diabetes are projected to increase > 50% in the next decade. Understanding the role of environmental ...chemicals in the development or progression of diabetes is an emerging issue in environmental health. In 2011, the National Toxicology Program (NTP) organized a workshop to assess the literature for evidence of associations between certain chemicals, including inorganic arsenic, and diabetes and/or obesity to help develop a focused research agenda. This review is derived from discussions at that workshop. Objectives: Our objectives were to assess the consistency, strength/weaknesses, and biological plausibility of findings in the scientific literature regarding arsenic and diabetes and to identify data gaps and areas for future evaluation or research. The extent of the existing literature was insufficient to consider obesity as an outcome. Data Sources, Extraction, and Synthesis: Studies related to arsenic and diabetes or obesity were identified through PubMed and supplemented with relevant studies identified by reviewing the reference lists in the primary literature or review articles. Conclusions: Existing human data provide limited to sufficient support for an association between arsenic and diabetes in populations with relatively high exposure levels (≥ 150 μg arsenic/L in drinking water). The evidence is insufficient to conclude that arsenic is associated with diabetes in lower exposure (< 150 μg arsenic/L drinking water), although recent studies with better measures of outcome and exposure support an association. The animal literature as a whole was inconclusive; however, studies using better measures of diabetes-relevant end points support a link between arsenic and diabetes.
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•Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants in humans.•Serum PFAS concentrations may reduce antibody response after vaccination.•We conducted a systematic review and ...meta-analysis of antibody response and PFAS.•An inverse association was found, e.g, −5% per doubling of perfluorooctanoate.•The association was present across antibodies to multiple different antigens.
Epidemiologic studies of serum per- and polyfluoroalkyl substances (PFAS) and antibody response to vaccines have suggested an adverse association, but the consistency and magnitude of this association remain unclear.
The goal of this systematic review was to determine the size of the association between a doubling in perfluoroalkyl substances (PFAS) serum concentration and difference in loge antibody concentration following a vaccine, with a focus on five PFAS: perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA).
We conducted online searches of PubMed and Web of Science through May 17, 2022 and identified 14 eligible reports published from 2012 to 2022.
We included studies conducted in humans, including mother–child pairs, which examined serum PFAS concentration in relation to serum concentration of antibody to a specific antigen following a vaccine.
Study appraisal and synthesis methods: We used the risk of bias assessment for non-randomized studies of exposure and certainty assessment method proposed by Morgan et al. (2019). Using a multilevel meta-regression model, we quantitatively synthesized the data.
The 14 reports represented 13 unique groups of subjects; the frequency of studies of a given antibody was Tetanus (n = 7); followed by Diphtheria (6); Measles (4); Rubella (3); Haemophilus influenzae type b and Influenza A H1N1 (2 each); and Hepatitis A, Hepatitis B, Influenza A H2N3, Influenza B, and Mumps (1 each). There were approximately 4,830 unique participants included in the analyses across the 14 reports. The models of coefficients between antibody concentration and the five principal PFAS showed homogeneity of associations across antibody types for each principal PFAS. In the models with all antibodies treated as one type, evidence of effect modification by life stage was present for PFOA and PFOS, and for consistency, all associations were evaluated for all ages and for children. The summary associations (coefficients for difference in logeantibody concentration per doubling of serum PFAS) with 95% confidence intervals that excluded zero (“statistical support”), and certainty of evidence ratings were as follows: for PFOA and all antibodies treated as one type in all ages, −0.06 (-0.10, −0.01; moderate) and in children, −0.10 (-0.16, −0.03; moderate); for Diphtheria in children, −0.12 (-0.23, −0.00; high); for Rubella in all ages, −0.09 (-0.17, −0.01; moderate), and for Tetanus in children, −0.12 (-0.24, −0.00; moderate). For PFOS the summary associations were, for all antibodies treated as one type in all ages, −0.06 (-0.11, −0.01; moderate) and in children, −0.10 (-0.18, −0.03; moderate); for Rubella in all ages, −0.09 (-0.15, −0.03; high) and in children, −0.12 (-0.20, −0.04; high). For PFHxS the summary associations were, for all antibodies treated as one type in all ages, −0.03 (-0.06, −0.00; moderate) and in children, −0.05 (-0.09, −0.00; low); and for Rubella in children, −0.07 (-0.11, −0.02; high). Summary associations for PFNA and PFDA did not have statistical support, but all PFAS studied tended to have an inverse association with antibody concentrations.
Epidemiologic data on immunosuppression and five principal PFAS suggest an association, with support across antibodies against multiple types of antigens. Data on Diphtheria, Rubella, and Tetanus were more supportive of an association than for other antibodies, and support was greater for associations with PFOA, PFOS, and PFHxS, than for PFNA or PFDA. The data on any specific antibody were scarce. Confounding factors that might account for the relation were not identified. Nearly all studies evaluated were judged to have a low or moderate risk of bias.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is a common cause of liver disease in children and adolescents. The majority of studies of NAFLD in children have been in select ...populations of the clinically obese. Study aims were to estimate the prevalence of elevated alanine aminotransferase (ALT, as a marker of NAFLD) in a general contemporary adolescent population and to identify leading risk factors for ALT elevation (>30 U/L). Methods: We analyzed data of adolescent participants (aged 12–19 years; N = 5586) in the National Health and Nutrition Examination Survey 1999–2004, a representative sample of the civilian noninstitutionalized US population. Results: The prevalence of elevated ALT levels (>30 U/L) was 7.4% among white adolescents, 11.5% among Mexican American adolescents, and 6.0% among black adolescents. Elevated ALT levels were prevalent in 12.4% of male subjects compared with 3.5% of female subjects. Multivariable associations with elevated ALT levels were found for sex (odds ratio OR male vs female, 7.7; 95% confidence interval CI, 3.9–15.1), ethnicity (OR black vs white, 0.6; 95% CI, 0.3–1.3; OR Mexican American vs white, 1.6; 95% CI, 1.0–2.6), waist circumference (OR per 1 SD, 1.4; 95% CI, 1.0–2.0), and fasting insulin level (OR per 1 SD, 1.6; 95% CI, 1.2–2.1). Age, C-reactive protein levels, and triglyceride levels were also positively and socioeconomic position inversely associated with elevated ALT levels. The magnitude of associations were similar across ethnic groups. Conclusions: ALT level is associated with waist circumference and insulin resistance even in a young population. These characteristics could be utilized to identify adolescents who may benefit from screening for NAFLD, offering an opportunity to prevent disease progression at an early age.
Prenatal exposure to bisphenol A (BPA) has been associated with adverse birth outcomes, but findings of previous studies have been inconsistent.
We investigated the relation of prenatal BPA exposure ...with intrauterine growth and evaluated the effect of the number of measurements per subject on observed associations.
This study was embedded in a Dutch population-based prospective cohort study, with urine samples collected during early, mid-, and late pregnancy. The study comprised 219 women, of whom 99 had one measurement, 40 had two measurements, and 80 had three measurements of urinary BPA. Fetal growth characteristics were repeatedly measured by ultrasound during pregnancy and combined with measurements at birth. Linear regression models for repeated measurements of both BPA and fetal growth were used to estimate associations between urinary concentrations of creatinine-based BPA (BPACB) and intrauterine growth.
The relationship between BPACB and fetal growth was sensitive to the number of BPA measurements per woman. Among 80 women with three BPA measurements, women with BPACB > 4.22 μg/g crea (creatinine) had lower growth rates for fetal weight and head circumference than did women with BPACB < 1.54 μg/g crea, with estimated differences in mean values at birth of -683 g (20.3% of mean) and -3.9 cm (11.5% of mean), respectively. When fewer measurements were available per woman, the exposure-response relationship became progressively attenuated and statistically nonsignificant.
Our findings suggest that maternal urinary BPA may impair fetal growth. Because previous studies have shown contradictory findings, further evidence is needed to corroborate these findings in the general population.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The relationship of maternal glomerular filtration rate (GFR) in pregnancy to fetal size needs to be better characterized as it impacts an ongoing debate about confounding effect of maternal GFR in ...investigations of important environmental contaminants. We aimed to characterize the size of the association between maternal GFR and infant birth weight.
A sub-cohort of 953 selected women (470 women with and 483 women without preeclampsia) in the Norwegian Mother and Child Cohort (MoBa), recruited during 2003-2007 were analyzed. GFR in the second trimester was estimated based on plasma creatinine. Birth weight was ascertained from the Medical Birth Registry of Norway. Multivariate linear regression was used to evaluate the association between maternal GFR in second trimester (estimated by the Cockroft-Gault GFR-CG and the modification of diet in renal disease GFR-MDRD formulas) and infant birth weight. Partial correlation coefficients were also calculated.
Maternal GFR-CG (β: 0.73 g/ml/min, p = 0.04) and GFR-MDRD (β: 0.83 g/ml/min, p = 0.04) were associated with infant birth weight in models adjusted for maternal weight in kilograms, preeclampsia, and gestational age at delivery (days). Partial correlation coefficients for the association between infant birth weight and GFR were 0.07 for both formulas. Although the birth weight-GFR association was stronger among the women with preeclampsia, the difference from women without preeclampsia was not statistically significant.
These data support an association between GFR during pregnancy and infant birth weight, and indicate that GFR may confound selected epidemiologic associations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Perfluoroalkyl substances (PFASs) are synthetic compounds that are widely used in industry and are often detectable in humans. In pregnant rats and their pups, PFASs can interfere with thyroid ...hormone homeostasis. In humans, maternal thyroid hormones supply the fetus throughout pregnancy, and thyroid hormones play a critical role in fetal growth and neurodevelopment.
We investigated the association between maternal PFAS exposure and thyroid hormone status in pregnant women and neonates.
In a study of environmental exposure and health in Taiwan, we measured serum concentrations of nine PFASs and four thyroid hormones for 285 pregnant women in their third trimester, and also measured cord serum thyroid hormones for 116 neonates. Associations between maternal PFASs and maternal and cord thyroid hormones were examined in multiple linear regression models.
Perfluorohexanesulfonic acid concentrations were positively associated with maternal thyroid-stimulating hormone (TSH) levels. Pregnant women with higher levels of perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) had lower free thyroxine (T4) and total T4 levels. For example, we estimated that maternal free T4 levels decreased 0.019 ng/dL (95% CI: -0.028, -0.009) with each nanogram per milliliter increase in maternal PFNA. Finally, maternal PFNA, PFUnDA, and PFDoDA levels were associated with lower cord total triiodothyronine (T3) and total T4 levels, and maternal perfluorodecanoic acid (PFDeA) was associated with lower cord total T3.
Our results suggest that exposure to some PFASs during pregnancy may interfere with thyroid hormone homeostasis in pregnant women and fetuses.
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CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Prenatal exposure to organophosphate (OP) pesticides has been associated with altered neuronal cell development and behavioral changes in animal offspring. However, the few studies investigating the ...association between prenatal OP pesticide exposure and neurodevelopmental outcomes such as Attention-Deficit Hyperactivity Disorder (ADHD) and autistic traits in children produced mixed findings.
The objective of the present study was to examine whether maternal urinary concentrations of OP pesticide metabolites are associated with ADHD and autistic traits in children participating in the Generation R Study, a population-based birth cohort from Rotterdam, the Netherlands.
Maternal concentrations of 6 dialkylphosphates (DAPs) were measured using gas chromatography coupled with tandem mass spectrometry in urine samples collected at <18 weeks, 18‐25 weeks, and > 25 weeks of gestation in 784 mother-child pairs. DAP metabolite concentrations were expressed as molar concentrations divided by creatinine levels and log10 transformed. ADHD traits were measured at ages 3, 6, and 10 years using the Child Behavior Checklist (CBCL) (n = 781) and autistic traits were measured at age 6 years using the Social Responsiveness Scale (SRS) (n = 622). First, regression models were fit for the averaged prenatal exposure across pregnancy. Second, we investigated associations for each collection phase separately, and applied a mutually adjusted model in which the effect of prenatal DAP concentrations from each time period on ADHD and autistic traits were jointly estimated. All associations were adjusted for relevant confounders.
Median DAP metabolite concentration was 309 nmol/g creatinine at <18 weeks, 316 nmol/g creatinine at 18–25 weeks, and 308 nmol/g creatinine at >25 weeks of gestation. Overall, DAP metabolite concentrations were not associated with ADHD traits. For instance, a log10 increase in averaged total DAP concentrations across gestation was not associated with a lower ADHD score (-0.03 per SD 95 CI: −0.28 to 0.23). Similarly, no associations between maternal DAP concentrations and autistic traits were detected.
In this study of maternal urinary DAP metabolite concentrations during pregnancy, we did not observe associations with ADHD and autistic traits in children. These are important null observations because of the relatively high background DAP concentrations across pregnancy, the relatively large sample size, and the 10-year follow-up of the offspring. Given the measurement error inherent in our OP pesticide exposure biomarkers, future studies using more urine samples are needed to accurately measure OP pesticide exposure over pregnancy in relation to ADHD and autistic traits.
•We explored whether prenatal exposure to OP pesticides is associated with ADHD and autistic traits in children•Maternal urinary concentrations of six DAP metabolites were measured during early, mid, and late pregnancy•DAP metabolite concentrations in this study were 2-3 times higher compared with concentrations measured in most other studies•Maternal DAP concentrations were not associated with ADHD and autistic traits in children.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP