Log-transformed Concentrations Research Articles

Sarcopenia in the elderly versus microcirculation, inflammation status, and oxidative stress: A cross-sectional study

Age-related mechanisms of sarcopenia associated with vascular function have been recently suggested. This study compared and tested associations between muscle mass and strength, microcirculation, inflammatory biomarkers, and oxidative stress in older adults classified as sarcopenic and non-sarcopenic. Thirty-three physically inactive individuals (72±7 yrs) were assigned to age-matched sarcopenic (SG) and non-sarcopenic (NSG) groups. Between-group comparisons were performed for appendicular skeletal mass (ASM), handgrip and isokinetic strength, microvascular function and morphology, C-reactive protein, insulin-like growth factor-1, tumor necrosis factor-alpha, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, endothelin-1, and oxidized low-density lipoprotein. ASM and knee isokinetic strength were lower in SG than NSG (P < 0.05). No difference between groups was found for outcomes of microvascular function and morphology, but log-transformed IL-6 concentration was twice greater in SG vs. NSG (P = 0.02). Correlations between ASM index, handgrip and knee isokinetic strength vs. markers of microcirculatory function, capillary diameters, vascular reactivity, and endothelial injury were found only in SG. Decreased ASM index and strength have been associated with microcirculatory profile, indicating that microcirculation impairment may be involved somehow in Sarcopenia development. The inflammation status, particularly elevated IL-6, seems to play an important role in this process.

Racial Disparities in the Heavy Metal Contamination of Urban Soil in the Southeastern United States.

(1) Background: Field monitoring data for addressing the disproportional burden of exposure to soil contamination in communities of minority and low socioeconomic status (SES) are sparse. This study aims to examine the association between soil heavy metal levels, SES, and racial composition. (2) Methods: A total of 423 soil samples were collected in the urban areas of eight cities across six Southern states in the U.S., in 2015. Samples were analyzed using inductively coupled plasma–mass spectrometry (ICP–MS) for eight heavy metals. The association was examined with mixed models with the log-transformed metal concentrations as the dependent variables and rankings of low-income or minority percentages as the explanatory variables. (3) Results: Model results showed that soil metal concentrations were significantly associated with rankings of poverty and minority percentages. The cadmium concentration significantly increased by 4.7% (p-value < 0.01), for every 10 percentiles of increase in poverty rank. For every 10 percentiles of increase in minority rank, the soil concentrations were significantly up (p-values < 0.01) for arsenic (13.5%), cadmium (5.5%), and lead (10.6%). Minority rank had significant direct effects on both arsenic and lead. (4) Conclusions: The findings confirmed elevated heavy metal contamination in urban soil in low-income and/or predominantly minority communities.

Detection of imidacloprid and metabolites in Northern Leopard frog (Rana pipiens) brains

Neonicotinoids are a new type of highly water-soluble insecticide used in agricultural practices to eliminate pests. Neonicotinoids bind almost irreversibly to postsynaptic nicotinic acetylcholine receptors in the central nervous system of invertebrates, resulting in overstimulation, paralysis, and death. Imidacloprid, the most commonly used neonicotinoid, is often transported to nearby wetlands through subsurface tile drains and has been identified as a neurotoxin in several aquatic non-target organisms. The aim of the present study was to determine if imidacloprid could cross the blood-brain barrier in adult Northern Leopard frogs (Rana pipiens) following exposure to 0, 0.1, 1, 5, or 10 μg/L for 21 days. Additionally, we quantified the breakdown product of imidacloprid, imidacloprid-olefin, and conducted feeding trials to better understand how imidacloprid affects foraging behavior over time. Exposure groups had 12 to 313 times more imidacloprid in the brain relative to the control and breakdown products showed a dose-response relationship. Moreover, imidacloprid brain concentrations were approximately 14 times higher in the 10 μg/L treatment compared to the water exposure concentration, indicating imidacloprid can bioaccumulate in the amphibian brain. Reaction times to a food stimulus were 1.5 to 3.2 times slower among treatment groups compared to the control. Furthermore, there was a positive relationship between mean response time and log-transformed imidacloprid brain concentration. These results indicate imidacloprid can successfully cross the blood-brain barrier and bioaccumulate in adult amphibians. Our results also provide insights into the relationship between imidacloprid brain concentration and subsequent altered foraging behavior.

Fasting C-peptide values among adolescents in the National Health and Nutrition Examination Surveys.

To report fasting C-peptide values and variations across demographics in healthy non-diabetic adolescents included in the National Health and Nutrition Examination Surveys (NHANES) dataset. In this analysis, we used fasting C-peptide data from the 1999 to 2004 NHANES dataset for participants aged 12 to <18 years (n=2063). The mean ± SE age of the participants was 14.99 ± 0.06 years. The participants included 992 girls and 1071 boys, and more than 80% of participants had a body mass index (BMI) percentile of <85%. Among boys, the most notable finding was the increase in geometric mean C-peptide level from 0.51 nmol/L at age 12, to 0.65 nmol/L at age 15 years. Among girls, levels fluctuated around a geometric mean of 0.67 nmol/L. Girls had significantly higher mean log-transformed C-peptide concentrations than boys (P < 0.0001) after adjusting for age, race and BMI percentile category. After adjusting for age and BMI percentile category, non-Hispanic Black boys and girls had significantly lower C-peptide levels than non-Hispanic White (P=0.0026 and P=0.0093) and Mexican American boys and girls (P < 0.0001 and P < 0.0001), respectively. Despite these findings, both insulin and homeostatic model assessment of insulin resistance were greater in non-Hispanic Black compared to non-Hispanic White participants. Here we describe fasting C-peptide levels in a non-diabetic adolescent population. These data provide crucial insight into evaluating racial differences in endogenous insulin release and clearance and will provide novel information which can be used in assessing residual β-cell function and response to intervention therapy.

Dose–response relationships between maternal urinary cotinine and placental weight and ratio of placental weight to birth weight: The Japan Environment and Children's Study

IntroductionStudies on the relationship between maternal self-reported smoking status and placental weight report inconsistent results. This study examined the relationships between maternal urinary cotinine concentration and placental weight and the ratio of placental weight to birth weight (PW/BW ratio). The study also examined the relationship between maternal smoking status, as determined by cotinine concentration, with placental weight and with PW/BW ratio, stratified by sex of offspring. MethodsOur analysis used information of 91,049 mother–child pairs enrolled in the Japan Environment and Children's Study. Maternal urinary cotinine concentration was quantified (during the second or third trimester) with high-performance liquid chromatography-tandem mass spectrometry. Using restricted cubic splines, placental weight and PW/BW ratio were plotted against natural log-transformed cotinine concentration. Taking cotinine levels of <0.17 ng/mL, 0.17 to <21.5 ng/mL (natural log-transformed values, −1.77 to 3.07), and ≥21.5 ng/mL as indicative of non-smokers, passive smokers, and active smokers, respectively, the relationships between maternal smoking status and placental weight and PW/BW ratio were examined, adjusting for confounders. ResultsPlacental weight and PW/BW ratio increased with increasing cotinine concentration. After cotinine reached a certain concentration, the placental weight decreased in male offspring whereas it plateaued in female offspring. Compared with not smoking, active smoking during pregnancy significantly increased placental weight and PW/BW ratio. ConclusionPlacental weight responded as an inverted U-shape whereas the PW/BW ratio followed a J-shape with increasing maternal urinary cotinine concentration measured during pregnancy, suggesting exposure to tobacco smoke induces a disproportionate reduction in fetal growth. The effect of tobacco smoke on placental growth varied by sex of offspring.

Urinary phthalate metabolite concentrations are negatively associated with follicular fluid anti-müllerian hormone concentrations in women undergoing fertility treatment.

Exposure to phthalates, endocrine-disrupting chemicals commonly used as plasticizers and in consumer products, has been associated with infertility and premature ovarian failure. Our objective was to investigate whether urinary phthalate metabolite concentrations were associated with pre-ovulatory follicular fluid (FF) anti-müllerian hormone (AMH) concentrations in women undergoing fertility treatment. This cross-sectional analysis included 138 women with urinary phthalate data available in the Environment and Reproductive Health (EARTH) Study (2010-2016) in whom FF AMH concentrations were quantified using a sandwich enzyme-linked immunosorbent assay (ELISA). We also quantified 8 phthalate metabolite concentrations using tandem mass spectrometry in 1-2 urine samples per cycle (total 331 urines) and calculated the cycle-specific geometric mean for each metabolite. We applied cluster-weighted generalized estimating equation models (CWGEE) to evaluate the associations of tertiles of urinary phthalate metabolite concentrations with log-transformed FF AMH concentrations adjusting for potential confounders. Study participants had median age of 34.0years (IQR 32.0, 37.0), 83% were white, and median BMI of 23.1kg/m2 (IQR 21.2, 26.1). The following stimulation protocols were used: luteal phase agonist (70%), antagonist (14%), or flare (16%). Urinary concentrations of select phthalate metabolites were negatively associated with FF AMH. For example, women whose urinary mEOHP was in the lowest tertile (range 0.30-4.04ng/ml) had an adjusted mean FF AMH of 0.72ng/mL (95% CI=0.36, 1.44), compared to women in the highest tertile (range 9.90-235), who had an adjusted mean of 0.24ng/mL (95% CI=0.12-0.48, p<0.05). The negative association between urinary concentrations of certain phthalate metabolites with FF AMH concentrations may have implications for antral follicle recruitment and fertility treatment outcomes.

Bioaccumulation and trophic transfer of organic ultraviolet absorbents in the food web of a freshwater lake: Implications for risk estimation

Organic ultraviolet absorbents (UVAs) are increasingly reported in environmental matrices and organisms. However, available information on the bioaccumulation of UVAs in freshwater species is insufficient and their trophodynamics in lake food webs remain unknown. We measured the concentrations of twelve UVAs in the wild species from Lake Chaohu. Except for UV-320 not detected, the other UVAs were prevalent in the study species and their total concentrations were in the range of 5.44–131 ng/g dry weight, which were comparable to the concentrations reported in other waters. Compound and species-specific accumulations of UVAs in the organisms were observed. In the lake, the log-transformed concentrations of 4-methyl benzylidene camphor, octyl p-dimethylaminobenzoate, UV-326, and UV-327 related significantly to the trophic levels of species separately. The calculated trophic magnification factors (TMFs) of the four UVAs were 3.79, implying trophic magnification, and 0.18, 0.40 and 0.58, suggesting trophic dilution, respectively. These suggested that the magnification potential and the associated risks of individual UVAs in freshwater lake differed. To our knowledge, this is the first report of these TMFs in lake food webs. However, more investigation is needed to characterize their trophodynamic behaviors in lakes because food web characteristics likely affect trophic transfer of these chemicals.

Association Between Cadmium Exposure and Liver Function in Adults in the United States: A Cross-sectional Study.

ObjectivesCadmium is widely used, leading to extensive environmental and occupational exposure. Unlike other organs, for which the harmful and carcinogenic effects of cadmium have been established, the hepatotoxicity of cadmium remains unclear. Some studies detected correlations between cadmium exposure and hepatotoxicity, but others concluded that they were not associated. Thus, we investigated the relationship between cadmium and liver damage in the general population.MethodsIn total, 11 838 adult participants from National Health and Nutrition Examination Survey 1999-2015 were included. Urinary cadmium levels and the following liver function parameters were measured: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), total bilirubin (TB), and alkaline phosphatase (ALP). Linear and logistic regression analyses were performed to assess the associations between urinary cadmium concentrations and each liver function parameter after adjusting for age, sex, race/ethnicity, annual family income, smoking status, alcohol consumption status, physical activity, and body mass index.ResultsThe covariate-adjusted results of the linear regression analyses showed significant positive relationships between log-transformed urinary cadmium levels and each log-transformed liver function parameter, where beta±standard error of ALT, AST, GGT, TB, and ALP were 0.049±0.008 (p<0.001), 0.030±0.006 (p<0.001), 0.093±0.011 (p<0.001), 0.034±0.009 (p<0.001), and 0.040±0.005 (p<0.001), respectively. Logistic regression also revealed statistically significant results. The odds ratios (95% confidence intervals) of elevated ALT, AST, GGT, TB, and ALP per unit increase in log-transformed urinary cadmium concentration were 1.360 (1.210 to 1.528), 1.307 (1.149 to 1.486), 1.520 (1.357 to 1.704), 1.201 (1.003 to 1.438), and 1.568 (1.277 to 1.926), respectively.ConclusionsChronic exposure to cadmium showed positive associations with liver damage.

Abnormal Cardiac Repolarization in Thyroid Diseases: Results of an Observational Study.

Background: The relationship between thyroid function and cardiac disease is complex. Both hypothyroidism and thyrotoxicosis can predispose to ventricular arrhythmia and other major adverse cardiovascular events (MACE), so that a U-shaped relationship between thyroid signaling and the incidence of MACE has been postulated. Moreover, recently published data suggest an association between thyroid hormone concentration and the risk of sudden cardiac death (SCD) even in euthyroid populations with high-normal FT4 levels. In this study, we investigated markers of repolarization in ECGs, as predictors of cardiovascular events, in patients with a spectrum of subclinical and overt thyroid dysfunction.Methods: Resting ECGs of 100 subjects, 90 patients (LV-EF > 45%) with thyroid disease (60 overt hyperthyroid, 11 overt hypothyroid and 19 L-T4-treated and biochemically euthyroid patients after thyroidectomy or with autoimmune thyroiditis) and 10 healthy volunteers were analyzed for Tp-e interval. The Tp-e interval was measured manually and was correlated to serum concentrations of thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and thyroxine (FT4).Results: The Tp-e interval significantly correlated to log-transformed concentrations of TSH (Spearman's rho = 0.30, p < 0.01), FT4 (rho = −0.26, p < 0.05), and FT3 (rho = −0.23, p < 0.05) as well as log-transformed thyroid's secretory capacity (SPINA-GT, rho = −0.33, p < 0.01). Spearman's rho of correlations of JT interval to log-transformed TSH, FT4, FT3, and SPINA-GT were 0.51 (p < 1e−7), −0.45 (p < 1e−5), −0.55 (p < 1e−8), and −0.43 (p < 1e−4), respectively. In minimal multivariable regression models, markers of thyroid homeostasis correlated to heart rate, QT, Tp-e, and JT intervals. Group-wise evaluation in hypothyroid, euthyroid and hyperthyroid subjects revealed similar correlations in all three groups.Conclusion: We observed significant inverse correlations of Tp-e and JT intervals with FT4 and FT3 over the whole spectrum of thyroid function. Our data suggest a possible mechanism of SCD in hypothyroid state by prolongation of repolarization. We do not observe a U-shaped relationship, so that the mechanism of SCD in patients with high FT4 or hyperthyroidism seems not to be driven by abnormalities in repolarization.

Associations between prenatal multiple metal exposure and preterm birth: Comparison of four statistical models

BackgroundExposure to some heavy metals has been demonstrated to be related to the risk of preterm birth (PTB). However, the effects of multi-metal mixture are seldom assessed. Thus, we aimed to investigate the associations of maternal exposure to metal mixture with PTB, and to identify the main contributors to PTB from the mixture. MethodsThe population in the nested case-control study was from a prospective cohort enrolled in Wuhan, China between 2012 and 2014. Eighteen metals were measured in maternal urine collected before delivery. Logistic regression, elastic net regularization (ENET), weighted quantile sum regression (WQSR), and Bayesian kernel machine regression (BKMR) were used to estimate the overall effect and identify important mixture components that drive the associations with PTB. ResultsLogistic regression found naturally log-transformed concentrations of 13 metals were positively associated with PTB after adjusting for the covariates, and only V, Zn, and Cr remained the significantly positive associations when additionally adjusting for the 13 metals together. ENET identified 11 important metals for PTB, and V (β = 0.23) had the strongest association. WQSR determined the positive combined effect of metal mixture on PTB (OR: 1.44, 95%CI: 1.32, 1.57), and selected Cr and V (weighted 0.41 and 0.32, respectively) as the most weighted metals. BKMR analysis confirmed the overall mixture was positively associated with PTB, and the independent effect of V was the most significant. Besides, BKMR showed the non-linear relationships of V and Cu with PTB, and the potential interaction between Zn and Cu. ConclusionApplying different statistical models, the study found that exposure to the metal mixture was associated with a higher risk of PTB, and V was identified as the most important risk factor among co-exposed metals for PTB.

Phthalate and DINCH urinary concentrations across pregnancy and risk of preterm birth

Preconception and prenatal exposure to phthalates has been associated with an increased risk of preterm birth. However, it is unclear whether there are periods of heightened susceptibility during pregnancy. This prospective cohort study included 386 women undergoing fertility treatment who gave birth to a singleton infant during 2005 through 2018. Eleven phthalate metabolites were measured in spot urine samples collected at each trimester. In approximately 50% of participants, two metabolites of 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), a phthalate substitute, were also measured. The molar sum of four di(2-ethylhexyl) phthalate metabolites (∑DEHP) was calculated. We evaluated the associations of mean maternal biomarker concentrations with risk of preterm birth using modified log-binomial models and utilized multiple informant models to compare trimester-specific associations. We examined the relative biomarker concentration across gestation comparing women with preterm birth to women with term delivery using quadratic mixed model. The risk ratio for preterm birth associated with a one-unit increase in the natural log-transformed urinary concentrations of ∑DEHP (mean during pregnancy) was 1.21 (95% confidence interval (CI): 0.84, 1.72). In multiple informant models, these associations were strongest in the third trimester (RR = 1.51; 95% CI: 1.17, 1.95). Estimated mean ∑DEHP concentrations were higher among women with preterm than term delivery, especially late in gestation. Associations with preterm birth were also observed for each of the four individual DEHP metabolites. Detection of cyclohexane-1,2-dicarboxylic acid monocarboxyisooctyl ester (MCOCH), a metabolite of DINCH, appeared to be positively related to preterm birth. In this prospective cohort of subfertile couples, maternal ∑DEHP metabolite concentrations during pregnancy were associated with an increased risk of preterm birth, particularly during late gestation.

Multiple plasma metals, genetic risk and serum complement C3, C4: A gene-metal interaction study

Exposure to metals and metalloids is widely related with human health, and could affect the function of immune system. The complement system links innate and adaptive immunity, and is critically involved in the pathogenesis of inflammatory and immune diseases. The third and fourth components of complement (C3, C4) play key roles in the complement system. However, few studies have examined the relations between multiple metals and complement levels. In this study, based on a total of 2977 participants from the Dongfeng-Tongji cohort, China, we investigated 17 plasma metals and serum C3, C4 levels, and calculated C3/C4-associated genetic risk scores (GRSs) using established single nucleotide polymorphisms. We further explored the potential gene-metal interactions on C3 and C4. After multivariable adjustment, an increment of 10-standard deviation increase in natural log-transformed exposure concentrations of plasma copper was associated with 0.549 (0.489, 0.608) (FDR <0.0001), and 1.146 (0.999, 1.294) (FDR <0.0001) higher natural log-transformed serum C3 and C4 levels, respectively. While each increment of 10-standard deviation of natural log-transformed zinc was associated with a difference of 0.083 (0.024, 0.143) (FDR = 0.049) and 0.007 (−0.138, 0.152) (FDR = 0.935) in log-transformed C3 and C4 levels, respectively. Participants with higher GRS had higher C3 and C4 levels. Furthermore, we found a significant interaction between arsenic exposure and C3-GRS in relation to C3 level (Pinteraction = 0.0096). Our results suggested that plasma arsenic would modify the association between C3 genetic predisposition and serum C3 level. We provide new insight into metals exposure on the human immune system. These findings require replication in future research.

Associations of propylene oxide exposure with fasting plasma glucose and diabetes: Roles of oxidative DNA damage and lipid peroxidation

Whether propylene oxide (PO) exposure is associated with hyperglycemia were rarely explored. We aimed to determine the relationship between PO exposure and glucose metabolism, and potential role of oxidative stress. Among 3294 Chinese urban adults, urinary PO metabolite (N-Acetyl-S-(2-hydroxypropyl)-L-cysteine, 2HPMA), biomarkers of oxidative DNA damage (8-oxo-7,8-dihydro-20-deoxyguanosine, 8-OHdG) and lipid peroxidation (8-isoprostane, 8-iso-PGF2α) in urine were determined. The associations of 2HPMA with 8-OHdG, 8-iso-PGF2α, fasting plasma glucose (FPG), and risk of diabetes were explored. The roles of 8-OHdG and 8-iso-PGF2α on association of 2HPMA with FPG and risk of diabetes were detected. After adjusted for potential confounders, each 1-unit increase in log-transformed concentration of 2HPMA was associated with a 0.15-mmol/L increase in FPG level, and the adjusted OR (95% CI) of diabetes by the associations of log-transformed urinary 2HPMA concentrations was 1.47 (95% CI: 1.03–2.11). Combination effects of 2HPMA with 8-OHdG or 8-iso-PGF2α on risk of diabetes were detected, and elevated 8-iso-PGF2α significantly mediated 34.5% of the urinary 2HPMA-associated FPG elevation. PO exposure was positively associated with FPG levels and risk of diabetes. PO exposure combined with DNA oxidative damage or lipid peroxidation may increase the risk of diabetes, and lipid peroxidation may partially mediate the PO exposure-induced FPG elevation.

Association between serum uric acid and depressive symptoms stratified by low-grade inflammation status

Despite increasing evidence for an association between circulating uric acid (UA) and depression, the directionality of this association remains unclear and is potentially moderated by low-grade inflammation. Thus, the present study aimed to investigate the cross-sectional association between serum UA concentration and depressive symptoms in Korean individuals with and without low-grade inflammation, as measured using serum high-specific C-reactive protein (hs-CRP) levels. The final study sample comprised 4188 participants, aged 19–79 years, from the Korea National Health and Nutrition Examination Study 2016. Data on serum uric acid (UA) concentrations, serum hs-CRP levels, Patient Health Questionnaire-9 (PHQ-9) scores, and relative covariates were retrieved. Negative binomial regression with adjustment for the complex sample design was used to analyze the associations. After adjusting for covariates, log-transformed serum UA concentrations and total PHQ-9 scores were positively associated (incidence rate ratio [IRR] = 1.34 [95% confidence interval [CI] = 1.09–1.66]) for participants without low-grade inflammation and inversely associated (IRR = 0.64 [95% CI = 0.45–0.92]) for participants with low-grade inflammation. In conclusion, the direction of the association between serum UA and depressive symptoms was the opposite in participants with and without low-grade inflammation. The study has the limitation of potential uncontrolled confounders.

Association between Blood Mercury Concentration and Prevalence of Borderline Hypercholesterolemia among Adolescents: The Korea National Health and Nutrition Examination Survey (KNHANES) 2010-2013 and 2016.

There is limited evidence on the association between blood mercury (Hg) concentration and the risk of borderline dyslipidemia in adolescents. Here, we investigated the association between blood Hg concentration and the prevalence of borderline dyslipidemia among Korean adolescents. A total of 1559 participants (806 boys and 753 girls) aged 10–18 years who cross-sectionally enrolled in the Korea National Health and Nutrition Examination Survey (KNHANES) 2010–2013 and 2016 were included in this study. Hg concentrations (µg/L) in whole blood samples were measured. The geometric mean (GM) of the blood Hg concentration was 1.88 µg/L. It showed a 63% higher prevalence of borderline hypercholesterolemia (total cholesterol (TC) 170–199 mg/dL) per unit of natural log-transformed blood Hg concentration in boys (95% CI = 1.10–2.41), but not in girls. When a categorical model was applied, the positive association with the prevalence of borderline hypercholesterolemia was also persistant in boys (OR (95% CI) for 2nd and 3rd tertiles (Hg concentration 1.532–11.761 µg/L) vs. 1st tertile (Hg concentration 0.192–1.531 µg/L): 1.92 (1.19–3.10)), but not in girls. This finding suggests that blood Hg concentration might result in a higher prevalence of borderline hypercholesterolemia among adolescents and more stringent public health actions should be taken for the reduction of Hg exposure to prevent dyslipidemia from early-childhood, despite the need of further study to evaluate a causal relationship between blood Hg concentration and the risk of dyslipidemia.

Using principal component analysis to examine associations of early pregnancy inflammatory biomarker profiles and adverse birth outcomes

Inflammation as a risk factor for preterm birth is well-established. The primary objective of this analysis was to examine whether individual cytokines versus a composite indicator of mid-pregnancy inflammation are significantly associated with risk for adverse birth outcomes. A multi-site prospective study was conducted in a socio-demographically diverse cohort of 610 pregnant participants. At a study visit between 12 and 20 6/7 weeks' gestation, low-grade inflammation was measured via log-transformed serum concentrations of the biomarkers IFN-γ, IL-10, IL-13, IL-6, IL-8, TNF-α, and CRP. Principal component analysis (PCA) was used to identify underlying dimensions of inflammatory activity from the seven biomarkers measured. Gestational age and birth weight at delivery were obtained from medical chart review. The associations between inflammatory profiles and birth outcomes were assessed via linear and logistic regression models. Results were compared with those from individual inflammatory biomarkers, and model fit was assessed using Akaike's Information Criterion (AIC). Principal component analysis analysis yielded a two-factor solution, with the first factor (IF1) composed of IL-8, IL-10, IL-13, IFN-ɣ, and TNF-α, and the second factor (IF2) containing IL-6 and CRP. When adjusted for race, education, BMI, smoking status, gestational age at time of blood draw, and study site, a one standard deviation (SD) increase in IF1 remained significantly associated with a decrease in standardized gestational age (β=-.13, 95% CI: -.21, -.05) and an increase in odds of preterm delivery (OR=1.46, 95% CI: 1.13, 1.88) (Table 3). A one SD increase in IF2 was similarly associated with a decrease in standardized gestational age at delivery (β=-.13, 95% CI: -.23, -.04) and an increase in odds of preterm delivery (OR: 1.46, 95% CI: 1.04, 2.05). Neither IF1 nor IF2 was associated with measures of fetal growth. AIC identified that IL-6 was a slightly better fit for length of gestation compared to either composite measure, though all performed similarly. Independent of known sociodemographic risk factors, an elevated mid-pregnancy inflammatory profile was associated with a nearly 50% increase in odds of preterm delivery. The composite performed similarly to IL-6. These results suggest that maternal low-grade inflammation is a risk factor for preterm delivery, and that mid-pregnancy inflammatory biomarkers may be useful in predicting risk for preterm delivery.

Prenatal phthalate exposure and early childhood wheeze in the SELMA study.

Prenatal maternal phthalate exposure has been associated with wheeze and asthma in children, but results are inconclusive. Previous studies typically assessed exposure in late pregnancy, included only a small number of old phthalates, and assessed outcomes in children aged 5 years or older. We explored associations between 1st trimester prenatal maternal exposure to a wider range of phthalates and wheeze in early childhood. First trimester concentrations of 14 metabolites from 8 phthalates and one alternative plasticizer were quantified in first-morning void urine from 1148 mothers in the Swedish SELMA study. Associations between log-transformed metabolite concentrations and parental reported ever wheeze among 24-month-old children were investigated with logistic regression models adjusted for parental asthma/rhinitis, sex of child, maternal education, smoking, and creatinine. Metabolites of replacement phthalates di-iso-decyl phthalate (DiDP) and di-2-propylheptyl phthalate (DPHP) were associated with increased risk for wheeze (aOR 1.47, 95% CI 1.08-2.01 and aOR 1.49, 95% CI 1.04-2.15, respectively). The associations with DiDP and DPHP were stronger among children whose parents did not have asthma or rhinitis. In this group, wheeze was also associated with metabolites of butyl-benzyl phthalate (BBzP) and di-iso-nonyl phthalate (DiNP). Maternal phthalate exposure during early pregnancy may be a risk factor for wheeze in early childhood, especially among children whose parents do not have asthma or rhinitis symptoms.

Association of Serum Vitamin B6 with All-Cause and Cause-Specific Mortality in a Prospective Study

There is little evidence regarding the association between serum vitamin B6 concentration and subsequent mortality. We aimed to evaluate the association of serum vitamin B6 concentration with all-cause, cardiovascular disease (CVD), and cancer mortality in the general population using data from the National Health and Nutrition Examination Survey (NHANES). Our study examined 12,190 adults participating in NHANES from 2005 to 2010 in the United States. The mortality status was linked to National Death Index (NDI) records up to 31 December 2015. Pyridoxal 5′-phosphate (PLP) is the biologically active form of vitamin B6. Vitamin B6 status was defined as deficient (PLP < 20 nmol/L), insufficient (PLP ≥ 20.0 and <30.0 nmol/L), and sufficient (PLP ≥ 30.0 nmol/L). We established Cox proportional-hazards models to estimate the associations of categorized vitamin B6 concentration and log-transformed PLP concentration with all-cause and cause-specific mortality by calculating hazard ratios (HRs) and 95% confidence intervals (95%CIs). In our study, serum vitamin B6 was sufficient in 70.6% of participants, while 12.8% of the subjects were deficient in vitamin B6. During follow-up, a total of 1244 deaths were recorded, including 294 cancer deaths and 235 CVD deaths. After multivariate adjustment in Cox regression, participants with higher serum vitamin B6 had a 15% (HR = 0.85, 95%CI = 0.77, 0.93) reduced risk of all-cause mortality and a 19% (HR = 0.81, 95%CI = 0.68, 0.98) reduced risk for CVD mortality for each unit increment in natural log-transformed PLP. A higher log-transformed PLP was not significantly associated with a lower risk for cancer mortality. Compared with sufficient vitamin B6, deficient (HR = 1.37, 95%CI = 1.17, 1.60) and insufficient (HR = 1.19, 95%CI = 1.02, 1.38) vitamin B6 level were significantly associated with a higher risk for all-cause mortality. There was no significant association for cause-specific mortality. Participants with higher levels of vitamin B6 had a lower risk for all-cause mortality. These findings suggest that maintaining a sufficient level of serum vitamin B6 may lower the all-cause mortality risk in the general population.

Urinary Metal Mixtures and Hormone Levels during the Menopausal Transition: the Study of Women’s Health Across the Nation (SWAN)

BACKGROUND AND AIM: Epidemiologic studies on associations between metal exposures and sex hormones in women have been limited, and results have been mixed. We assessed associations of urinary metals concentrations with longitudinal serum levels of follicle-stimulating hormone (FSH) and estradiol (E2). METHODS: We examined data from 1,355 women aged 45-56 years at baseline (1999-2000), followed through 2017, from the Study of Women’s Health Across the Nation. Baseline urinary concentrations of 15 metals (arsenic, barium, cadmium, cobalt, cesium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, tin, thallium, and zinc) were determined. Serum levels of FSH and E2 were measured repeatedly over 17 years of follow-up. Linear mixed effects models were used to evaluate associations between individual metals and hormone levels. The least absolute shrinkage and selection operator (LASSO) penalized linear mixed effects models were used to evaluate associations between metal mixtures and hormone levels. An environmental risk score (ERS) was used to integrate metal mixture effects from LASSO results. RESULTS:After adjustment for confounders, one standard deviation increase in log-transformed baseline urinary metal concentrations were associated with 3.53% (95% CI: 0.42%, 6.73%) higher levels of FSH for cadmium, 5.61% (95% CI: 2.50%, 8.82%) higher levels for lead, and 3.06% (95% CI: -5.87%, -0.17%) lower levels for cobalt. For E2 levels, one standard deviation increase in log-transformed urinary metal concentrations were associated with 2.88% (95% CI: -5.31%, -0.38%) lower levels for mercury, 5.20% (95% CI: -7.56%, -2.78%) lower levels for lead, and 2.44% (95% CI: -4.74%, -0.09%) lower levels for tin. The ERS was associated with higher FSH and lower E2 levels. CONCLUSIONS:Results from this prospective cohort study of midlife women suggested that metals, including lead, cadmium, mercury, cobalt, tin, and metal mixtures were associated with serum FSH and E2 levels, consistent with findings that metal exposures affect reproductive aging. KEYWORDS: metals, mixtures, estradiol, follicle-stimulating hormone, cohort study

Increased arsenic levels in both environmental measurements and biomonitoring results are associated with elevated risk of spina bifida

BACKGROUND AND AIM: Arsenic is associated with multiple adverse reproductive outcomes, and previous studies suggested higher risk of neural tube defects among mothers exposed to higher concentration of well water arsenic in Bangladesh. We further examine the association using water arsenic as proxy for external exposure and toenail as biomarkers for internal dose. METHODS: Parental toenail and water arsenic concentrations were examined in a case-control study in National Institute of Neurosciences & Hospital, Dhaka, Bangladesh. The associations between log-transformed and percentile arsenic concentrations and physician-diagnosed spina bifida were evaluated with logistic regression and cluster analysis, adjusted for maternal age, maternal BMI, parity, educational level, folic acid use and second-hand smoke exposure during pregnancy and weighted by self-reported dietary patterns. RESULTS:Median concentration for water, maternal and paternal arsenic are 2.0 ppb, 0.4 and 0.5 microgram per gram toenail among 280 included child-parent trios (156 with spina bifida) with complete exposure data. We observed associations between highest quartile maternal arsenic levels, higher than 10 ppb arsenic in water and spina bifida risk for their children after weighted for diet (Adjusted OR for water arsenic=1.49, 95% CI=1.00-2.06; adjusted OR for maternal arsenic=1.57, 95% CI=1.10-2.24), and higher composite exposure in both hierarchical clustering and k-means clustering were also associated with increased risk after weighting. Effect heterogeneity was observed between different folic acid supplement conditions, in which dose-response was attenuated for both water and paternal concentrations. CONCLUSIONS:Prenatal inorganic arsenic exposure was associated with elevated risk of spina bifida in Bangladesh, and joint parental exposure is associated with a higher risk. Investigations and interventions to mitigate arsenic exposure during for pregnant women are warranted. KEYWORDS: Heavy metals, birth outcomes, children's environmental health