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1.
Artigo em Inglês | MEDLINE | ID: mdl-31444118

RESUMO

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a chemical class widely used in industrial and commercial applications because of their unique physical and chemical properties. Between 2013 and 2016 PFAS were detected in public water systems and private wells in El Paso County, Colorado. The contamination was likely due to aqueous film forming foams used at a nearby Air Force base. OBJECTIVE: To cross-sectionally describe the serum concentrations of PFAS in a highly exposed community, estimate associations with drinking water source, and explore potential demographic and behavioral predictors. METHODS: In June 2018, serum PFAS concentrations were quantified and questionnaires administered in 213 non-smoking adult (ages 19-93) participants residing in three affected water districts. Twenty PFAS were quantified and those detected in >50% of participants were analyzed: perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA) and perfluoroheptane sulfonate (PFHpS). Unadjusted associations were estimated between serum PFAS concentrations and several predictors, including water consumption, demographics, personal behaviors and employment. A multiple linear regression model estimated adjusted associations with smoking history. RESULTS: Study participants' median PFHxS serum concentration (14.8 ng/mL) was approximately 12 times as high as the U.S. national average. Median serum concentrations for PFOS, PFOA, PFNA and PFHpS were 9.7 ng/mL, 3.0 ng/mL, 0.4 ng/mL and 0.2 ng/mL, respectively. Determinants of PFHxS serum concentrations were water district of residence, frequency of bottled water consumption, age, race/ethnicity, and smoking history. Determinants of serum concentrations for the other four PFAS evaluated included: water district of residence, bottled water consumption, age, sex, race/ethnicity, smoking history, and firefighter or military employment. CONCLUSIONS: Determinants of serum concentrations for multiple PFAS, including PFHxS, included water district of residence and frequency of bottled water consumption. Participants' dominant PFAS exposure route was likely consumption of PFAS-contaminated water, but certain demographic and behavioral characteristics also predicted serum concentrations.

2.
Diabetologia ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444527

RESUMO

AIMS/HYPOTHESIS: We previously showed that intrauterine exposure to gestational diabetes mellitus (GDM) increases selected markers of adiposity in pre-pubertal adolescents. In the present study, we examined these associations in adolescence, and explored whether they are strengthened as the participants transition through puberty. METHODS: Data from 597 individuals (505 unexposed, 92 exposed) participating in the longitudinal Exploring Perinatal Outcomes among Children (EPOCH) study in Colorado were collected at two research visits when the participants were, on average, 10.4 and 16.7 years old. Adiposity measures included BMI, waist/height ratio, and visceral and subcutaneous adipose tissue (as determined by MRI). Separate general linear mixed models were used to assess the longitudinal relationships between exposure to maternal GDM and each adiposity outcome. We tested whether the effect changed over time by including an interaction term between exposure and age in our models, and whether the associations were explained by postnatal behaviours. RESULTS: Compared with unexposed participants, those exposed to maternal GDM had higher BMI (ß = 1.28; 95% CI 0.35, 2.21; p < 0.007), waist/height ratio (ß = 0.03; 95% CI 0.01, 0.04; p = 0.0004), visceral adipose tissue (ß = 4.81; 95% CI 1.08, 8.54; p = 0.01) and subcutaneous adipose tissue (ß = 35.15; 95% CI 12.43, 57.87; p < 0.003). The magnitude of these differences did not change over time and the associations did not appear to be explained by postnatal behaviours. CONCLUSIONS/INTERPRETATION: Our data provide further evidence that intrauterine exposure to maternal GDM is associated with increased offspring adiposity, an effect that appears early in life and tracks throughout adolescence. Efforts to prevent childhood obesity following intrauterine exposure to maternal GDM should target the prenatal or early life periods.

3.
Environ Int ; 131: 104983, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31284113

RESUMO

BACKGROUND: Prenatal exposures to certain per- and polyfluoroalkyl substances (PFAS) have been linked to lower weight and adiposity at birth but greater weight and adiposity in childhood. We hypothesized that faster growth in early infancy may be associated with maternal PFAS concentrations. METHODS: Among 415 mother-infant pairs in a longitudinal cohort study, we estimated associations between maternal pregnancy serum concentrations of six PFAS and offspring weight and adiposity at ~5 months of age, and growth in early infancy. Linear and logistic regression models were adjusted for potential confounders including maternal pre-pregnancy body mass index. Effect modification by infant sex was evaluated. We evaluated potential confounding by correlated exposures via multipollutant linear regression and elastic net penalized regression. RESULTS: Associations between maternal PFAS concentrations and infant weight and adiposity differed by offspring sex. In male infants, maternal perfluorooctanoate and perfluorononanoate were positively associated with adiposity, with percent fat mass increases of 1.5-1.7% per ln-ng/mL increase in PFAS (median adiposity at ~5 months: 24.6%). Maternal perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were associated with lower weight-for-age z-score among female infants only (-0.26 SD per ln-ng/mL PFOS, 95% CI -0.43, -0.10; -0.17 SD per ln-ng/mL PFHxS, 95% CI -0.33, -0.01). In analyses pooled by sex, 2-(N-methyl-perfluorooctane sulfonamido) acetate above vs. below the limit of detection was associated with greater odds of rapid growth in weight-for-age (odds ratio [OR] 2.2, 95% CI 1.1, 4.3) and weight-for-length (OR 3.3, 95% CI 1.8, 6.2). Multipollutant models generally confirmed the results and strengthened some associations. DISCUSSION: We observed sex- and chemical-specific associations between maternal serum PFAS concentrations and infant weight and adiposity. Multipollutant models suggested confounding by correlated PFAS with opposing effects. Although maternal PFAS concentrations are inversely associated with infant weight and adiposity at birth, rapid gain may occur in infancy, particularly in fat mass.

4.
Hypertension ; 74(2): 375-383, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31230546

RESUMO

Hypertensive disorders of pregnancy (HDP) are associated with low birth weight, shorter gestational age, and increased risk of maternal and offspring cardiovascular diseases later in life. The mechanisms involved are poorly understood, but epigenetic regulation of gene expression may play a part. We performed meta-analyses in the Pregnancy and Childhood Epigenetics Consortium to test the association between either maternal HDP (10 cohorts; n=5242 [cases=476]) or preeclampsia (3 cohorts; n=2219 [cases=135]) and epigenome-wide DNA methylation in cord blood using the Illumina HumanMethylation450 BeadChip. In models adjusted for confounders, and with Bonferroni correction, HDP and preeclampsia were associated with DNA methylation at 43 and 26 CpG sites, respectively. HDP was associated with higher methylation at 27 (63%) of the 43 sites, and across all 43 sites, the mean absolute difference in methylation was between 0.6% and 2.6%. Epigenome-wide associations of HDP with offspring DNA methylation were modestly consistent with the equivalent epigenome-wide associations of preeclampsia with offspring DNA methylation (R2=0.26). In longitudinal analyses conducted in 1 study (n=108 HDP cases; 550 controls), there were similar changes in DNA methylation in offspring of those with and without HDP up to adolescence. Pathway analysis suggested that genes located at/near HDP-associated sites may be involved in developmental, embryogenesis, or neurological pathways. HDP is associated with offspring DNA methylation with potential relevance to development.

5.
Nat Commun ; 10(1): 1893, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015461

RESUMO

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10-7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10-74) and BMI in pregnancy (3/914, p = 1.13x10-3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.


Assuntos
Peso ao Nascer/genética , DNA/metabolismo , Epigênese Genética , Genoma Humano , Adolescente , Adulto , Índice de Massa Corporal , Criança , Ilhas de CpG , DNA/genética , Metilação de DNA , Feminino , Desenvolvimento Fetal/genética , Feto , Ácido Fólico/sangue , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fumar/efeitos adversos , Fumar/sangue , Fumar/genética
6.
Int J Obes (Lond) ; 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30341407

RESUMO

BACKGROUND: Previous studies have modeled the association between fetal exposure to tobacco smoke and body mass index (BMI) growth trajectories, but not the timing of catch-up growth. Research on fetal exposure to maternal secondhand smoking is limited. OBJECTIVES: To explore the associations between fetal exposure to maternal active and secondhand smoking with body composition at birth and BMI growth trajectories through age 3 years. METHODS: We followed 630 mother-child pairs enrolled in the Healthy Start cohort through age 3 years. Maternal urinary cotinine was measured at ~ 27 weeks gestation. Neonatal body composition was measured using air displacement plethysmography. Child weight and length/height were abstracted from medical records. Linear regression models examined the association between cotinine categories (no exposure, secondhand smoke, active smoking) with weight, fat mass, fat-free mass, and percent fat mass at birth. A mixed-effects regression model estimated the association between cotinine categories and BMI. RESULTS: Compared to unexposed offspring, birth weight was significantly lower among offspring born to active smokers (-343-g; 95% CI: -473, -213), but not among offspring of women exposed to secondhand smoke (-47-g; 95% CI: -130, 36). There was no significant difference in the rate of BMI growth over time between offspring of active and secondhand smokers (p = 0.58). Therefore, our final model included a single growth rate parameter for the combined exposure groups of active and secondhand smokers. The rate of BMI growth for the combined exposed group was significantly more rapid (0.27 kg/m2 per year; 95% CI: 0.05, 0.69; p < 0.01) than the unexposed. CONCLUSIONS: Offspring prenatally exposed to maternal active or secondhand smoking experience rapid and similar BMI growth in the first three years of life. Given the long-term consequences of rapid weight gain in early childhood, it is important to encourage pregnant women to quit smoking and limit their exposure to secondhand smoke.

7.
Environ Res ; 162: 308-317, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29407762

RESUMO

BACKGROUND: Phthalates and phenols are suspected endocrine disrupting chemicals that may adversely impact fetal outcomes following in utero exposure. Understanding predictors of exposure to phthalates and phenols during the prenatal period is important. METHODS: We measured urinary concentrations of 15 phthalate metabolites and 11 phenols in 446 pregnant women enrolled in the Healthy Start pre-birth cohort. Creatinine-adjusted geometric means (GM) for each urinary biomarker were compared across categories of potential sociodemographic and dietary predictors. To assess the independent relationship between each significant food group predictor and biomarker we used multivariable models, adjusted for sociodemographic predictors. RESULTS: The phthalate metabolites with the highest concentrations were monoethyl phthalate (GM: 41.1µg/g creatinine) and monocarboxyisooctyl phthalate (GM: 20.5µg/g creatinine). Benzophenone-3 (GM: 124.6µg/g creatinine) and methyl paraben (GM: 119.9µg/g creatinine) were the phenols with the highest concentrations. Concentrations of the metabolites of di-n-butyl phthalate and di(2-ethylhexyl) phthalate were significantly higher in younger, unmarried or unemployed mothers, those who were overweight or obese, those with lower educational attainment, or those of minority race/ethnicity (p-values < 0.05). Metabolites of di-n-butyl phthalate concentrations were 18% lower in those who consumed milk ≥ 7 times per week (95% CI: 30-4%). Benzophenone-3 and triclosan concentrations were significantly higher in older, married, or employed mothers, those with normal body mass index, higher educational attainment, higher household income, or who were non-Hispanic white (p-values < 0.05). Benzophenone-3 concentrations were 62% higher in those who consumed seafood ≥ 5 times per month (95% CI: 16-127%). CONCLUSIONS: We observed differences in urinary concentrations of phthalates and phenol biomarkers by sociodemographic predictors in an ethnically diverse cohort of pregnant women. These results and future analyses from this prospective cohort will help inform targeted interventions to reduce exposure to these potential endocrine disrupting chemicals during pregnancy.

8.
J Pediatr ; 195: 121-127.e2, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29217099

RESUMO

OBJECTIVE: To evaluate the association between dietary inflammatory index (DII) scores during pregnancy and neonatal adiposity. STUDY DESIGN: The analysis included 1078 mother-neonate pairs in Healthy Start, a prospective prebirth cohort. Diet was assessed using repeated 24-hour dietary recalls. DII scores were obtained by summing nutrient intakes, which were standardized to global means and multiplied by inflammatory effect scores. Air displacement plethysmography measured fat mass and fat-free mass within 72 hours of birth. Linear and logistic models evaluated the associations of DII scores with birth weight, fat mass, fat-free mass, and percent fat mass, and with categorical outcomes of small- and large-for-gestational age. We tested for interactions with prepregnancy BMI and gestational weight gain. RESULTS: The interaction between prepregnancy BMI and DII was statistically significant for birth weight, neonatal fat mass, and neonatal percent fat mass. Among neonates born to obese women, each 1-unit increase in DII was associated with increased birth weight (53 g; 95% CI, 20, 87), fat mass (20 g; 95% CI, 7-33), and percent fat mass (0.5%; 95% CI, 0.2-0.8). No interaction was detected for small- and large-for-gestational age. Each 1-unit increase in DII score was associated a 40% increase in odds of a large-for-gestational age neonate (1.4; 95% CI, 1.0-2.0; P = .04), but not a small-for-gestational age neonate (1.0; 95% CI, 0.8-1.2; P = .80). There was no evidence of an interaction with gestational weight gain. CONCLUSIONS: Our findings support the hypothesis that an increased inflammatory milieu during pregnancy may be a risk factor for neonatal adiposity. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02273297.

9.
Environ Health Perspect ; 125(6): 067016, 2017 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-28669937

RESUMO

BACKGROUND: Certain perfluoroalkyl and polyfluoroalkyl substances (PFAS) are widespread, persistent environmental contaminants. Prenatal PFAS exposure has been associated with lower birth weight; however, impacts on body composition and factors responsible for this association are unknown. OBJECTIVES: We aimed to estimate associations between maternal PFAS concentrations and offspring weight and adiposity at birth, and secondarily to estimate associations between PFAS concentrations and maternal glucose and lipids, and to evaluate the potential for these nutrients to mediate associations between PFAS and neonatal outcomes. METHODS: Within the Healthy Start prospective cohort, concentrations of 11 PFAS, fasting glucose, and lipids were measured in maternal mid-pregnancy serum (n=628). Infant body composition was measured using air displacement plethysmography. Associations between PFAS and birth weight and adiposity, and between PFAS and maternal glucose and lipids, were estimated via linear regression. Associations were decomposed into direct and indirect effects. RESULTS: Five PFAS were detectable in >50% of participants. Maternal perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) concentrations were inversely associated with birth weight. Adiposity at birth was approximately 10% lower in the highest categories of PFOA, PFNA, and perfluorohexane sulfonate (PFHxS) compared to the lowest categories. PFOA, PFNA, perfluorodecanoate (PFDeA), and PFHxS were inversely associated with maternal glucose. Up to 11.6% of the effect of PFAS on neonatal adiposity was mediated by maternal glucose concentrations. Perfluorooctane sulfonate (PFOS) was not significantly associated with any outcomes studied. CONCLUSIONS: Follow-up of offspring will determine the potential long-term consequences of lower weight and adiposity at birth associated with prenatal PFAS exposure. https://doi.org/10.1289/EHP641.


Assuntos
Adiposidade/fisiologia , Poluentes Ambientais/sangue , Fluorcarbonetos/sangue , Exposição Materna/estatística & dados numéricos , Obesidade Pediátrica/epidemiologia , Adulto , Ácidos Alcanossulfônicos , Caprilatos , Jejum , Feminino , Glucose , Humanos , Recém-Nascido , Masculino , Gravidez , Estudos Prospectivos
10.
BMC Bioinformatics ; 18(1): 344, 2017 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-28724417

RESUMO

BACKGROUND: In mediation analysis if unmeasured confounding is present, the estimates for the direct and mediated effects may be over or under estimated. Most methods for the sensitivity analysis of unmeasured confounding in mediation have focused on the mediator-outcome relationship. RESULTS: The Umediation R package enables the user to simulate unmeasured confounding of the exposure-mediator, exposure-outcome, and mediator-outcome relationships in order to see how the results of the mediation analysis would change in the presence of unmeasured confounding. We apply the Umediation package to the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) study to examine the role of unmeasured confounding due to population stratification on the effect of a single nucleotide polymorphism (SNP) in the CHRNA5/3/B4 locus on pulmonary function decline as mediated by cigarette smoking. CONCLUSIONS: Umediation is a flexible R package that examines the role of unmeasured confounding in mediation analysis allowing for normally distributed or Bernoulli distributed exposures, outcomes, mediators, measured confounders, and unmeasured confounders. Umediation also accommodates multiple measured confounders, multiple unmeasured confounders, and allows for a mediator-exposure interaction on the outcome. Umediation is available as an R package at https://github.com/SharonLutz/Umediation A tutorial on how to install and use the Umediation package is available in the Additional file 1.


Assuntos
Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores de Confusão (Epidemiologia) , Estudo de Associação Genômica Ampla , Humanos , Análise de Componente Principal , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/patologia , Software
11.
Am J Clin Nutr ; 106(2): 559-567, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28659296

RESUMO

Background: Despite widespread use of weight- and length-based anthropometric indexes as proxies for adiposity, little is known regarding the extent to which they correspond with fat mass (FM) or fat-free mass (FFM) during infancy.Objective: This study aimed to examine associations of 3 derived indicators-weight-for-age z score (WFAZ), weight-for-length score (WFLZ), and body mass index z score (BMIZ)-with FM, percentage of FM, and FFM measured by air-displacement plethysmography during the first 5 mo of life.Design: Applying prospectively collected data from 1027 infants in a Colorado prebirth cohort, we used multivariate regression to evaluate associations between the derived indicators and body composition at birth and at 5 mo, and with change (Δ) during follow-up.Results: At birth, all 3 derived indicators were more strongly associated with FFM than with FM. Each unit of WFAZ corresponded with 0.342 kg FFM (95% CI: 0.331, 0.351 kg FFM), compared with 0.121 kg FM (95% CI: 0.114, 0.128 kg FM) (P < 0.0001); similar trends were observed for WFLZ and BMIZ. By 5 mo, WFLZ and BMIZ were more strongly associated with FM than with FFM, whereas WFAZ correlated similarly with the 2 components of body composition. ΔWFLZ and ΔBMIZ were both more strongly related to ΔFM than to ΔFFM; however, a direct comparison of the 2 indexes with respect to change in the percentage of FM indicated that ΔBMIZ was the optimal proxy of adiposity gain (P < 0.0001, pairwise difference).Conclusions: Weight- and length-based indexes are poor surrogates for newborn adiposity. However, at 5 mo, WFLZ and BMIZ are suitable proxies of FM. When assessing adiposity gain, ΔBMIZ is the best indicator of fat accrual during the first 5 postnatal months. This trial was registered at clinicaltrials.gov as NCT02273297.


Assuntos
Tecido Adiposo/metabolismo , Adiposidade , Composição Corporal , Compartimentos de Líquidos Corporais/metabolismo , Índice de Massa Corporal , Peso Corporal , Obesidade/metabolismo , Adulto , Antropometria , Biomarcadores , Peso ao Nascer , Estatura , Estudos de Coortes , Colorado , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estado Nutricional , Obesidade/etiologia , Pletismografia , Gravidez , Ganho de Peso , Adulto Jovem
12.
J Nutr ; 147(7): 1334-1339, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28539412

RESUMO

Background: Maternal dietary intake during pregnancy may influence offspring growth and adiposity. Specific dietary patterns associated with newborn adiposity have not been identified.Objective: We aimed to identify patterns of maternal dietary intake associated with gestational weight gain (GWG) and fasting glucose during pregnancy and to evaluate whether adherence to these patterns is associated with newborn adiposity.Methods: In the Healthy Start prospective cohort, dietary intake during pregnancy was assessed via 24-h recalls. Reduced-rank regression identified dietary patterns predictive of GWG and fasting glucose. Associations between dietary patterns and newborn fat mass, fat-free mass, and adiposity were estimated by using linear regression models among 764 ethnically diverse mother-infant pairs.Results: Two dietary patterns were identified. Pattern 1, correlated with greater GWG (r = 0.22, P < 0.01), was characterized by a higher consumption of poultry, nuts, cheese, fruits, whole grains, added sugars, and solid fats. Greater adherence to pattern 1 (upper compared with lower tertile) predicted a greater newborn fat-free mass (61 g; 95% CI: 12, 110 g) but no difference in fat mass or adiposity. Pattern 2, correlated with greater maternal fasting glucose (r = 0.16, P < 0.01), was characterized by a higher consumption of eggs, starchy vegetables, solid fats, fruits, and nonwhole grains and a lower consumption of dairy foods, dark-green vegetables, and whole grains. Greater adherence to pattern 2 was associated with a greater newborn birth weight (80 g; 95% CI: 15, 145 g), fat mass (33 g; 95% CI: 8, 59 g), and adiposity (0.9%; 95% CI: 0.3%, 1.6%).Conclusions: Among pregnant women, adherence to a dietary pattern characterized by an intake of poultry, nuts, cheese, and whole grains was associated with greater GWG but not maternal fasting glucose or newborn adiposity. Adherence to a pattern characterized by an intake of eggs, starchy vegetables, and nonwhole grains was associated with higher maternal fasting glucose and greater newborn adiposity. Maternal dietary patterns during pregnancy may influence newborn body composition.


Assuntos
Adiposidade/fisiologia , Dieta , Fenômenos Fisiológicos da Nutrição Pré-Natal , Tecido Adiposo , Adulto , Glicemia , Estudos de Coortes , Colorado , Registros de Dieta , Feminino , Glucose/administração & dosagem , Humanos , Recém-Nascido , Gravidez , Ganho de Peso
13.
J Pediatr ; 183: 94-99.e1, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28161200

RESUMO

OBJECTIVE: To examine associations of demographic, perinatal, and infant feeding characteristics with offspring body composition at approximately 5 months of age. STUDY DESIGN: We collected data on 640 mother/offspring pairs from early pregnancy through approximately 5 months of age. We assessed offspring body composition with air displacement plethysmography at birth and approximately 5 months of age. Linear regression analyses examined associations between predictors and fat-free mass, fat mass, and percent fat mass (adiposity) at approximately 5 months. Secondary models further adjusted for body composition at birth and rapid infant growth. RESULTS: Greater prepregnant body mass index and gestational weight gain were associated with greater fat-free mass at approximately 5 months of age, but not after adjustment for fat-free mass at birth. Greater gestational weight gain was also associated with greater fat mass at approximately 5 months of age, independent of fat mass at birth and rapid infant growth, although this did not translate into increased adiposity. Greater percent time of exclusive breastfeeding was associated with lower fat-free mass (-311 g; P < .001), greater fat mass (+224 g; P < .001), and greater adiposity (+3.51%; P < .001). Compared with offspring of non-Hispanic white mothers, offspring of Hispanic mothers had greater adiposity (+2.72%; P < .001) and offspring of non-Hispanic black mothers had lower adiposity (-1.93%; P < .001). Greater adiposity at birth predicted greater adiposity at approximately 5 months of age, independent of infant feeding and rapid infant growth. CONCLUSIONS: There are clear differences in infant body composition by demographic, perinatal, and infant feeding characteristics, although our data also show that increased adiposity at birth persists through approximately 5 months of age. Our findings warrant further research into implications of differences in infant body composition.


Assuntos
Composição Corporal , Índice de Massa Corporal , Inquéritos Epidemiológicos , Saúde Materna , Ganho de Peso/fisiologia , Adulto , Fatores Etários , Peso ao Nascer , Aleitamento Materno , Desenvolvimento Infantil/fisiologia , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Idade Gestacional , Hispano-Americanos/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Masculino , Pletismografia/métodos , Valor Preditivo dos Testes , Gravidez , Medição de Risco , Fatores Sexuais
14.
J Clin Endocrinol Metab ; 101(1): 176-82, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26574956

RESUMO

CONTEXT: Strong evidence suggests that ectopic fat rather than fat mass per se drives risk for type 2 diabetes. Nonetheless, biomarkers of ectopic fat have gone unexplored. OBJECTIVE: To determine the utility of serum lipidomics to predict ectopic lipid deposition. DESIGN: Cross-sectional. SETTING: The Clinical Translational Research Center at the University of Colorado Anschutz Medical Campus. PARTICIPANTS: Endurance-trained athletes (n = 15, 41 ± 0.9 y old; body mass index 24 ± 0.6 kg/m(2)) and obese people with or without type 2 diabetes (n = 29, 42 ± 1.4 y old; body mass index 32 ± 2.5 kg/m(2)). INTERVENTION: Blood sampling and skeletal muscle biopsy. MAIN OUTCOME MEASURES: Multivariable models determined the ability of serum lipids to predict intramuscular (im) lipid accumulation of triacylglycerol (TAG), diacylglycerol (DAG), and ceramide (liquid chromatography tandem mass spectroscopy). RESULTS: Among people with obesity, serum ganglioside C22:0 and lactosylceramide C14:0 predicted muscle TAG (overall model R(2) = 0.48), whereas serum DAG C36:1 and free fatty acid (FFA) C18:4 were strong predictors of muscle DAG (overall model R(2) = 0.77), as were serum TAG C58:5, FFA C14:2 and C14:3, phosphotidylcholine C38:1, and cholesterol ester C24:1 to predict muscle ceramide (overall model R(2) = 0.85). Among endurance-trained athletes, serum FFA C14:1 and sphingosine were significant predictors of muscle TAG (overall model R(2) = 0.81), whereas no models could predict intramuscular DAG or ceramide in this group. CONCLUSIONS: Different serum lipids predict intramuscular TAG accumulation in obese people vs athletes. The ability of serum lipidomics to predict intramuscular DAG and ceramide in insulin-resistant humans may prove a new biomarker to determine risk for diabetes.


Assuntos
Tecido Adiposo , Coristoma/metabolismo , Atletas , Biomarcadores , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Feminino , Humanos , Resistência à Insulina/genética , Metabolismo dos Lipídeos , Lipídeos/sangue , Masculino , Metabolômica , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Resistência Física , Adulto Jovem
15.
Environ Int ; 84: 94-106, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26255822

RESUMO

Phthalate esters are man-made chemicals commonly used as plasticizers and solvents, and humans may be exposed through ingestion, inhalation, and dermal absorption. Little is known about predictors of phthalate exposure, particularly in Asian countries. Because phthalates are rapidly metabolized and excreted from the body following exposure, it is important to evaluate whether phthalate metabolites measured at a single point in time can reliably rank exposures to phthalates over a period of time. We examined the concentrations and predictors of phthalate metabolite concentrations among 50 middle-aged women and 50 men from two Shanghai cohorts, enrolled in 1997-2000 and 2002-2006, respectively. We assessed the reproducibility of urinary concentrations of phthalate metabolites in three spot samples per participant taken several years apart (mean interval between first and third sample was 7.5 years [women] or 2.9 years [men]), using Spearman's rank correlation coefficients and intra-class correlation coefficients. We detected ten phthalate metabolites in at least 50% of individuals for two or more samples. Participant sex, age, menopausal status, education, income, body mass index, consumption of bottled water, recent intake of medication, and time of day of collection of the urine sample were associated with concentrations of certain phthalate metabolites. The reproducibility of an individual's urinary concentration of phthalate metabolites across several years was low, with all intra-class correlation coefficients and most Spearman rank correlation coefficients ≤0.3. Only mono(2-ethylhexyl) phthalate, a metabolite of di(2-ethylhexyl) phthalate, had a Spearman rank correlation coefficient ≥0.4 among men, suggesting moderate reproducibility. These findings suggest that a single spot urine sample is not sufficient to rank exposures to phthalates over several years in an adult urban Chinese population.


Assuntos
Ácidos Ftálicos/urina , Adulto , Idoso , Índice de Massa Corporal , China , Creatinina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Plastificantes/metabolismo , Reprodutibilidade dos Testes , Gestão de Riscos , População Urbana
16.
Am J Clin Nutr ; 101(2): 302-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25646327

RESUMO

BACKGROUND: Maternal obesity and weight gain during pregnancy are risk factors for child obesity. Associations may be attributable to causal effects of the intrauterine environment or genetic and postnatal environmental factors. OBJECTIVE: We estimated associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) overall and in early pregnancy, midpregnancy, and late pregnancy with neonatal adiposity. DESIGN: Participants were 826 women enrolled in a Colorado prebirth cohort who delivered term infants (2010-2013). GWG to 39 wk of gestation was predicted by using mixed models, and early pregnancy, midpregnancy, and late pregnancy rates of GWG (0-17, 17-27, and 27 wk to delivery) were calculated from repeated weight measures. Neonatal body composition was measured by using air-displacement plethysmography ≤3 d after birth. RESULTS: Each1-kg/m(2) increase in maternal BMI was associated with increased neonatal fat mass (5.2 g; 95% CI: 3.5, 6.9 g), fat-free mass (7.7 g; 95% CI: 4.5, 10.9 g), and percentage of body fat (0.12%; 95% CI: 0.08%, 0.16%). Each 0.1-kg/wk increase in predicted GWG was associated with increased fat mass (24.0 g; 95% CI: 17.4, 30.5 g), fat-free mass (34.0 g; 95% CI: 21.4, 46.6 g), and percentage of body fat (0.55%; 95% CI: 0.37%, 0.72%). No interaction was detected between BMI and GWG in their effects on neonatal body composition. Early pregnancy, midpregnancy, and late pregnancy rates of GWG were independently associated with fat mass and percentage of body fat. Midpregnancy and late pregnancy GWGs were associated with fat-free mass. An observed GWG that exceeded recommendations was associated with higher neonatal fat mass and fat-free mass but not percentage of body fat relative to adequate GWG. CONCLUSIONS: Maternal prepregnancy BMI and GWG, including period-specific GWG, were positively and independently associated with neonatal adiposity. Associations of early and midpregnancy weight gain with neonatal adiposity support the hypothesis that greater maternal weight gain during pregnancy, regardless of prepregnancy BMI, is directly related to offspring adiposity at birth. The Healthy Start study was registered as an observational study at clinicaltrials.gov as NCT02273297.


Assuntos
Adiposidade , Índice de Massa Corporal , Ganho de Peso , Tecido Adiposo/metabolismo , Adolescente , Adulto , Peso ao Nascer , Composição Corporal , Colorado , Feminino , Humanos , Lactente , Modelos Lineares , Masculino , Obesidade/metabolismo , Pletismografia , Gravidez , Estudos Prospectivos , Fatores de Risco , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto Jovem
17.
Occup Environ Med ; 71(9): 629-35, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24727735

RESUMO

OBJECTIVE: To estimate associations between use of specific agricultural pesticides and incident diabetes in women. METHODS: We used data from the Agricultural Health Study, a large prospective cohort of pesticide applicators and their spouses in Iowa and North Carolina. For comparability with previous studies of farmers, we limited analysis to 13 637 farmers' wives who reported ever personally mixing or applying pesticides at enrolment (1993-1997), who provided complete data on required covariates and diabetes diagnosis and who reported no previous diagnosis of diabetes at enrolment. Participants reported ever-use of 50 specific pesticides at enrolment and incident diabetes at one of two follow-up interviews within an average of 12 years of enrolment. We fit Cox proportional hazards models with age as the time scale and adjusting for state and body mass index to estimate HRs and 95% CIs for each of the 45 pesticides with sufficient users. RESULTS: Five pesticides were positively associated with incident diabetes (n=688; 5%): three organophosphates, fonofos (HR=1.56, 95% CI 1.11 to 2.19), phorate (HR=1.57, 95% CI 1.14 to 2.16) and parathion (HR=1.61, 95% CI 1.05 to 2.46); the organochlorine dieldrin (HR=1.99, 95% CI 1.12 to 3.54); and the herbicide 2,4,5-T/2,4,5-TP (HR=1.59, 95% CI 1.00 to 2.51). With phorate and fonofos together in one model to account for their correlation, risks for both remained elevated, though attenuated compared with separate models. CONCLUSIONS: Results are consistent with previous studies reporting an association between specific organochlorines and diabetes and add to growing evidence that certain organophosphates also may increase risk.


Assuntos
Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Diabetes Mellitus/epidemiologia , Exposição Ocupacional/efeitos adversos , Praguicidas/toxicidade , Cônjuges , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças dos Trabalhadores Agrícolas/epidemiologia , Diabetes Mellitus/etiologia , Feminino , Humanos , Incidência , Iowa/epidemiologia , Pessoa de Meia-Idade , North Carolina/epidemiologia , Organofosfatos/toxicidade , Modelos de Riscos Proporcionais , Adulto Jovem
18.
Am J Epidemiol ; 179(7): 824-33, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24557813

RESUMO

Perfluoroalkyl substances (PFAS) are persistent and ubiquitous environmental contaminants, and human exposure to these substances may be related to preeclampsia, a common pregnancy complication. Previous studies have found serum concentrations of PFAS to be positively associated with pregnancy-induced hypertension and preeclampsia in a population with high levels of exposure to perfluorooctanoate. Whether this association exists among pregnant women with background levels of PFAS exposure is unknown. Using data from the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health, we carried out a study of nulliparous pregnant women enrolled in 2003-2007 (466 cases, 510 noncases) to estimate associations between PFAS concentrations and an independently validated diagnosis of preeclampsia. We measured levels of 9 PFAS in maternal plasma extracted midpregnancy; statistical analyses were restricted to 7 PFAS that were quantifiable in more than 50% of samples. In proportional hazards models adjusted for maternal age, prepregnancy body mass index (weight (kg)/height (m)(2)), educational level, and smoking status, we observed no strongly positive associations between PFAS levels and preeclampsia. We found an inverse association between preeclampsia and the highest quartile of perfluoroundecanoic acid concentration relative to the lowest quartile (hazard ratio = 0.55, 95% confidence interval: 0.38, 0.81). Overall, our findings do not support an increased risk of preeclampsia among nulliparous Norwegian women with background levels of PFAS exposure.


Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/sangue , Fluorcarbonetos/sangue , Pré-Eclâmpsia/sangue , Adolescente , Adulto , Ácidos Alcanossulfônicos/sangue , Caprilatos/sangue , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Ácidos Graxos/sangue , Feminino , Humanos , Noruega , Paridade , Pré-Eclâmpsia/etiologia , Gravidez , Modelos de Riscos Proporcionais , Adulto Jovem
19.
Environ Int ; 62: 104-12, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24189199

RESUMO

BACKGROUND: Perfluoroalkyl substances (PFASs) are widespread and persistent environmental pollutants. Previous studies, primarily among non-pregnant individuals, suggest positive associations between PFAS levels and certain blood lipids. If there is a causal link between PFAS concentrations and elevated lipids during pregnancy, this may suggest a mechanism by which PFAS exposure leads to certain adverse pregnancy outcomes, including preeclampsia. METHODS: This cross-sectional analysis included 891 pregnant women enrolled in the Norwegian Mother and Child (MoBa) Cohort Study in 2003-2004. Non-fasting plasma samples were obtained at mid-pregnancy and analyzed for nineteen PFASs. Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured in plasma. Linear regression was used to quantify associations between each PFAS exposure and each lipid outcome. A multiple PFAS model was also fitted. RESULTS: Seven PFASs were quantifiable in >50% of samples. Perfluorooctane sulfonate (PFOS) concentration was associated with total cholesterol, which increased 4.2mg/dL per inter-quartile shift (95% CI=0.8, 7.7) in adjusted models. Five of the seven PFASs studied were positively associated with HDL cholesterol, and all seven had elevated HDL associated with the highest quartile of exposure. Perfluoroundecanoic acid showed the strongest association with HDL: HDL increased 3.7 mg/dL per inter-quartile shift (95% CI=2.5, 4.9). CONCLUSION: Plasma concentrations of PFASs were positively associated with HDL cholesterol, and PFOS was positively associated with total cholesterol in this sample of pregnant Norwegian women. While elevated HDL is not an adverse outcome per se, elevated total cholesterol associated with PFASs during pregnancy could be of concern if causal.


Assuntos
Poluentes Ambientais/sangue , Lipídeos/sangue , Adulto , Ácidos Alcanossulfônicos/sangue , Colesterol/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Fluorcarbonetos/sangue , Humanos , Modelos Lineares , Mães , Noruega
20.
Environ Health ; 12(1): 76, 2013 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-24010716

RESUMO

BACKGROUND: Perfluoroalkyl substances (PFASs) are a group of highly persistent chemicals that are widespread contaminants in wildlife and humans. Exposure to PFAS affects thyroid homeostasis in experimental animals and possibly in humans. The objective of this study was to examine the association between plasma concentrations of PFASs and thyroid stimulating hormone (TSH) among pregnant women. METHODS: A total of 903 pregnant women who enrolled in the Norwegian Mother and Child Cohort Study from 2003 to 2004 were studied. Concentrations of thirteen PFASs and TSH were measured in plasma samples collected around the 18th week of gestation. Linear regression models were used to evaluate associations between PFASs and TSH. RESULTS: Among the thirteen PFASs, seven were detected in more than 60% of samples and perfluorooctane sulfonate (PFOS) had the highest concentrations (median, 12.8 ng/mL; inter-quartile range [IQR], 10.1 -16.5 ng/mL). The median TSH concentration was 3.5 (IQR, 2.4 - 4.8) µIU/mL. Pregnant women with higher PFOS had higher TSH levels. After adjustment, with each 1 ng/mL increase in PFOS concentration, there was a 0.8% (95% confidence interval: 0.1%, 1.6%) rise in TSH. The odds ratio of having an abnormally high TSH, however, was not increased, and other PFASs were unrelated to TSH. CONCLUSIONS: Our results suggest an association between PFOS and TSH in pregnant women that is small and may be of no clinical significance.


Assuntos
Alcanos/sangue , Exposição Ambiental , Poluentes Ambientais/sangue , Fluorcarbonetos/sangue , Tireotropina/sangue , Adolescente , Adulto , Cromatografia Líquida de Alta Pressão , Estudos Transversais , Monitoramento Ambiental , Feminino , Humanos , Imunoensaio , Modelos Lineares , Noruega , Razão de Chances , Gravidez , Espectrometria de Massas em Tandem , Adulto Jovem
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