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BACKGROUND: Evidence suggests that prenatal per- and polyfluoroalkyl substances (PFAS) and metals, two classes of chemicals found ubiquitously in human populations, influence immune system development and response. OBJECTIVE: We evaluated whether first trimester blood PFAS and metals were associated with antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion. METHODS: We measured six PFAS, as well as six nonessential and four essential metals, in first trimester blood from participants in the longitudinal pre-birth Project Viva cohort, recruited between 1999 and 2000 in eastern Massachusetts. We measured antigen- or mitogen-stimulated cord blood mononuclear cell proliferation responses (n = 269-314) and cytokine secretion (n = 217-302). We used covariate-adjusted least absolute shrinkage and selection operator (LASSO) for variable selection and multivariable regression to estimate associations with the immune markers. RESULTS: Each ng/mL of MeFOSAA was associated with a 3.6% (1.4, 5.8) higher lymphocyte proliferation response after stimulation with egg antigen, as well as 0.8 (0.7, 1.0) reduced odds of having IFN-γ detected in response to dust mite. Each ng/g increment of cesium was associated with 27.8% (-45.1, -4.9) lower IL-10 levels in response to dust mite. Each ng/g increment of mercury was associated with 12.0% (1.3, 23.8) higher IL-13 levels in response to mitogen PHA. Each ng/g increment of selenium and zinc was associated with 0.2% (0.01, 0.4) and 0.01% (0.002, 0.02) higher TNF-α in response to mitogen PHA, respectively. CONCLUSIONS: Prenatal metals and PFAS influence cord blood lymphocyte proliferation and cytokine secretion in ways that may increase risk for atopic disease in childhood.
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BACKGROUND: Phthalates may adversely influence body composition by lowering anabolic hormones and activating peroxisome-proliferator activated receptor gamma. However, data are limited in adolescence when body mass distributions rapidly change and bone accrual peaks. Also, potential health effects of certain phthalate/replacements [e.g., di-2-ethylhexyl terephthalate (DEHTP)] have not been well studied. METHODS: Among 579 children in the Project Viva cohort, we used linear regression to evaluate associations of urinary concentrations of 19 phthalate/replacement metabolites from mid-childhood (median: 7.6 years; 2007-2010) with annualized change in areal bone mineral density (aBMD) and lean, total fat, and truncal fat mass as measured by dual-energy X-ray absorptiometry between mid-childhood and early adolescence (median: 12.8 years). We used quantile g-computation to assess associations of the overall chemical mixture with body composition. We adjusted for sociodemographics and tested for sex-specific associations. RESULTS: Urinary concentrations were highest for mono-2-ethyl-5-carboxypentyl phthalate [median (IQR): 46.7 (69.1) ng/mL]. We detected metabolites of most replacement phthalates in a relatively small number of participants [e.g., 28% for mono-2-ethyl-5-hydrohexyl terephthalate (MEHHTP; metabolite of DEHTP)]. Detectable (vs. non-detectable) MEHHTP was associated with less bone and greater fat accrual in males and greater bone and lean mass accrual in females [e.g., change in aBMD Z-score/year (95% CI): -0.049 (-0.085, -0.013) in males versus 0.042 (0.007, 0.076) in females; pinteraction<0.01]. Children with higher concentrations of mono-oxo-isononyl phthalate and mono-3-carboxypropyl phthalate (MCPP) had greater bone accrual. Males with higher concentrations of MCPP and mono-carboxynonyl phthalate had greater accrual of lean mass. Other phthalate/replacement biomarkers, and their mixtures, were not associated with longitudinal changes in body composition. CONCLUSIONS: Concentrations of select phthalate/replacement metabolites in mid-childhood were associated with changes in body composition through early adolescence. As use of phthalate replacements such as DEHTP may be increasing, further investigation can help better understand the potential effects of early-life exposures.
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Poluentes Ambientais , Ácidos Ftálicos , Criança , Masculino , Feminino , Humanos , Adolescente , Ácidos Ftálicos/urina , Composição Corporal , Densidade Óssea , Poluentes Ambientais/metabolismo , Exposição AmbientalRESUMO
BACKGROUND: Children are vulnerable to adverse health effects associated with phthalates, and food is one source of exposure. A comprehensive analysis investigating urinary phthalate metabolite concentrations in relation to food type and source has yet to be undertaken. OBJECTIVES: We use reduced rank regression, a dimension reduction method, to identify dietary patterns associated with urinary phthalate metabolites in children in a large US study. METHODS: We used data from 2369 participants 6-19 years old from the 2011-2016 National Health and Nutrition Examination Survey who recalled their diet over the 24 h prior to urine collection. We used dietary data to estimate intake and source (i.e., prepared at a restaurant vs. purchased from a grocery store) of 136 food groups. We used reduced rank regression to identify dietary patterns explaining variation in overall urinary concentrations of ∑di-2-ethylhexyl phthalate and seven phthalate metabolites. We also examined pairwise associations between food groups and urinary phthalate metabolites. RESULTS: We identified eight dietary patterns that cumulatively explained 12.1% of variation in urinary phthalate metabolites, including a dietary pattern characterized by certain starchy vegetables (e.g., plantains and lima beans), quick breads, and citrus juice prepared at a restaurant. A one SD increase in this food pattern score was associated with a 37.2% higher monocarboxyoctyl phthalate (MCOP) concentration (95% CI: 30.3, 44.4). We also observed weak associations between certain food groups and urinary phthalate metabolites (e.g., a one SD increase in intake of certain starchy vegetables prepared at a restaurant was associated with a 1.8% [95% CI: 0.7, 2.8] higher MCOP). CONCLUSIONS: Children whose diets were characterized by higher consumption of certain starchy vegetables, quick breads, and citrus juices prepared at a restaurant had higher urinary phthalate metabolites. More detailed information on the specific methods of food processing and details on packaging materials is needed.
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Poluentes Ambientais , Ácidos Ftálicos , Adolescente , Adulto , Criança , Dieta , Exposição Ambiental , Humanos , Inquéritos Nutricionais , Adulto JovemRESUMO
BACKGROUND: Arsenic exposure has been associated with gestational diabetes mellitus. However, the extent to which arsenic exposure during pregnancy is associated with postpartum glucose intolerance is unknown. METHODS: We studied 323 women in Bangladesh. We assessed arsenic exposure in early pregnancy via toenail and water samples. We measured fasting glucose and insulin in serum at a mean (SD) of 4.0 (3.5) weeks post-delivery. We ran covariate-adjusted, linear regression models to examine associations of arsenic concentrations with HOMA-IR, a marker of insulin resistance, and HOMA-ß, a marker of beta cell function. RESULTS: Median (IQR) arsenic concentration was 0.45 (0.67) µg/g in toenails and 2.0 (6.5) µg/L in drinking water. Arsenic concentrations during pregnancy were not associated with insulin resistance or beta cell function postpartum. HOMA-IR was 0.07% (- 3.13, 3.37) higher and HOMA-ß was 0.96% (- 3.83, 1.99) lower per IQR increment in toenail arsenic, but effect estimates were small and confidence intervals crossed the null. CONCLUSIONS: Although arsenic exposure during pregnancy has been consistently associated with gestational diabetes mellitus, we found no clear evidence for an adverse effect on postpartum insulin resistance or beta cell function.
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Arsênio , Diabetes Gestacional , Arsênio/análise , Bangladesh/epidemiologia , Glicemia , Diabetes Gestacional/induzido quimicamente , Diabetes Gestacional/epidemiologia , Feminino , Glucose , Humanos , Período Pós-Parto , GravidezRESUMO
OBJECTIVE: To investigate the association of preconception parental obesity (body mass index [BMI] ≥30 kg/m2) with offspring pubertal development. STUDY DESIGN: Among 1377 children from a prospective prebirth cohort in Boston, we examined markers of puberty (age at peak height velocity [PHV], age at menarche, self-reported pubertal development score), and adrenarche (pictograph Tanner pubic hair staging). We used multivariable regression models to examine associations of maternal and paternal obesity with offspring pubertal indices, and applied marginal structural models to estimate the controlled direct effect not mediated by offspring prepubertal BMI. RESULTS: The prevalence of paternal obesity alone, maternal obesity alone, and biparental obesity were 10.5%, 10.1%, and 5%, respectively. After adjusting for demographic and socioeconomic factors, parental heights and maternal age at menarche, maternal obesity alone (vs neither parent with obesity) was associated with earlier age at PHV (ß -0.30 years; 95% CI -0.57, -0.03) and higher early adolescent pubertal score (0.29 units; 0.10, 0.48) in boys, but not with pubertal or adrenarchal outcomes in girls. Paternal obesity alone was not associated with any outcomes in either boys or girls. Biparental obesity was associated with earlier age at PHV in boys and earlier menarche in girls. Using marginal structural models with stabilized inverse probability weighting, maternal obesity alone had significant controlled direct effects on age at PHV (-0.31 years; -0.62, 0.00) and on pubertal score (0.22 units; 0.00, 0.44) in boys, independent of prepubertal BMI. CONCLUSION: Maternal, but not paternal, obesity is associated with earlier pubertal development in boys, and such association is independent of prepubertal BMI.
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Deficiências do Desenvolvimento/etiologia , Menarca/fisiologia , Obesidade/epidemiologia , Pais , Maturidade Sexual/fisiologia , Adolescente , Adulto , Fatores Etários , Índice de Massa Corporal , Boston/epidemiologia , Criança , Pré-Escolar , Deficiências do Desenvolvimento/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Idade Materna , Obesidade/complicações , Prevalência , Estudos ProspectivosRESUMO
This Viewpoint describes new maximum contaminant levels set by the Environmental Protection Agency for specific perfluoroalkyl and polyfluoroalkyl substances (PFASs) and discusses the role clinicians can play in addressing their patients' PFAS health concerns.
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Associations of prenatal exposure to perfluoroalkyl substances (PFAS), ubiquitous chemicals used in stain- and water-resistant products, with adverse birth outcomes may be confounded by pregnancy hemodynamics. We measured plasma concentrations of 4 PFAS in early pregnancy (median length of gestation, 9 weeks) among 1,645 women in Project Viva, a study of a birth cohort recruited during 1999-2002 in eastern Massachusetts. We fitted multivariable models to estimate associations of PFAS with birth weight-for-gestational age z score and length of gestation, adjusting for sociodemographic confounders and 2 hemodynamic markers: 1) plasma albumin concentration, a measure of plasma volume expansion, and 2) plasma creatinine concentration, used to estimate glomerular filtration rate. Perfluorooctane sulfonate (PFOS) and perfluorononanoate (PFNA) were weakly inversely associated with birth weight-for-gestational age z scores (adjusted ß = -0.04 (95% confidence interval (CI): -0.08, 0.01) and adjusted ß = -0.06 (95% CI: -0.11, -0.01) per interquartile-range increase, respectively). PFOS and PFNA were also associated with higher odds of preterm birth (e.g., for highest PFOS quartile vs. lowest, adjusted odds ratio = 2.4, 95% CI: 1.3, 4.4). Adjusting for markers of pregnancy hemodynamics (glomerular filtration rate and plasma albumin), to the extent that they accurately reflect underlying pregnancy physiology, did not materially affect associations. These results suggest that pregnancy hemodynamics may not confound associations with birth outcomes when PFAS are measured early in pregnancy.
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Poluentes Ambientais/sangue , Desenvolvimento Fetal/efeitos dos fármacos , Fluorocarbonos/sangue , Hemodinâmica/fisiologia , Exposição Materna/estatística & dados numéricos , Adulto , Ácidos Alcanossulfônicos/sangue , Peso ao Nascer/efeitos dos fármacos , Creatinina/sangue , Feminino , Idade Gestacional , Humanos , Massachusetts , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Albumina Sérica , Fatores SocioeconômicosRESUMO
BACKGROUND: Reduced fetal growth is associated with perinatal and later morbidity. Prenatal exposure to environmental pollutants is linked to reduced fetal growth at birth, but the impact of concomitant exposure to multiple pollutants is unclear. The purpose of this study was to examine interactions between early pregnancy exposure to cigarette smoke, traffic pollution, and select perfluoroalkyl substances (PFASs) on birth weight-for-gestational age (BW/GA). METHODS: Among 1597 Project Viva mother-infant pairs, we assessed maternal cigarette smoking by questionnaire, traffic pollution at residential address by black carbon land use regression model, and plasma concentration of select PFASs in early pregnancy. We calculated sex-specific BW/GA z-scores, an index of fetal growth, from national reference data. We fit covariate-adjusted multi-pollutant linear regression models and examined interactions between exposures, using a likelihood-ratio test to identify a best-fit model. RESULTS: Two hundred six (13%) mothers smoked during pregnancy. Mean [standard deviation (SD)] for black carbon was 0.8 (0.3) µg/m3, perfluorooctane sulfonate (PFOS) was 29.1 (16.5) ng/mL, and BW/GA z-score was 0.19 (0.96). In the best-fit model, BW/GA z-score was lower in infants of mothers exposed to greater black carbon [- 0.08 (95% CI: -0.15, - 0.01) per interquartile range (IQR)]. BW/GA z-score (95% CI) was also lower in infants of mothers who smoked [- 0.09 (- 0.23, 0.06)] or were exposed to greater PFOS [- 0.03 (- 0.07, 0.02) per IQR], although confidence intervals crossed the null. There were no interactions between exposures. In secondary analyses, instead of PFOS, we examined perfluorononanoate (PFNA) [mean (SD): 0.7 (0.4) ng/mL], a PFAS more closely linked to lower BW/GA in our cohort. The best-fit multi-pollutant model included positive two-way interactions between PFNA and both black carbon and smoking (p-interactions = 0.03). CONCLUSIONS: Concurrent prenatal exposures to maternal smoking, black carbon, and PFOS are additively associated with lower fetal growth, whereas PFNA may attenuate associations of smoking and black carbon with lower fetal growth. It is important to examine interactions between multiple exposures in relation to health outcomes, as effects may not always be additive and may shed light on biological pathways.
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Poluentes Ambientais/efeitos adversos , Desenvolvimento Fetal/efeitos dos fármacos , Fluorocarbonos/efeitos adversos , Exposição Materna/efeitos adversos , Fuligem/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto , Ácidos Alcanossulfônicos/efeitos adversos , Feminino , Humanos , Massachusetts , Gravidez , Estudos Prospectivos , Poluição Relacionada com o Tráfego/efeitos adversosRESUMO
OBJECTIVE: To assess whether adding liothyronine (LT3) to levothyroxine (LT4) monotherapy normalizes serum thyrotropin (TSH) and thyroxine (T4) concentrations in children with congenital hypothyroidism and central resistance to thyroid hormone. STUDY DESIGN: We retrospectively studied 12 patients with congenital hypothyroidism and central resistance to thyroid hormone (6 treated with LT3+LT4 combined therapy and 6 treated with LT4 monotherapy). In patients receiving combined therapy, we compared serum concentrations of TSH, T4, and triiodothyronine before and after addition of LT3. We used repeated measures analysis to compare thyroid function in participants receiving combined therapy vs monotherapy, while accounting for age and intrasubject correlation. RESULTS: In patients receiving combined therapy, the addition of LT3 was associated with normalization of mean TSH (9.2 vs 4.5 mIU/L, P = .002), a lower proportion of TSH values greater than 10 mIU/L (35% vs 8%, P = .03), and a decrease in mean serum T4 by 23 ± 9% (P < .001). Compared with patients receiving LT4 monotherapy, patients receiving combined therapy had lower mean TSH (8.5 ± 0.9 vs 4.3 ± 0.4, P < .001), lower odds of TSH elevation greater than 10 mIU/L (OR 0.20, 95% CI 0.10-0.41, P < .001), and lower odds of T4 elevation (OR 0.21, 95% CI 0.04-1.09, P = .06). LT3 treatment did not increase serum T3 levels significantly. CONCLUSION: The addition of LT3 to LT4 monotherapy facilitates normalization of both serum TSH and T4 in patients with congenital hypothyroidism and central resistance to thyroid hormone. Larger prospective studies are needed to confirm these findings and to determine the effect of combined therapy on neurodevelopmental outcomes.
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Hipotireoidismo Congênito/tratamento farmacológico , Terapia de Reposição Hormonal/métodos , Tiroxina/uso terapêutico , Tri-Iodotironina/uso terapêutico , Biomarcadores/sangue , Hipotireoidismo Congênito/sangue , Monitoramento de Medicamentos , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Recém-Nascido , Modelos Logísticos , Masculino , Estudos Retrospectivos , Tireotropina/sangue , Tiroxina/sangue , Resultado do TratamentoRESUMO
BACKGROUND: Rodent and human studies suggest an association between air pollution exposure and type 2 diabetes mellitus, but the extent to which air pollution is associated with gestational diabetes mellitus (GDM) is less clear. METHODS: We used the Massachusetts Registry of Vital Records to study primiparous women pregnant from 2003-2008 without pre-existing diabetes. We used satellite-based spatiotemporal models to estimate first and second trimester residential particulate (PM2.5) exposure and geographic information systems to estimate neighborhood traffic density. We obtained GDM status from birth records. We performed logistic regression analyses adjusted for sociodemographics on the full cohort and after stratification by maternal age and smoking habits. RESULTS: Of 159,373 women, 5,381 (3.4 %) developed GDM. Residential PM2.5 exposure ranged 1.3-19.3 µg/m(3) over the second trimester. None of the exposures were associated with GDM in the full cohort [e.g. OR 0.99 (95 % CI: 0.95, 1.03) for each interquartile range (IQR) increment in second trimester PM2.5]. There were also no consistent associations after stratification by smoking habits. When the cohort was stratified by maternal age, women less than 20 years had 1.36 higher odds of GDM (95 % CI: 1.08, 1.70) for each IQR increment in second trimester PM2.5 exposure. CONCLUSIONS: Although we found no evidence of an association between air pollution exposure and GDM among all women in our study, greater exposure to PM2.5 during the second trimester was associated with GDM in the youngest age stratum.
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Poluição do Ar/efeitos adversos , Diabetes Gestacional/epidemiologia , Exposição Materna/efeitos adversos , Adulto , Fatores Etários , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Estudos de Coortes , Feminino , Humanos , Massachusetts/epidemiologia , Material Particulado/efeitos adversos , Material Particulado/análise , Gravidez , Segundo Trimestre da Gravidez , Adulto JovemRESUMO
Background Few studies have examined sex-specific associations of maternal gestational glycemia with cord blood hormones, which might predict later health. Methods In 976 women without pre-existing diabetes in the Project Viva cohort, we used linear regression to examine associations of maternal gestational glycemia with cord hormone concentrations, adjusted for maternal characteristics and stratified by infant sex. Results A total of 6.1% of women had gestational diabetes mellitus (GDM), 8.8% isolated hyperglycemia, 3.2% gestational impaired glucose tolerance, and 81.9% were normoglycemic. In boys, compared with infants of normoglycemic mothers, infants of GDM mothers had higher cord levels of IGF-2 (ß 35.55 ng/mL; 95% CI: 2.60, 68.50), IGFBP-3 (111.2 ng/mL; 5.53, 216.8), insulin (4.66 uU/mL; 2.38, 6.95), C-peptide (0.46 ng/mL; 0.25, 0.67), and leptin (3.51 ng/mL; 1.37, 5.64), but lower IGF-1 (-6.71 ng/mL; -12.7, - 0.76, adjusted for IGFBP-3). In girls, GDM offspring had higher cord blood levels of IGF-1 adjusted for IGFBP-3 (12.45 ng/mL; 4.85, 20.04). Boys, but not girls, of mothers with abnormal glucose tolerance but not GDM also had higher levels of some hormones. Conclusion GDM was associated with growth factors and adipokines in cord blood from boys, but only IGF-1 in girls. These findings suggest sex differences in responses to fetal overnutrition.
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Glicemia/metabolismo , Diabetes Gestacional/sangue , Sangue Fetal/metabolismo , Intolerância à Glucose/sangue , Hormônios Peptídicos/sangue , Adulto , Peptídeo C/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Leptina/sangue , Masculino , Parto , Gravidez , Estudos Prospectivos , Fatores SexuaisRESUMO
BACKGROUND: Prenatal air pollution exposure inhibits fetal growth, but implications for postnatal growth are unknown. METHODS: We assessed weights and lengths of US infants in the Project Viva cohort at birth and 6 months. We estimated 3rd-trimester residential air pollution exposures using spatiotemporal models. We estimated neighborhood traffic density and roadway proximity at birth address using geographic information systems. We performed linear and logistic regression adjusted for sociodemographic variables, fetal growth, and gestational age at birth. RESULTS: Mean birth weight-for-gestational age z-score (fetal growth) was 0.17 (standard deviation [SD] = 0.97; n = 2,114), 0- to 6-month weight-for-length gain was 0.23 z-units (SD = 1.11; n = 689), and 17% had weight-for-length ≥95th percentile at 6 months of age. Infants exposed to the highest (vs. lowest) quartile of neighborhood traffic density had lower fetal growth (-0.13 units [95% confidence interval (CI) = -0.25 to -0.01]), more rapid 0- to 6-month weight-for-length gain (0.25 units [95% CI = 0.01 to 0.49]), and higher odds of weight-for-length ≥95th percentile at 6 months (1.84 [95% CI = 1.11 to 3.05]). Neighborhood traffic density was additionally associated with an infant being in both the lowest quartile of fetal growth and the highest quartile of 0- to 6-month weight-for-length gain (Q4 vs. Q1, odds ratio = 3.01 [95% CI = 1.08 to 8.44]). Roadway proximity and 3rd-trimester black carbon exposure were similarly associated with growth outcomes. For 3rd-trimester particulate matter (PM2.5), effect estimates were in the same direction, but smaller and imprecise. CONCLUSIONS: Infants exposed to higher traffic-related pollution in early life may exhibit more rapid postnatal weight gain in addition to reduced fetal growth.
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Poluição do Ar/estatística & dados numéricos , Retardo do Crescimento Fetal/epidemiologia , Exposição Materna/estatística & dados numéricos , Material Particulado , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Aumento de Peso , Peso ao Nascer , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Obesidade Infantil/epidemiologia , Gravidez , Terceiro Trimestre da Gravidez , Análise Espaço-Temporal , Estados Unidos/epidemiologia , Emissões de VeículosRESUMO
Background: Triclosan is an endocrine-disrupting chemical, but associations with pubertal outcomes remain unclear. We examined associations of gestational and childhood triclosan with adolescent hormone concentrations and pubertal stage. Methods: We quantified urinary triclosan concentrations twice during pregnancy and seven times between birth and 12 years in participants recruited from Cincinnati, OH (2003-2006). We averaged concentrations across pregnancy and childhood and separately considered individual exposure periods in multiple informant models. At 12 years, we measured serum hormone concentrations (males [n = 72] and females [n = 84]-dehydroepiandrosterone-sulfate, luteinizing hormone, follicle-stimulating hormone; males-testosterone; females-estradiol). Also at age 12 years, participants self-reported physical development and menarchal timing. We estimated associations (95% confidence interval) of triclosan with hormone concentrations, more advanced physical development, and age at menarche. Results: For females, each doubling of childhood triclosan was associated with 16% lower estradiol concentrations (-29%, 0%), with stronger associations for measures closer to adolescence. We found suggestive evidence that higher triclosan at any age was associated with ~10% (for gestational triclosan: -18%, -2%) lower follicle-stimulating hormone concentrations among males and early postnatal (1-3 years) triclosan was associated with 63% (5%, 96%) lower odds of advanced pubic hair development in females. In multiple informant models, each doubling of gestational triclosan concentrations was associated with 5% (0%, 9%) earlier age at menarche, equivalent to 5.5 months. Conclusion: Gestational and childhood triclosan concentrations were related to some pubertal outcomes including hormone concentrations and age at menarche. Our findings highlight the relevance of elucidating potential sex-specific and time-dependent actions of triclosan.
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BACKGROUND: Findings on the associations between prenatal PFAS exposures and offspring adiposity are inconsistent. Whether such associations may extend to adolescence is especially understudied. OBJECTIVES: We investigated associations of prenatal PFAS exposures with offspring adiposity and body composition at 16-20 years of age. METHODS: We studied 545 mother-child pairs in the prospective prebirth cohort Project Viva (Boston, Massachusetts). We measured six PFAS (PFOA, PFOS, PFNA, PFHxS, EtFOSAA, and MeFOSAA) in maternal early pregnancy (median age=9.6wk, range: 5.7-19.6 wk) plasma samples. At the late adolescence visit (median age=17.4 y, range: 15.9-20.0 y), we obtained anthropometric measures and assessed body composition using bioelectrical impedance analysis and dual-energy X-ray absorptiometry. We examined associations of individual PFAS with obesity [i.e., age- and sex-specific body mass index (BMI) ≥95th percentile] and adiposity and body composition using multivariable Poisson and linear regression models, respectively. We assessed PFAS mixture effects using Bayesian kernel machine regression (BKMR) and quantile g-computation. We used fractional-polynomial models to assess BMI trajectories (at 3-20 years of age) by prenatal PFAS levels. RESULTS: Thirteen percent (n=73) of the children had obesity in late adolescence. After multivariable adjustment, higher prenatal PFAS concentrations were associated with higher obesity risk [e.g., 1.59 (95% CI: 1.19, 2.12), 1.24 (95% CI: 0.98, 1.57), and 1.49 (95% CI: 1.11, 1.99) times the obesity risk per doubling of PFOS, PFOA, and PFNA, respectively]. BKMR showed an interaction between PFOA and PFOS, where the positive association between PFOS and obesity was stronger when PFOA levels were lower. Each quartile increment of the PFAS mixture was associated with 1.52 (95% CI: 1.03, 2.25) times the obesity risk and 0.52 (95% CI: -0.02, 1.06) kg/m2 higher BMI. Children with higher prenatal PFOS, EtFOSAA, and MeFOSAA concentrations had higher rates of BMI increase starting from 9-11 years of age. DISCUSSION: Prenatal PFAS exposures may have obesogenic effects into late adolescence. https://doi.org/10.1289/EHP12597.
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Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Masculino , Gravidez , Feminino , Adolescente , Humanos , Adiposidade , Estudos Prospectivos , Teorema de Bayes , Obesidade , Composição CorporalRESUMO
BACKGROUND: Some phthalates are still widely used in food packaging, toys, and personal care products, and links to adverse health have motivated substitution with replacement chemicals. Few studies have examined patterns and predictors of phthalate replacement biomarkers in children. OBJECTIVE: To examine associations of sociodemographic, dietary, and urine collection characteristics with urinary concentrations of biomarkers of select phthalates and their replacements in mid-childhood. METHODS: We studied 830 children ages 6-10 years in 2007-2010 in a Boston-area cohort. We quantified urinary metabolites and summed their concentrations to calculate biomarkers of the concentrations of ten parent phthalates/replacements. We used linear regression to examine mutually adjusted associations of each predictor with each phthalate biomarker. We used logistic regression to examine predictors of 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH) biomarker detectability. RESULTS: Predictor characteristics explained 25-48% of urinary biomarker variability. Di-2-ethylhexyl terephthalate (DEHTP) biomarker was higher in females (18.7% [95% CI: 0.7, 39.9]), children who consumed more meat and dairy, and samples collected from later years. DINCH biomarker was more detectable in females (odds ratio [OR] 2.1 [95% CI: 1.5, 3.0]) and samples from later years. SIGNIFICANCE: Populations of children with increased urinary concentrations of phthalate and replacement biomarkers can be targeted for future study of sources of exposure, and identifying dietary predictors of biomarkers will directly guide future interventions. IMPACT: Our study uses data from a large cohort that is one of the first to measure DINCH, DEHTP, and metabolites of di-isononyl phthalate and di-isodecyl phthalate. Additionally, we evaluate predictors during mid-childhood when biomarkers might be highest. As the use of replacement phthalates increases, our study is one of the first to examine biomarker patterns and predictors among children.
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Disruptores Endócrinos , Poluentes Ambientais , Ácidos Ftálicos , Feminino , Humanos , Criança , Ácidos Ftálicos/urina , Modelos Lineares , Biomarcadores/urina , Ácidos Dicarboxílicos , Disruptores Endócrinos/urina , Exposição Ambiental , Poluentes Ambientais/urinaRESUMO
BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) may disrupt mammary gland development and function; thereby inhibiting milk supply and breastfeeding duration. However, conclusions on the potential effects of PFAS and breastfeeding duration are limited by prior epidemiologic studies that inconsistently adjusted for past cumulative breastfeeding duration and by a lack of examination of the joint effects of PFAS mixtures. METHODS: In Project Viva, a longitudinal cohort that enrolled pregnant participants from 1999 to 2002 in the greater Boston, MA area, we studied 1079 women who ever attempted to lactate. We investigated associations of plasma concentrations of select PFAS in early pregnancy (mean: 10.1â¯weeks gestation) with breastfeeding termination by 9â¯months, after which women typically cite self-weaning as the reason for terminating breastfeeding. We used Cox regression for single-PFAS models and quantile g-computation for mixture models, adjusting for sociodemographics, prior breastfeeding duration, and weeks of gestation at the time of blood draw. RESULTS: We detected 6 PFAS [perfluorooctane sulfonate; perfluorooctanoate (PFOA); perfluorohexane sulfonate; perfluorononanoate; 2-(N-ethyl-perfluorooctane sulfonamido) acetate (EtFOSAA); 2-(N-methyl-perfluorooctane sulfonamide) acetate (MeFOSAA)] in >98â¯% of samples. Sixty percent of lactating women terminated breastfeeding by 9â¯months postpartum. Women with higher plasma concentrations of PFOA, EtFOSAA, and MeFOSAA had a greater hazard of terminating breastfeeding in the first 9â¯months postpartum [HR (95â¯% CI) per doubling concentration: 1.20 (1.04, 1.38) for PFOA; 1.10 (1.01, 1.20) for EtFOSAA; 1.18 (1.08, 1.30) for MeFOSAA]. In the quantile g-computation model, simultaneously increasing all PFAS in the mixture by one quartile was associated with 1.17 (95â¯% CI: 1.05, 1.31) greater hazard of terminating breastfeeding in the first 9â¯months. CONCLUSION: Our findings suggest that exposure to PFAS may be associated with reduced breastfeeding duration and draw further attention to environmental chemicals that may dysregulate human lactation.
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Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Gravidez , Humanos , Feminino , Aleitamento Materno , LactaçãoRESUMO
Background: Nonessential metals have endocrine disrupting properties, interfere with cellular processes, generate reactive oxygen and deplete antioxidants, while essential metals and vitamins act as antioxidants. The extent to which prenatal metals and vitamins are associated with cord blood hormones involved in maternal and fetal metabolic and growth processes is unknown. Methods: We measured six nonessential (arsenic, barium, cadmium, cesium, lead, mercury) and four essential (magnesium, manganese, selenium, zinc) metals and trace elements, and two vitamins (B12 and folate) in first trimester blood from participants in the longitudinal pre-birth Project Viva cohort, who were recruited between 1999-2002 in eastern Massachusetts. We measured adiponectin, C-peptide, IGF-1, IGF-2, IGFBP-3, insulin, and leptin concentrations in cord blood (~n=695). We used covariate-adjusted quantile g-computation for mixtures and linear regression for individual exposures to estimate associations with cord blood peptide hormones. Results: The essential metal mixture (magnesium, manganese, selenium, zinc) was associated with higher IGF-1 (ß=3.20 ng/ml per quartile, 95% CI: 0.39, 6.01), IGF-2 (ß=10.93 ng/ml, 95% CI: 0.08, 21.79), and leptin (ß=1.03 ng/ml, 95% CI: 0.25, 1.80). Magnesium was associated with higher leptin (ß=2.90 ng/ml, 95% CI: 0.89, 4.91), while B12 was associated with lower adiponectin, IGF-2, and leptin, but higher C-peptide. Other individual nonessential metals were associated with cord blood hormones. Conclusions: Our findings suggest that some prenatal metals and vitamins are associated with cord blood hormones, which may influence growth and development.
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BACKGROUND: Gestational per- and polyfluoroalkyl substances (PFAS) exposure may be associated with adiposity and increased risk of obesity among children and adolescents. However, results from epidemiological studies evaluating these associations are inconsistent. OBJECTIVES: We estimated the associations of pregnancy PFAS concentrations with child body mass index (BMI) z-scores and risk of overweight/obesity in eight U.S. cohorts. METHODS: We used data from 1,391 mother-child pairs who enrolled in eight Environmental influences on Child Health Outcomes (ECHO) cohorts (enrolled: 1999-2019). We quantified concentrations of seven PFAS in maternal plasma or serum in pregnancy. We measured child weight and height between the ages of 2 and 5 y and calculated age- and sex-specific BMI z-scores; 19.6% children had more than one BMI measurement. We estimated covariate-adjusted associations of individual PFAS and their mixture with child BMI z-scores and risk of overweight/obesity using linear mixed models, modified Poisson regression models, and Bayesian approaches for mixtures. We explored whether child sex modified these associations. RESULTS: We observed a pattern of subtle positive associations of PFAS concentrations in pregnancy with BMI z-scores and risk of overweight/obesity. For instance, each doubling in perfluorohexane sulfonic acid concentrations was associated with higher BMI z-scores (ß=0.07; 95% CI: 0.01, 0.12). Each doubling in perfluroundecanoic acid [relative risk (RR)=1.10; 95% CI: 1.04, 1.16] and N-methyl perfluorooctane sulfonamido acetic acid (RR=1.06; 95% CI: 1.00, 1.12) was associated with increased risk of overweight/obesity, with some evidence of a monotonic dose-response relation. We observed weaker and more imprecise associations of the PFAS mixture with BMI or risk of overweight/obesity. Associations did not differ by child sex. DISCUSSION: In eight U.S.-based prospective cohorts, gestational exposure to higher levels of PFAS were associated with slightly higher childhood BMI z-score and risk of overweight or obesity. Future studies should examine associations of gestational exposure to PFAS with adiposity and related cardiometabolic consequences in older children. https://doi.org/10.1289/EHP11545.
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Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Masculino , Gravidez , Feminino , Adolescente , Humanos , Pré-Escolar , Criança , Índice de Massa Corporal , Sobrepeso/epidemiologia , Sobrepeso/induzido quimicamente , Sobrepeso/complicações , Estudos Prospectivos , Teorema de Bayes , Obesidade/induzido quimicamenteRESUMO
CONTEXT: Per- and polyfluoroalkyl substances (PFAS) and phthalates are 2 families of environmental endocrine disruptors that may be associated with areal lower bone mineral density (aBMD). OBJECTIVE: To examine associations between serum PFAS and urinary phthalate biomarker concentrations and their mixtures with aBMD Z-scores in adolescents. DESIGN, PATIENTS, AND MEASURES: We examined serial cross-sectional data from male (nâ =â 453) and female (nâ =â 395) 12- to 19-year-old participants in the 2011 through 2016 National Health and Nutrition Examination Survey with measures of serum PFAS, urinary phthalate metabolites, and dual-energy X-ray absorptiometry aBMD Z-scores (total body less head). In sex-specific models, we used linear regression to examine associations of individual PFAS and phthalate biomarkers with aBMD Z-scores, and Bayesian kernel machine regression to examine the association of the overall PFAS/phthalate biomarker mixture with aBMD Z-scores. We replicated the analysis, stratifying by race/ethnicity. RESULTS: Participants were (meanâ ±â SD) 15â ±â 2.1 years of age. In males, each doubling of serum perfluorooctanoate (PFOA), perfluorooctane sulfonate, urinary mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate, and the overall PFAS/phthalate mixture was associated with a lower aBMD Z-score (eg, for PFOA: -0.24; 95% CI, -0.41 to -0.06). Serum PFOA and urinary MiBP were associated with higher aBMD Z-scores in females (eg, for PFOA: 0.09; 95% CI, -0.07 to 0.25). Findings did not differ by race/ethnicity. CONCLUSIONS: Certain PFAS and phthalates may be associated with reduced bone mineral density in adolescent males. Bone mineral density tracks across the life course, so if replicated in longitudinal cohorts, this finding may have implications for lifelong skeletal health.
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Poluentes Ambientais , Fluorocarbonos , Adolescente , Adulto , Teorema de Bayes , Biomarcadores , Densidade Óssea , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos Nutricionais , Ácidos Ftálicos , Adulto JovemRESUMO
BACKGROUND: Hypertensive disorders of pregnancy (HDP), defined here as hypertensive disorders with onset in pregnancy (i.e., gestational hypertension, preeclampsia, and preeclampsia superimposed on chronic hypertension), affect up to 10% of pregnancies in the United States and are associated with substantial maternal and neonatal morbidity and mortality. Per- and polyfluoroalkyl substances (PFAS) are associated with adverse cardiometabolic outcomes during pregnancy, but associations between PFAS and HDP are inconsistent and joint effects of PFAS mixtures have not been evaluated. METHODS: We studied 1,558 pregnant individuals from the Project Viva cohort, recruited during 1999-2002. We quantified concentrations of eight PFAS in plasma samples (median 9.7 weeks of gestation). Using clinical records, we calculated trimester-specific mean systolic (SBP) and diastolic (DBP) blood pressure and categorized HDP status [no HDP (normotensive & chronic hypertension), gestational hypertension, preeclampsia]. We estimated associations of individual PFAS with HDP using multinomial logistic regression and estimated associations with blood pressure using linear regression. We used Bayesian kernel machine regression (BKMR) and quantile g-computation to assess joint effects of the PFAS mixture on HDP and blood pressure measures. RESULTS: Four percent of participants developed preeclampsia and 7% developed gestational hypertension. We observed higher odds of gestational hypertension, but not preeclampsia, per doubling of perfluorooctanoate (PFOA) [OR = 1.51 (95% confidence interval: 1.12, 2.03)], perfluorooctane sulfonate (PFOS) [OR = 1.38 (1.04, 1.82)], and perfluorohexane sulfonate [OR = 1.28 (1.06, 1.54)] concentrations. We observed higher mean DBP per doubling of PFOA [2nd trimester (T2): 0.39 mmHg (-0.01, 0.78); 3rd trimester (T3): 0.56 mmHg (0.14, 0.98)] and PFOS [T2: 0.46 mmHg (0.11, 0.82); T3: 0.43 mmHg (0.05, 0.80)]. The PFAS mixture was positively associated with odds of gestational hypertension [75th vs. 50th percentile: OR = 1.14 (95% credible interval:1.03, 1.25), BKMR] and mean DBP [T2 = 0.17 mmHg (-0.06, 0.40); T3 = 0.22 mmHg (-0.03, 0.48), BKMR]. CONCLUSIONS: These findings suggest that exposure to certain PFAS may increase the odds of gestational hypertension during pregnancy, with potential implications for subsequent maternal and child health outcomes.