Michal Brazda
@comtesfht.cz
COMTES FHT
Scopus Publications
Scopus Publications
Caitlin G. Howe, Birgit Claus Henn, Shohreh F. Farzan, Rima Habre, Sandrah P. Eckel, Brendan H. Grubbs, Thomas A. Chavez, Dema Faham, Laila Al-Marayati, Deborah Lerner,et al.
Elsevier BV
Dana Boyd Barr, Kurunthachalam Kannan, Yuxia Cui, Lori Merrill, Lauren M. Petrick, John D. Meeker, Timothy R. Fennell, and Elaine M. Faustman
Elsevier BV
Pahriya Ashrap, Amira Aker, Deborah J. Watkins, Bhramar Mukherjee, Zaira Rosario-Pabón, Carmen M. Vélez-Vega, Akram Alshawabkeh, José F. Cordero, and John D. Meeker
Elsevier BV
Zorimar Rivera-Núñez, Pahriya Ashrap, Emily S. Barrett, Deborah J. Watkins, Amber L. Cathey, Carmen M. Vélez-Vega, Zaira Rosario, José F. Cordero, Akram Alshawabkeh, and John D. Meeker
Elsevier BV
Pahriya Ashrap, Deborah J. Watkins, Ginger L. Milne, Kelly K. Ferguson, Rita Loch-Caruso, Jennifer Fernandez, Zaira Rosario, Carmen M. Vélez-Vega, Akram Alshawabkeh, José F. Cordero,et al.
MDPI AG
Metal exposure has been associated with a wide range of adverse birth outcomes and oxidative stress is a leading hypothesis of the mechanism of action of metal toxicity. We assessed the relationship between maternal exposure to essential and non-essential metals and metalloids in pregnancy and oxidative stress markers, and sought to identify windows of vulnerability and effect modification by fetal sex. In our analysis of 215 women from the PROTECT birth cohort study, we measured 14 essential and non-essential metals in urine samples at three time points during pregnancy. The oxidative stress marker 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite 2,3-dinor-5,6-dihydro-15-15-F2t-IsoP, as well as prostaglandin F2α (PGF2α), were also measured in the same urine samples. Using linear mixed models, we examined the main effects of metals on markers of oxidative stress as well as the visit-specific and fetal sex-specific effects. After adjustment for covariates, we found that a few urinary metal concentrations, most notably cesium (Cs) and copper (Cu), were associated with higher 8-iso-PGF2α with effect estimates ranging from 7.3 to 14.9% for each interquartile range, increase in the metal concentration. The effect estimates were generally in the same direction at the three visits and a few were significant only among women carrying a male fetus. Our data show that higher urinary metal concentrations were associated with elevated biomarkers of oxidative stress. Our results also indicate a potential vulnerability of women carrying a male fetus.
Max T. Aung, Amira M. Aker, and John D. Meeker
Royal Society of Chemistry
Mary E. Ingle, Lidia Mínguez-Alarcón, Courtney C. Carignan, Heather M. Stapleton, Paige L. Williams, Jennifer B. Ford, Molly B. Moravek, Marie S. O'Neill, Lu Wang, Russ Hauser,et al.
Elsevier BV
Amber L. Cathey, Deborah J. Watkins, Zaira Y. Rosario, Carmen M. Vélez Vega, Rita Loch-Caruso, Akram N. Alshawabkeh, José F. Cordero, and John D. Meeker
Elsevier BV
Pahriya Ashrap, John D. Meeker, Brisa N. Sánchez, Niladri Basu, Marcela Tamayo-Ortiz, Maritsa Solano-González, Adriana Mercado-García, Martha M. Téllez-Rojo, Karen E. Peterson, and Deborah J. Watkins
Springer Science and Business Media LLC
AbstractBackgroundEndocrine disrupting chemicals (EDCs) such as metals have been reported to alter circulating reproductive hormone concentrations and pubertal development in animals. However, the relationship has rarely been investigated among humans, with the exception of heavy metals, such as Pb and Cd. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone concentrations and sexual maturation and progression among boys from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts.MethodsOur analysis included 118 pregnant women and their male children from the ELEMENT study. Essential and non-essential metals were measured in urine collected from the mothers during the third trimester of pregnancy and their male children at 8–14 years. Reproductive hormone concentrations [serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG)] were measured in blood samples from the children at 8–14 years. We also assessed Tanner stages for sexual maturation (genital, pubic hair development, and testicular volume), at two time points (8–14, 10–18 years). We used linear regression to independently examine urinary metal concentrations in relation to each peripubertal reproductive hormones adjusting for child age and BMI. Generalized estimation equations (GEEs) were used to evaluate the association of in utero and peripubertal metal exposures with sexual maturation and progression during follow-up based on Tanner staging and testicular volume.ResultsIn utero and prepubertal concentrations of some urinary metals were associated with increased concentrations of peripubertal reproductive hormones, especially non-essential metal(loid)s As and Cd (in utero), and Ba (peripubertal) as well as essential metal Mo (in utero) in association with testosterone. More advanced pubic hair developmental stage and higher testicular volume at the early teen visit was observed for boys with higher non-essential metal concentrations, including in utero Al and peripubertal Ba, and essential metal Zn concentration (peripubertal). These metals were also associated with slower pubertal progression between the two visits.ConclusionThese findings suggest that male reproductive development may be associated with both essential and non-essential metal exposure during in utero and peripubertal windows.
Max T. Aung, Yanyi Song, Kelly K. Ferguson, David E. Cantonwine, Lixia Zeng, Thomas F. McElrath, Subramaniam Pennathur, John D. Meeker, and Bhramar Mukherjee
Springer Science and Business Media LLC
Abstract Diverse toxicological mechanisms may mediate the impact of environmental toxicants (phthalates, phenols, polycyclic aromatic hydrocarbons, and metals) on pregnancy outcomes. In this study, we introduce an analytical framework for multivariate mediation analysis to identify mediation pathways (q = 61 mediators) in the relationship between environmental toxicants (p = 38 analytes) and gestational age at delivery. Our analytical framework includes: (1) conducting pairwise mediation for unique exposure-mediator combinations, (2) exposure dimension reduction by estimating environmental risk scores, and (3) multivariate mediator analysis using either Bayesian shrinkage mediation analysis, population value decomposition, or mediation pathway penalization. Dimension reduction demonstrates that a one-unit increase in phthalate risk score is associated with a total effect of 1.07 lower gestational age (in weeks) at delivery (95% confidence interval: 0.48–1.67) and eicosanoids from the cytochrome p450 pathway mediated 26% of this effect (95% confidence interval: 4–63%). Eicosanoid products derived from the cytochrome p450 pathway may be important mediators of phthalate toxicity.
Wei Perng, Nicole M. Kasper, Deborah J. Watkins, Brisa N. Sanchez, John D. Meeker, Alejandra Cantoral, Maritsa Solano-González, Martha Maria Tellez-Rojo, and Karen Peterson
Mary Ann Liebert Inc
Background: The postpartum period may be a vulnerable life stage for a woman's cardiometabolic health. We examined associations of exposure to common endocrine-disrupting chemicals (EDCs) during pregnancy with weight from delivery through 1 year postpartum among 199 women in Mexico City. Materials and Methods: During each trimester of pregnancy, we collected a urine sample to assay bisphenol A (BPA), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-3-carboxypropyl phthalate (MCPP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and monoethyl phthalate (MEP). We calculated summary scores for di-2-ethylhexyl phthalate metabolites (ΣDEHP) and dibutyl phthalate metabolites (ΣDBP). We calculated the geometric mean of each EDC across pregnancy for use in the analysis. At delivery and three additional times during the first year postpartum, we measured the women's weight. We used mixed-effects linear regression models to estimate associations of each EDC with weight at delivery (kg) and weight change (kg/year) from delivery through 1 year postpartum. Covariates included urinary specific gravity, maternal age, parity, height, first trimester body mass index, and gestational age at enrollment. Results: Mean ± standard deviation weight change during the first postpartum year was -0.49 ± 4.04 kg. The EDCs were inversely associated with weight at delivery, but positively associated with weight change through 1 year postpartum. For example, each interquartile range of urinary ΣDEHP corresponded with 1.38 (95% confidence interval: 0.44-2.33) kg lower weight at delivery and 1.01 (0.41--1.61) kg/year slower rate of weight loss. We observed similar associations for other EDCs. Conclusions: Prenatal exposure to EDCs is associated with lower weight at delivery, but slower rate of weight loss through the first postpartum year.
Libni A. Torres-Olascoaga, Deborah Watkins, Lourdes Schnaas, John D. Meeker, Maritsa Solano-Gonzalez, Erika Osorio-Valencia, Karen E. Peterson, Martha María Tellez-Rojo, and Marcela Tamayo-Ortiz
MDPI AG
In utero phthalate exposure has been associated with neurodevelopmental disorders, nevertheless, trimester-specific susceptibility remains understudied. Our aim was to identify susceptible windows to the effects of gestational High-Molecular-Weight Phthalates (HMWP) exposure on 48 months’ neurodevelopment. We measured six HMWP metabolites (MEHP, MEHHP, MEOHP, MECPP, MBzP and MCPP) in urine samples collected during each trimester from women in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohort (n = 218). We assessed children’s motor (MS), cognitive (GCI) and memory (MeS) abilities using McCarthy Scales of Children’s Abilities (MSCA). We used linear regression models to examine associations between trimester-specific phthalate metabolites and MSCA scores, adjusted for sex, gestational age, breastfeeding, and maternal IQ. Although phthalate concentrations were similar across trimesters, first and second trimester phthalates were inversely associated with MS and GCI, with first trimester associations with MS being the strongest and statistically significant. Stronger associations were seen with MS and GCI among boys compared to girls, however interaction terms were not statistically significant. Our results suggest that early gestation is a sensitive window of exposure to HMWP for neurodevelopment, particularly in boys. Regulations on phthalate content in food as well as pregnancy consumption guidelines are necessary to protect future generations.
Caitlin G. Howe, Birgit Claus Henn, Sandrah P. Eckel, Shohreh F. Farzan, Brendan H. Grubbs, Thomas A. Chavez, Tahlia L. Hodes, Dema Faham, Laila Al-Marayati, Deborah Lerner,et al.
Environmental Health Perspectives
Background: Reduced fetal growth increases the risk for adverse health outcomes. Growing evidence suggests that metal exposures contribute to reduced fetal growth, but little is known about the effects of complex metal mixtures. Objectives: We investigated the impact of a complex mixture of metals on birth weight for gestational age (BW for GA) in the Maternal and Developmental Risks from Environmental and Social Stressors study, a predominately lower-income Hispanic pregnancy cohort in Los Angeles, California. Methods: Cadmium (Cd), cobalt (Co), mercury (Hg), nickel (Ni), molybdenum (Mo), lead (Pb), antimony (Sb), tin (Sn), and thallium (Tl) were measured by inductively coupled plasma mass spectrometry (ICP-MS) in maternal urine samples collected in early pregnancy (median GA: 13.1 wk). Speciated urinary arsenic (As) (inorganic+monomethyl+dimethyl As) was measured by high-performance liquid chromatography coupled to ICP-MS. Primary analyses focused on a mixture of seven metals that have previously been associated individually with fetal growth (i.e., As, Cd, Co, Hg, Ni, Pb, Tl) (n=262). In exploratory analyses, we additionally examined three metals that have been less studied in relation to fetal growth (i.e., Mo, Sb, Sn). Covariate-adjusted Bayesian kernel machine regression was used to investigate metal mixture associations with BW for GA z-scores. Results: In primary analyses, Hg and Ni ranked highest as predictors of BW for GA. An inverse linear association was estimated for Hg, whereas a positive association was estimated for Ni at low-to-moderate concentrations. A potential interaction between Hg and Ni was also identified. In our exploratory analysis, Sb ranked highest as a predictor of BW for GA, followed by Hg and Ni. Conclusions: Our findings suggest that in this understudied population, Hg may reduce fetal growth, whereas Ni may promote fetal growth. We also identified Sb as a potential metal of concern for this population, which merits additional investigation. https://doi.org/10.1289/EHP7201
Mary E. Ingle, Lidia Mínguez-Alarcón, Ryan C. Lewis, Paige L. Williams, Jennifer B. Ford, Ramace Dadd, Russ Hauser, and John D. Meeker
Elsevier BV
Deborah J. Watkins, Héctor Ramón Torres Zayas, Carmen M. Vélez Vega, Zaira Rosario, Michael Welton, Luis D. Agosto Arroyo, Nancy Cardona, Zulmarie J. Díaz Reguero, Amailie Santos Rivera, Gredia Huerta-Montañez,et al.
Springer Science and Business Media LLC
Prior to Hurricane Maria, Puerto Rico already had 200+ hazardous waste sites, significant contamination of water resources, and among the highest rates of preterm birth in the USA. To address these issues, the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) Center was formed in 2010 to investigate prenatal environmental exposures, particularly phthalates, and adverse birth outcomes. Recent work from the PROTECT study confirms that in utero exposure to certain phthalates is associated with shorter gestation and increased risk of preterm birth. However, previous research also suggests that pregnant women who experience a natural disaster such as Hurricane Maria are at higher risk of adverse birth outcomes, but it is unknown whether this is due to stress, hazardous exposures, or a combination of factors. Thus, the aim of this analysis was to characterize hurricane-related changes in phthalate exposures and experiences within the PROTECT cohort. Among 176 participants who were pregnant during or within 5 months after Maria, 122 completed a questionnaire on hurricane-related experiences. Questionnaire results and biomarkers of exposure suggest that participants did not have regular access to fresh foods and water during hurricane recovery, and almost half reported structural damage to their home. In addition, biomarker concentrations of phthalates commonly used in food packaging were higher among participants post-hurricane, while phthalates commonly used in personal care products were lower compared to pre-hurricane levels. Hurricane-related increases in phthalate exposure, as well as widespread structural damage, food and water shortages, and long-term absence of electricity and cell phone service, likely increased the risk of adverse birth outcomes among this already vulnerable population.
Justin Manjourides, Emily Zimmerman, Deborah J Watkins, Thomas Carpenito, Carmen M Vélez-Vega, Gredia Huerta-Montañez, Zaira Rosario, Ishwara Ayala, Carlos Vergara, Zlatan Feric,et al.
BMJ
PurposePuerto Rican children experience high rates of asthma and obesity. Further, infants born in Puerto Rico are more at risk for being born prematurely compared with infants on the mainland USA. Environmental exposures from multiple sources during critical periods of child development, potentially modified by psychosocial factors, may contribute to these adverse health outcomes. To date, most studies investigating the health effects of environmental factors on infant and child health have focused on single or individual exposures.ParticipantsInfants currently in gestation whose mother is enrolled in Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort, and infants and children already born to mothers who participated in the PROTECT study.Findings to dateData collection and processing remains ongoing. Demographic data have been collected on 437 mother–child pairs. Birth outcomes are available for 420 infants, neurodevelopmental outcomes have been collected on 319 children. Concentrations of parabens and phenols in maternal spot urine samples have been measured from 386 mothers. Center for Research on Early Childhood Exposure and Development mothers have significantly higher urinary concentrations of dichlorophenols, triclosan and triclocarban, but lower levels of several parabens compared with reference values from a similar population drawn from the National Health and Nutrition Examination Survey.Future plansData will continue to be collected through recruitment of new births with a target of 600 children. Seven scheduled follow-up visits with existing and new participants are planned. Further, our research team continues to work with healthcare providers, paediatricians and early intervention providers to support parent’s ability to access early intervention services for participants.
Irene Souter, Andrea Bellavia, Paige L. Williams, T.I.M. Korevaar, John D. Meeker, Joseph M. Braun, Ralph A. de Poortere, Maarten A. Broeren, Jennifer B. Ford, Antonia M. Calafat,et al.
Environmental Health Perspectives
Background: Although previous epidemiological studies have explored associations of phthalate metabolites with thyroid function, no studies to date have assessed associations of mixtures with thyroid function and autoimmunity among potentially susceptible subgroups such as subfertile women. Objective: We aimed to explore associations of mixtures of urinary phthalate metabolites with serum markers of thyroid function and autoimmunity. Methods: This cross-sectional study included 558 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2005–2015). We quantified urinary concentrations of eight phthalate metabolites using mass spectrometry, and biomarkers of thyroid function [thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, TT4) and triiodothyronine (fT3, TT3), and autoimmunity [thyroid peroxidase and thyroglobulin antibodies (TPOAb and TgAb, respectively)] in serum using electrochemiluminescence assays. We applied principal component analysis (PCA) and Bayesian kernel machine regression (BKMR) to identify the main patterns of urinary phthalate metabolites. We used linear mixed models to assess the association between PCA-derived factor scores in quintiles and serum thyroid function and autoimmunity, adjusting for age, body mass index (BMI), specific gravity (SG), and, for the PCA, other factor scores. Results: We observed two factors using PCA, one representing the di(2-ethylhexyl) (DEHP) and another non-DEHP metabolites. Compared to women in the lowest quintile of the DEHP factor scores, women in the highest quintile had significantly lower serum concentrations of fT4, TT4, fT3, and TT3 [absolute difference: −0.62; 95% confidence interval (CI): −0.12, −0.01; p=0.04; absolute difference: −8.31; 95% CI: −13.8, −2.85; p=0.003; absolute difference: −0.37; 95% CI: 0.54, −0.19; p<0.0001; and absolute difference: −0.21; 95% CI: −0.32, −0.10; p=0.003, respectively]. Using BKMR, we observed that mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was the primary contributor to these negative associations. DEHP and non-DEHP factor scores were not associated with serum TSH, TgAb, or TPOAb. Conclusions: Mixtures of urinary DEHP metabolites were inversely associated with serum biomarkers of thyroid function but not with autoimmunity, which were within normal ranges for healthy adult women. https://doi.org/10.1289/EHP6740
Mary E Ingle, Lidia Mínguez-Alarcón, Courtney C Carignan, Heather M Stapleton, Paige L Williams, Jennifer B Ford, Molly B Moravek, Russ Hauser, John D Meeker, and
Oxford University Press (OUP)
Abstract STUDY QUESTION Are serum concentrations of polybrominated diphenyl ethers (PBDEs) and hydroxylated brominated diphenyl ethers (OH-BDEs) associated with IVF endpoints? SUMMARY ANSWER Positive associations were observed for BDE153 and several OH-BDEs with IVF endpoints. WHAT IS KNOWN ALREADY PBDEs have been voluntarily phased out of production in the USA and EU due to their persistence and toxicity to humans and ecosystems. PBDEs have been associated with implantation failure among women undergoing IVF, yet some animal studies suggest greater toxicity from their metabolites, OH-BDEs. STUDY DESIGN, SIZE, DURATION We evaluated a subset of 215 women (contributing 330 IVF cycles) enrolled between 2005 and 2016 in a longitudinal cohort based at Massachusetts General Hospital Fertility Center. PARTICIPANTS/MATERIALS, SETTING, METHODS The following PBDEs were quantified: 47, 99, 100, 153 and 154 and the following OH-BDEs: 3-OH-BDE47, 5-OH-BDE47, 6-OH-BDE47 and 4-OH-BDE49. Clinical endpoints of IVF treatments were abstracted from electronic medical records. Associations of log-transformed PBDEs and OH-BDEs with IVF outcomes were assessed using multivariable generalized mixed models and cluster weighted generalized estimating equation models adjusted for lipids, age, BMI, race, year of sample collection, IVF protocol and FSH levels. Outcomes were adjusted to represent a percent change in outcome with an increase equal to the magnitude of the difference between the 75th and 25th percentiles for each specific compound (interquartile range (IQR) increase). MAIN RESULTS AND THE ROLE OF CHANCE Detection frequencies were highest for congeners 47 and 153 (82% ≥ method detection limit (MDL)) and metabolites 3 and 5-OH-BDE47 and 4-OH-BDE49 (92% &gt; MDL). PBDE and OH-BDE geometric mean concentrations declined by up to 80% between participants recruited in 2005 and those recruited in 2016. An IQR increase of BDE153 was associated with an increase in the probability of implantation (relative risk (RR) = 1.26, 95% CI: 1.16, 1.36), clinical pregnancy (RR = 1.32, 95% CI: 1.19, 1.46) and live birth (RR = 1.34; 95% CI: 1.15, 1.54). An IQR increase in 3 and 5-OH-BDE47 was associated with increased probabilities of implantation (RR = 1.52; 95% CI: 1.11, 2.09), clinical pregnancy (RR = 1.66; 95% CI: 1.17, 2.36), and live birth (RR = 1.61; 95% CI: 1.07, 2.40). When models were stratified by race (White (86%)/Other race (14%)), associations remained positive for White women, yet inverse associations were observed for Other race women. An IQR increase in BDE47 was associated with a 46% decreased probability of clinical pregnancy (95% CI: 0.31, 0.95) for Other race women. LIMITATIONS, REASONS FOR CAUTION Despite the long half-lives of PBDEs and OH-BDEs, exposure misclassification is possible for women who underwent multiple treatment cycles over several months or years. It is also possible another medium, such as follicular fluid would be optimal to characterize exposure. We also tested associations for multiple congeners and metabolites with multiple outcomes. WIDER IMPLICATIONS OF THE FINDINGS Detections of serum concentrations of PBDEs and OH-BDEs were highest in the early years of the study and suggests that the phase-out of these compounds has contributed to a decrease in exposure. The negative associations found for PBDEs and IVF outcomes among other race women suggests the potential for racial disparity. Potential racial disparities in PBDE exposure and exploration of alternative flame retardants with reproductive health outcomes should be the focus of future investigations. STUDY FUNDING/COMPETING INTEREST(S) Funding for this research was supported by the National Institutes of Environmental Health Sciences (NIEHS) [R01 ES009718, ES022955, ES000002 and 009718T32ES007069]. The authors have no conflicts of interest.
Pahriya Ashrap, Deborah J. Watkins, Bhramar Mukherjee, Jonathan Boss, Michael J. Richards, Zaira Rosario, Carmen M. Vélez-Vega, Akram Alshawabkeh, José F. Cordero, and John D. Meeker
Elsevier BV
Sean M. Harris, Yuan Jin, Rita Loch-Caruso, Ingrid Y. Padilla, John D. Meeker, and Kelly M. Bakulski
Elsevier BV
Pahriya Ashrap, Deborah J. Watkins, Bhramar Mukherjee, Jonathan Boss, Michael J. Richards, Zaira Rosario, Carmen M. Vélez-Vega, Akram Alshawabkeh, José F. Cordero, and John D. Meeker
Elsevier BV
Max T. Aung, John D. Meeker, Jonathan Boss, Kelly M. Bakulski, Bhramar Mukherjee, David E. Cantonwine, Thomas F. McElrath, and Kelly K. Ferguson
Elsevier BV
Amira Aker, Rafael E. Rios McConnell, Rita Loch-Caruso, Sung Kyun Park, Bhramar Mukherjee, Zaira Y. Rosario, Carmen M. Vélez-Vega, Gredia Huerta-Montanez, Akram N. Alshawabkeh, José F. Cordero,et al.
Elsevier BV
Amber Cathey, Deborah J. Watkins, Brisa N. Sánchez, Marcela Tamayo-Ortiz, Maritsa Solano-Gonzalez, Libni Torres-Olascoaga, Martha Maria Téllez-Rojo, Karen E. Peterson, and John D. Meeker
Elsevier BV
Mary E. Ingle, Deborah Watkins, Zaira Rosario, Carmen M. VélezVega, Antonia M. Calafat, Maria Ospina, Kelly K. Ferguson, José F Cordero, Akram Alshawabkeh, and John D. Meeker
Elsevier BV