Publications by authors named "José F Cordero"

81 Publications

Disparities in Risks of Inadequate and Excessive Intake of Micronutrients during Pregnancy.

J Nutr 2021 Sep 7. Epub 2021 Sep 7.

Department of Pediatrics, New York University Grossman School of Medicine, New York, NY, USA.

Background: Inadequate or excessive intake of micronutrients in pregnancy has potential to negatively impact maternal/offspring health outcomes.

Objective: The aim was to compare risks of inadequate or excessive micronutrient intake in diverse females with singleton pregnancies by strata of maternal age, race/ethnicity, education, and prepregnancy BMI.

Methods: Fifteen observational cohorts in the US Environmental influences on Child Health Outcomes (ECHO) Consortium assessed participant dietary intake with 24-h dietary recalls (n = 1910) or food-frequency questionnaires (n = 7891) from 1999-2019. We compared the distributions of usual intake of 19 micronutrients from food alone (15 cohorts; n = 9801) and food plus dietary supplements (10 cohorts with supplement data; n = 7082) to estimate the proportion with usual daily intakes below their age-specific daily Estimated Average Requirement (EAR), above their Adequate Intake (AI), and above their Tolerable Upper Intake Level (UL), overall and within sociodemographic and anthropometric subgroups.

Results: Risk of inadequate intake from food alone ranged from 0% to 87%, depending on the micronutrient and assessment methodology. When dietary supplements were included, some women were below the EAR for vitamin D (20-38%), vitamin E (17-22%), and magnesium (39-41%); some women were above the AI for vitamin K (63-75%), choline (7%), and potassium (37-53%); and some were above the UL for folic acid (32-51%), iron (39-40%), and zinc (19-20%). Highest risks for inadequate intakes were observed among participants with age 14-18 y (6 nutrients), non-White race or Hispanic ethnicity (10 nutrients), less than a high school education (9 nutrients), or obesity (9 nutrients).

Conclusions: Improved diet quality is needed for most pregnant females. Even with dietary supplement use, >20% of participants were at risk of inadequate intake of ≥1 micronutrients, especially in some population subgroups. Pregnancy may be a window of opportunity to address disparities in micronutrient intake that could contribute to intergenerational health inequalities.
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http://dx.doi.org/10.1093/jn/nxab273DOI Listing
September 2021

Preterm birth and PM in Puerto Rico: evidence from the PROTECT birth cohort.

Environ Health 2021 06 11;20(1):69. Epub 2021 Jun 11.

Department of Civil and Environmental Engineering, Tufts University, Anderson Hall, 200 College Avenue, Medford, MA, 02155, USA.

Background: Preterm birth (PTB, birth before 37 weeks of gestation) has been associated with adverse health outcomes across the lifespan. Evidence on the association between PTB and prenatal exposure to air pollutants is inconsistent, and is especially lacking for ethnic/racial minority populations.

Methods: We obtained data on maternal characteristics and behaviors and PTB and other birth outcomes for women participating in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort, who lived in municipalities located along the North Coast of Puerto Rico. We assessed pre-natal PM exposures for each infant based on the nearest US Environmental Protection Agency monitor. We estimated prenatal phthalate exposures as the geometric mean of urinary measurements obtained during pregnancy. We then examined the association between PM and PTB using modified Poisson regression and assessed modification of the association by phthalate exposure levels and sociodemographic factors such as maternal age and infant gender.

Results: Among 1092 singleton births, 9.1% of infants were born preterm and 92.9% of mothers had at least a high school education. Mothers had a mean (standard deviation) age of 26.9 (5.5) years and a median (range) of 2.0 (1.0-8.0) pregnancies. Nearly all women were Hispanic white, black, or mixed race. Median (range) prenatal PM concentrations were 6.0 (3.1-19.8) μ g/m. Median (interquartile range) prenatal phthalate levels were 14.9 (8.9-26.0) and 14.5 (8.4-26.0), respectively, for di-n-butyl phthalate (DBP) and di-isobutyl phthalate (DiBP). An interquartile range increase in PM was associated with a 1.2% (95% CI 0.4, 2.1%) higher risk of PTB. There was little difference in PTB risk in strata of infant sex, mother's age, family income, history of adverse birth outcome, parity, and pre-pregnancy body mass index. Pregnancy urinary phthalate metabolite levels did not modify the PM-PTB association.

Conclusion: Among ethnic minority women in Puerto Rico, prenatal PM exposure is associated with a small but significant increase in risk of PTB.
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http://dx.doi.org/10.1186/s12940-021-00748-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196435PMC
June 2021

Performance of urine, blood, and integrated metal biomarkers in relation to birth outcomes in a mixture setting.

Environ Res 2021 09 10;200:111435. Epub 2021 Jun 10.

University of Michigan School of Public Health, Department of Environmental Health Sciences, Ann Arbor, MI, United States. Electronic address:

Background: Studies on the health effects of metal mixtures typically utilize biomarkers measured in a single biological medium, such as blood or urine. However, the ability to evaluate mixture effects are limited by the uncertainty whether a unified medium can fully capture exposure for each metal. Therefore, it is important to compare and assess metal mixtures measured in different media in epidemiology studies.

Objectives: The aim of this study was to examine the mixture predictive performance of urine and blood metal biomarkers and integrated multi-media biomarkers in association with birth outcomes.

Methods: In our analysis of 847 women from the Puerto Rico PROTECT Cohort, we measured 10 essential and non-essential metals in repeated and paired samples of urine and blood during pregnancy. For each metal, we integrated exposure estimates from paired urine and blood biomarkers into multi-media biomarkers (MMBs), using intraclass-correlation coefficient (ICC) and weighted quantile sum (WQS) approaches. Using Ridge regressions, four separate Environmental risk scores (ERSs) for metals in urine, blood, MMB, and MMB were computed as a weighted sum of the 10 metal concentrations. We then examined associations between urine, blood, and multi-media biomarker ERSs and birth outcomes using linear and logistic regressions, adjusting for maternal age, maternal education, pre-pregnancy body mass index (BMI), and second-hand smoke exposure. The performance of each ERS was evaluated with continuous and tertile estimates and 95% confidence intervals of the odds ratio of preterm birth using area under the curve (AUC).

Results: Pb was the most important contributor of blood ERS as well as the two integrated multi-media biomarker ERSs. Individuals with high ERS (3rd tertile) showed increased odds of preterm birth compared to individuals with low ERS (1st tertile), with 2.8-fold (95% CI, 1.49 to 5.40) for urine (specific gravity corrected); 3.2- fold (95% CI, 1.68 to 6.25) for blood; 3.9-fold (95% CI, 1.72 to 8.66) for multi-media biomarkers composed using ICC; and 5.2-fold (95% CI, 2.34 to 11.42) for multi-media biomarkers composed using WQS. The four ERSs had comparable predictive performances (AUC ranging from 0.64 to 0.68) when urine is examined with specific gravity corrected concentrations.

Conclusions: Within a practical metal panel, measuring metals in either urine or blood may be an equally good approach to evaluate the metals as a mixture. Applications in practical study design require validation of these methods with other cohorts, larger panels of metals and within the context of other adverse health effects of interest.
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http://dx.doi.org/10.1016/j.envres.2021.111435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403638PMC
September 2021

Non-nutritive suck and airborne metal exposures among Puerto Rican infants.

Sci Total Environ 2021 Oct 26;789:148008. Epub 2021 May 26.

Department of Civil and Environmental Engineering, Tufts University, 200 College Ave, Medford, MA 02155, USA. Electronic address:

Air pollution has been shown to impact multiple measures of neurodevelopment in young children. Its effects on particularly vulnerable populations, such as ethnic minorities, however, is less studied. To address this gap in the literature, we assess the associations between infant non-nutritive suck (NNS), an early indicator of central nervous system integrity, and air pollution exposures in Puerto Rico. Among infants aged 0-3 months enrolled in the Center for Research on Early Childhood Exposure and Development (CRECE) cohort from 2017 to 2019, we examined associations between exposure to fine particulate matter (PM) and its components on infant NNS in Puerto Rico. NNS was assessed using a pacifier attached to a pressure transducer, allowing for real-time visualization of NNS amplitude, frequency, duration, cycles/burst, cycles/min and bursts/min. These data were linked to 9-month average prenatal concentrations of PM and components, measured at three community monitoring sites. We used linear regression to examine the PM-NNS association in single pollutant models, controlling for infant sex, maternal age, gestational age, and season of birth in base and additionally for household smoke exposure, age at testing, and NNS duration in full models. Among 198 infants, the average NNS amplitude and burst duration was 17.1 cmHO and 6.1 s, respectively. Decreased NNS amplitude was consistently and significantly associated with 9-month average exposure to sulfur (-1.026 ± 0.507), zinc (-1.091 ± 0.503), copper (-1.096 ± 0.535) vanadium (-1.157 ± 0.537), and nickel (-1.530 ± 0.501). Decrements in NNS frequency were associated with sulfur exposure (0.036 ± 0.018), but not other examined PM components. Our findings provide new evidence that prenatal maternal exposure to specific PM components are associated with impaired neurodevelopment in Puerto Rican infants soon after birth.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295239PMC
October 2021

Variant analyses of candidate genes in orofacial clefts in multi-ethnic populations.

Oral Dis 2021 Jun 1. Epub 2021 Jun 1.

Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA.

Objectives: Cleft lip with/without cleft palate and cleft palate only is congenital birth defects where the upper lip and/or palate fail to fuse properly during embryonic facial development. Affecting ~1.2/1000 live births worldwide, these orofacial clefts impose significant social and financial burdens on affected individuals and their families. Orofacial clefts have a complex etiology resulting from genetic variants combined with environmental covariates. Recent genome-wide association studies and whole-exome sequencing for orofacial clefts identified significant genetic associations and variants in several genes. Of these, we investigated the role of common/rare variants in SHH, RORA, MRPL53, ACVR1, and GDF11.

Materials And Methods: We sequenced these five genes in 1255 multi-ethnic cleft lip with/without palate and cleft palate only samples in order to find variants that may provide potential explanations for the missing heritability of orofacial clefts. Rare and novel variants were further analyzed using in silico predictive tools.

Results: Ninteen total variants of interest were found, with variant types including stop-gain, missense, synonymous, intronic, and splice-site variants. Of these, 3 novel missense variants were found, one in SHH, one in RORA, and one in GDF11.

Conclusion: This study provides evidence that variants in SHH, RORA, MRPL53, ACVR1, and GDF11 may contribute to risk of orofacial clefts in various populations.
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http://dx.doi.org/10.1111/odi.13932DOI Listing
June 2021

Prenatal Exposure to Glyphosate and Its Environmental Degradate, Aminomethylphosphonic Acid (AMPA), and Preterm Birth: A Nested Case-Control Study in the PROTECT Cohort (Puerto Rico).

Environ Health Perspect 2021 May 19;129(5):57011. Epub 2021 May 19.

Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.

Background: Glyphosate (GLY) is the most heavily used herbicide in the world. Despite nearly ubiquitous exposure, few studies have examined prenatal GLY exposure and potentially adverse pregnancy outcomes. Preterm birth (PTB) is a risk factor for neonatal mortality and adverse health effects in childhood.

Objectives: We examined prenatal exposure to GLY and a highly persistent environmental degradate of GLY, aminomethylphosphonic acid (AMPA), and odds of PTB in a nested case-control study within the ongoing Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) pregnancy cohort in northern Puerto Rico.

Methods: GLY and AMPA in urine samples collected at (Visit 1) and (Visit 3) wk gestation (53 cases/194 randomly selected controls) were measured using gas chromatography tandem mass spectrometry. Multivariable logistic regression was used to estimate associations with PTB (delivery completed gestation).

Results: Detection rates in controls were 77.4% and 77.5% for GLY and 52.8% and 47.7% for AMPA, and geometric means (geometric standard deviations) were 0.44 (2.50) and 0.41 for GLY and 0.25 (3.06) and 0.20 for AMPA, for Visits 1 and 3, respectively. PTB was significantly associated with specific gravity-corrected urinary GLY and AMPA at Visit 3, whereas associations with levels at Visit 1 and the Visits 1-3 average were largely null or inconsistent. Adjusted odds ratios (ORs) for an interquartile range increase in exposure at Visit 3 were 1.35 (95% CI: 0.99, 1.83) and 1.67 (95% CI: 1.26, 2.20) for GLY and AMPA, respectively. ORs for Visit 1 and the visit average were closer to the null.

Discussion: Urine GLY and AMPA levels in samples collected near the 26th week of pregnancy were associated with increased odds of PTB in this modestly sized nested case-control study. Given the widespread use of GLY, multiple potential sources of AMPA, and AMPA's persistence in the environment, as well as the potential for long-term adverse health effects in preterm infants, further investigation in other populations is warranted. https://doi.org/10.1289/EHP7295.
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http://dx.doi.org/10.1289/EHP7295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132611PMC
May 2021

Zika Prevention Behaviors Among Women of Reproductive Age in Puerto Rico, 2016.

Am J Prev Med 2021 09 2;61(3):e149-e155. Epub 2021 May 2.

Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia.

Introduction: Zika virus is primarily transmitted through mosquito bites. Because Zika virus infection during pregnancy can cause serious birth defects, reproductive-aged women need protection from Zika virus infection. This report describes Zika virus prevention behaviors among women aged 18-49 years and assesses whether pregnancy status and healthcare provider counseling increases Zika virus prevention behaviors.

Methods: A population-based cell phone survey of women aged 18-49 years living in Puerto Rico was conducted in July-November 2016. Data were analyzed in 2018-2019. Prevalence estimates and 95% CIs were calculated for Zika virus prevention behaviors. Adjusted prevalence ratios were estimated to examine the association of pregnancy status with healthcare provider counseling on Zika virus prevention behaviors, controlling for age, education, and health insurance status.

Results: Most women reported using screens on open doors/windows (87.7%) and eliminating standing water in/around their homes (92.3%). Other Zika virus prevention behaviors were less common (<33%). In adjusted analysis, pregnant women were more likely than women not at risk for unintended pregnancy to report using mosquito repellent every/most days (adjusted prevalence ratio=1.44, 95% CI=1.13, 1.85). Healthcare provider counseling was associated with receiving professional spraying/larvicide treatment (adjusted prevalence ratio=1.42, 95% CI=1.17, 1.74), sleeping under a bed net (adjusted prevalence ratio=2.37, 95% CI=1.33, 4.24), using mosquito repellent (adjusted prevalence ratio=1.57, 95% CI=1.40, 1.77), and wearing long sleeves/pants (adjusted prevalence ratio=1.32, 95% CI=1.12, 1.55).

Conclusions: Receipt of healthcare provider counseling was more consistently associated with Zika virus prevention behaviors than pregnancy status. Healthcare provider counseling is an important strategy for increasing the uptake of Zika virus prevention behaviors among women aged 18-49 years.
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http://dx.doi.org/10.1016/j.amepre.2021.03.004DOI Listing
September 2021

Individual and joint effects of phthalate metabolites on biomarkers of oxidative stress among pregnant women in Puerto Rico.

Environ Int 2021 09 23;154:106565. Epub 2021 Apr 23.

Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA. Electronic address:

Exposures to phthalate compounds have been linked to adverse birth outcomes, potentially through oxidative stress mechanisms. We explored associations between mixtures of biomarkers of phthalate and phthalate replacement metabolites and oxidative stress using lipid peroxidation biomarker 8-iso-prostaglandin-F2α (8-iso-PGF2α). As 8-iso-PGF2α can be generated via both chemical (nonenzymatic) and enzymatic lipid peroxidation pathways, we calculated the ratio of 8-iso-PGF2α/prostaglandin F2α in an attempt to distinguish the potential contributions of the two pathways. Urinary biomarker measurements were taken from 775 pregnant women in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) longitudinal birth cohort at up to three time points during gestation (16-20, 20-24, and 24-28 weeks gestation). Adaptive elastic net with pairwise linear interaction terms (adENET-I) was used to determine individual phthalate metabolites and phthalate interactions that were predictive of lipid oxidative stress biomarkers, and to subsequently create environmental risk scores (ERS) to represent weighted sums of phthalate exposure for each individual at each study visit. Repeated ERS were then used in linear mixed effects models to test for associations between biomarkers of phthalate mixtures and biomarkers of oxidative stress. We also used Bayesian kernel machine regression (BKMR) to explore nonlinearity and interactions between phthalate metabolites within the mixture. An increase from the first to fourth quartile of phthalate ERS derived from adENET-I was associated with a 96.7% increase (95% CI: 74.0, 122) in the hypothesized chemical fraction of 8-iso-PGF2α and a 268% increase (95% CI: 139, 465) in the hypothesized enzymatic fraction of 8-iso-PGF2α. BKMR analyses also suggested strong linear associations between the phthalate mixture and biomarkers of lipid oxidative stress. Various phthalates displayed nonlinear relationships with both chemical and enzymatic fractions of 8-iso-PGF2α, and we observed some evidence of interactions between metabolites in the mixture. In conclusion, exposure to phthalate mixtures was strongly associated with linear increases in biomarkers of lipid oxidative stress, and differences observed between hypothesized chemical and enzymatic lipid peroxidation outcomes highlight the need to critically assess pathways of 8-iso-PGF2α generation in relation to environmental exposures.
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http://dx.doi.org/10.1016/j.envint.2021.106565DOI Listing
September 2021

Mortality Trends in Risk Conditions and Invasive Mycotic Disease in the United States, 1999-2018.

Clin Infect Dis 2021 Apr 20. Epub 2021 Apr 20.

Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia USA.

Background: Invasive fungal infections (IFIs) in the United States are chronically underdiagnosed and a lack of coordinated surveillance makes the true burden of disease difficult to determine. The purpose of this analysis was to capture mortality-associated burden of risk conditions and fungal infections.

Methods: We analyzed data from the National Vital Statistics System from 1999-2018 to estimate the mortality attributed to risk conditions and related fungal disease.

Results: The number of risk conditions associated with fungal disease is steadily rising in the United States with 1,047,422 diagnoses at time of death in 2018. While fungal disease decreased substantially from 1999 to 2010, primarily due to the control of HIV infection, the number deaths with fungal diagnosis has increased in the non-HIV cohort, with significant increases in patients with diabetes, cancer, immunosuppressive disorders, or sepsis.

Conclusion: The landscape of individuals at risk for serious fungal diseases is changing, with a continued decline in HIV-associated incidence, but increased diagnoses in patients with cancer, sepsis, immunosuppressive disorders, and influenza. Additionally, there is an overall increase in the number of fungal infections in recent years, indicating a failure to control fungal disease mortality in these new immunocompromised cohorts. Improvement in prevention and management of fungal diseases is needed to control morbidity and mortality in the rising number of immunocompromised and at-risk patients in the United States.
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http://dx.doi.org/10.1093/cid/ciab336DOI Listing
April 2021

Maternal lipidomic signatures in relation to spontaneous preterm birth and large-for-gestational age neonates.

Sci Rep 2021 Apr 14;11(1):8115. Epub 2021 Apr 14.

Department of Environmental Health Sciences, University of Michigan, School of Public Health, 1415 Washington Heights, Ann Arbor, MI, 48109, USA.

Lipidome-wide metabolites may be useful biomarkers of pregnancy outcomes. We sought to characterize maternal lipidomic signatures associated with preterm birth and neonatal anthropometric parameters. Plasma samples were collected 24-28 weeks gestation, and lipidomic profiling was quantified using high-performance liquid chromatography tandem mass spectrometry. Lipid metabolites were analyzed individually and as whole lipid classes and subgroups based on degree of hydrocarbon chain saturation. Associations were estimated using linear and logistic regression. After false discovery adjustment (q < 0.15), four plasmenyl-phosphatidylethanolamines and three free fatty acids associated with increased risk for spontaneous preterm birth. Five phosphatidylinositols, two phosphatidylglycerols, and one phosphatidic acid were associated with large for gestational age neonates. The saturated plasmenyl-phosphatidylethanolamines held the association with increased risk for spontaneous preterm birth. Both the mono- and poly-unsaturated free fatty acids held the association for increased risk for spontaneous preterm birth. Mono- and poly-unsaturated phosphatidylinositols were associated with large for gestational age neonates. Whole lipid classes (plasmenyl-phophatidylcholines and plasmenyl-phosphatidylethanolamines) were associated with increased risk for large for gestational age at delivery. This study provides evidence that finer omics-scale analysis of the maternal lipidome may be more informative biomarkers of pregnancy outcomes compared to whole class level lipid analysis.
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http://dx.doi.org/10.1038/s41598-021-87472-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046995PMC
April 2021

Investigating the impact of Hurricane Maria on an ongoing birth cohort in Puerto Rico.

Popul Environ 2020 Sep 17;42(1):95-111. Epub 2020 Mar 17.

University of Michigan, Department of Environmental Health Sciences - Ann Arbor, Michigan.

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 US. 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.
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http://dx.doi.org/10.1007/s11111-020-00345-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967016PMC
September 2020

Psychosocial status modifies the effect of maternal blood metal and metalloid concentrations on birth outcomes.

Environ Int 2021 04 3;149:106418. Epub 2021 Feb 3.

University of Michigan School of Public Health, Department of Environmental Health Sciences, Ann Arbor, MI, United States. Electronic address:

Background: Metal exposure and psychosocial stress in pregnancy have each been associated with adverse birth outcomes, including preterm birth and low birth weight, but no study has examined the potential interaction between them.

Objectives: We examined the modifying effect of psychosocial stress on the association between metals and birth outcomes among pregnant women in Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) birth cohort study.

Methods: In our analysis of 682 women from the PROTECT study, we measured 16 essential and non-essential metals in blood samples at two time points. We administered questionnaires to collect information on depression, perceived stress, social support, and life experience during pregnancy. Using K-means clustering, we categorized pregnant women into one of two groups: "good" and "poor" psychosocial status. We then evaluated whether the effect of blood metals (geometric average) on adverse birth outcomes (gestational age, preterm birth [overall and spontaneous], birth weight z-score, small for gestation [SGA], large for gestation [LGA]) vary between two clusters of women, adjusting for maternal age, maternal education, pre-pregnancy body mass index (BMI), and second-hand smoke exposure.

Results: Blood manganese (Mn) was associated with an increased odds ratio (OR) of overall preterm birth (OR/interquartile range [IQR] = 2.76, 95% confidence interval [CI] = 1.25, 6.12) and spontaneous preterm birth (OR/IQR: 3.68, 95% CI: 1.20, 6.57) only among women with "poor" psychosocial status. The association between copper (Cu) and SGA was also statistically significant only among women having "poor" psychosocial status (OR/IQR: 2.81, 95% CI: 1.20, 6.57). We also observed associations between nickel (Ni) and preterm birth and SGA that were modified by psychosocial status during pregnancy.

Conclusions: Presence of "poor" psychosocial status intensified the adverse associations between Mn and preterm birth, Cu and SGA, and protective effects of Ni on preterm. This provides evidence that prenatal psychosocial stress may modify vulnerability to metal exposure.
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http://dx.doi.org/10.1016/j.envint.2021.106418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897320PMC
April 2021

Maternal Urinary Metal and Metalloid Concentrations in Association with Oxidative Stress Biomarkers.

Antioxidants (Basel) 2021 Jan 15;10(1). Epub 2021 Jan 15.

Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.

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.
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http://dx.doi.org/10.3390/antiox10010114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830802PMC
January 2021

Association of biomarkers of exposure to metals and metalloids with maternal hormones in pregnant women from Puerto Rico.

Environ Int 2021 02 13;147:106310. Epub 2020 Dec 13.

Department of Environmental Health Sciences, School of Public Health, University of Michigan Ann Arbor, MI, USA. Electronic address:

Background: Metal(loid)s have been associated to adverse birth outcomes in experimental and epidemiological studies, but the underlying mechanism(s) are not well understood. Endocrine disruption may be a mechanism by which the metal(loid)s impact birth outcomes.

Methods: Pregnant women were recruited through the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT). Urine, blood, demographic and pregnancy-related data were collected at recruitment and subsequent visits. Sixteen metal(loid)s were analyzed in urine and blood samples, while nine maternal hormones (corticotropin-releasing hormone (CRH), sex-hormone binding globulin (SHBG), estriol (E3), progesterone, testosterone, thyroid-stimulating hormone (TSH), total triiodothyronine (T3), total thyroxine (T4), and free thyroxine (fT4)) were measured in serum samples from 815 singleton pregnancies. Linear mixed models with random intercepts were used to examine associations between metal(loid)s in blood and urine with hormone concentrations.

Results: Arsenic blood concentrations were significantly associated with increased levels in CRH (%Δ: 23.0, 95%CI: 8.4-39.6) and decreased levels in testosterone (%Δ: 16.3, 95%CI: 26.2-5.1). Cobalt, manganese, and lead blood concentrations were associated with small increases in SHBG (%Δ range: 3.3-4.2), E3 (%Δ range: 3.9-8.7) and progesterone (%Δ range: 4.1-6.3) levels, respectively. Nickel blood concentration was inversely associated with testosterone levels (%Δ 13.3, 95%CI: 18.7-7.6). Significant interactions were detected for the association between nickel and study visit in relation to CRH (p < 0.02) and testosterone levels (p < 0.01).

Conclusion: Our analysis suggests that metal(loid)s may act as endocrine disruptors by altering prenatal hormone levels. This disruption may depend on specific windows of exposure during pregnancy. Additionally, some essential metal(loid)s such as managense and cobalt may be contributors to adverse maternal and fetal outcomes. The study of metal(loid)s as endocrine disruptors is in the early stages of epidemiological research and future studies are needed to further investigate these associations.
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http://dx.doi.org/10.1016/j.envint.2020.106310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856269PMC
February 2021

Associations between gestational weight gain and preterm birth in Puerto Rico.

BMC Pregnancy Childbirth 2020 Oct 7;20(1):599. Epub 2020 Oct 7.

Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, 101 Buck Road, GA, Athens, United States.

Background: Preterm birth (PTB; gestational age < 37 weeks) is the leading cause of infant morbidity and mortality worldwide. Low and excessive gestational weight gain (GWG) have been previously cited as risk factors for PTB, however the magnitude of association varies across populations. No studies have examined low and excessive GWG as modifiable risk factors for PTB in Puerto Rico, an area with inexplicably high PTB rates.

Methods: To examine the relationship between GWG and PTB, we conducted a retrospective analysis using birth certificate data files from the Puerto Rico Department of Health from 2005 to 2012. GWG was standardized to a 40-week gestational duration and was categorized into low, adequate, or excessive for each category of pre-pregnancy body mass index using American College of Obstetricians and Gynecologists guidelines. Logistic regression was used to determine the crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between GWG and PTB.

Results: There were 320,695 births included in this analysis; 40.6% with high GWG and 27.3% with low GWG. A greater percentage of women with low GWG were less than 20 years of age, had less than a high school education, and were underweight compared to women with adequate and excessive GWG. Women with low compared to adequate GWG had increased odds of PTB (OR = 1.34, 95% CI = 1.30-1.37). However, excessive compared to adequate GWG was not associated with PTB (OR = 0.99, 95% CI = 0.97-1.02).

Conclusions: Among women in Puerto Rico, low GWG was associated with increased odds of PTB. With the exception of obesity, these associations persisted within all strata of pre-pregnancy body mass index, highlighting the importance of maintaining a healthy weight during pregnancy. Future research should examine other factors that may contribute to GWG, such as dietary nutrients, and explore pathways through which GWG may be contributing to PTB.
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http://dx.doi.org/10.1186/s12884-020-03292-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539475PMC
October 2020

Polycyclic aromatic hydrocarbon exposure results in altered CRH, reproductive, and thyroid hormone concentrations during human pregnancy.

Sci Total Environ 2020 Dec 11;749:141581. Epub 2020 Aug 11.

Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA. Electronic address:

Polycyclic aromatic hydrocarbons (PAHs) are byproducts of incomplete combustion reactions and are ubiquitous in the environment, leading to widespread human exposure via inhalation and ingestion pathways. PAHs have been implicated as endocrine disrupting compounds in previous animal and in vitro studies, but human studies are currently lacking. Pregnant women and their developing fetuses are particularly susceptible populations to environmental contaminants, in part because alterations in hormone physiology during gestation can have adverse consequences on the health of the pregnancy. We utilized data on 659 pregnant women from the PROTECT longitudinal birth cohort in Puerto Rico to assess associations between repeated measures of 8 urinary hydroxylated PAH (OH-PAH) metabolites and 9 serum hormones during gestation. Urine samples were collected at 3 study visits (median gestational ages of 18, 22, and 26 weeks at each visit, respectively) and serum samples were collected at the first and third study visits. Linear mixed effects models were used to ascertain longitudinal associations between OH-PAHs and hormones, and sensitivity analyses were employed to assess potential nonlinearity and differences in associations on the basis of fetal sex and timing of biomarker measurement. Among the multiple positive associations we observed between OH-PAHs and CRH, estriol, progesterone, T3, and the ratio of T3 to T4, and inverse associations with testosterone, the most notable are a 24.3% increase (95% CI: 13.0, 36.7) in CRH with an interquartile range (IQR) increase in 1-hydroxyphenanthrene and a 17.2% decrease (95% CI: 8.13, 25.4) in testosterone with an IQR increase in 1-hydroxynapthalene. Many associations observed were dependent on fetal sex, and some relationships showed evidence of nonlinearity. These findings demonstrate the importance of studying PAH exposures during pregnancy and highlight the potential complexity of their impacts on the physiology of human pregnancy.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755823PMC
December 2020

Cohort profile: Center for Research on Early Childhood Exposure and Development in Puerto Rico.

BMJ Open 2020 07 19;10(7):e036389. Epub 2020 Jul 19.

Department of Civil and Environmental Engineering, Northeastern University, Boston, Massachusetts, USA.

Purpose: Puerto 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.

Participants: Infants 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 Date: Data 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 Plans: Data 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.
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http://dx.doi.org/10.1136/bmjopen-2019-036389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371225PMC
July 2020

On interdisciplinary collaboration and mentoring in Birth Defects Research.

Authors:
José F Cordero

Birth Defects Res 2020 07;112(12):955-957

Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia, USA.

There are many research societies in the world but none like the Teratology Society, now known as, the Society of Birth Defects Research and Prevention. Our Society has thrived in the last 60 years because of its inclusiveness in the diversity of disciplines of our membership, the outstanding interprofessional collaboration, and successful mentorship. This brief commentary offers some anecdotes about our diversity, interprofessional research, and mentoring.
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http://dx.doi.org/10.1002/bdr2.1691DOI Listing
July 2020

Impact of Hurricane Maria on Drinking Water Quality in Puerto Rico.

Environ Sci Technol 2020 08 23;54(15):9495-9509. Epub 2020 Jul 23.

School of Civil and Environmental Engineering, Cornell University, Ithaca, New York 14853, United States.

This study performed a comprehensive assessment of the impact of Hurricane Maria (HM) on drinking water quality in Puerto Rico (PR) by integrating targeted chemical analysis of both inorganic (18 trace elements) and organic trace pollutants (200 micropollutants) with high-throughput quantitative toxicogenomics and biomarkers-based toxicity assays. Average concentrations of 14 detected trace elements and 20 organic micropollutants showed elevation after HM. Arsenic, sucralose, perfluorooctanoic acid (PFOA), atrazine-2-hydroxy, benzotriazole, acesulfame, and prometon were at significantly ( < 0.05) higher levels in the post-HM than in the pre-HM samples. Thirteen micropollutants, including four pesticides, were only detected in posthurricane samples. Spatial comparison showed higher pollutant and toxicity levels in the samples from northern PR (where eight Superfund sites are located) than in those from southern PR. Distinctive pathway-specific molecular toxicity fingerprints for water extracts before and after HM and at different locations revealed changes in toxicity nature that likely resulted from the impact of HM on drinking water composition. Correlation analysis and Maximum Cumulative Ratio assessment suggested that metals (i.e., arsenic) and PFOA were the top ranked pollutants that have the potential to cause increased risk after HM, providing a possible direction for future water resource management and epidemiological studies.
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http://dx.doi.org/10.1021/acs.est.0c01655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837318PMC
August 2020

Non-random distribution of deleterious mutations in the DNA and protein-binding domains of IRF6 are associated with Van Der Woude syndrome.

Mol Genet Genomic Med 2020 08 17;8(8):e1355. Epub 2020 Jun 17.

School of Public Health, Addis Ababa University, Addis Ababa, Ethiopia.

Background: The development of the face occurs during the early days of intrauterine life by the formation of facial processes from the first Pharyngeal arch. Derangement in these well-organized fusion events results in Orofacial clefts (OFC). Van der Woude syndrome (VWS) is one of the most common causes of syndromic cleft lip and/or palate accounting for 2% of all cases. Mutations in the IRF6 gene account for 70% of cases with the majority of these mutations located in the DNA-binding (exon 3, 4) or protein-binding domains (exon 7-9). The current study was designed to update the list of IRF6 variants reported for VWS by compiling all the published mutations from 2013 to date as well as including the previously unreported VWS cases from Africa and Puerto Rico.

Methods: We used PubMed with the search terms; "Van der Woude syndrome," "Popliteal pterygium syndrome," "IRF6," and "Orofacial cleft" to identify eligible studies. We compiled the CADD score for all the mutations to determine the percentage of deleterious variants.

Results: Twenty-one new mutations were identified from nine papers. The majority of these mutations were in exon 4. Mutations in exon 3 and 4 had CADD scores between 20 and 30 and mutations in exon 7-9 had CADD scores between 30 and 40. The presence of higher CADD scores in the protein-binding domain (exon 7-9) further confirms the crucial role played by this domain in the function of IRF6. In the new cases, we identified five IRF6 mutations, three novel missense mutations (p.Phe36Tyr, p.Lys109Thr, and p.Gln438Leu), and two previously reported nonsense mutations (p.Ser424*and p.Arg250*).

Conclusion: Mutations in the protein and DNA-binding domains of IRF6 ranked among the top 0.1% and 1% most deleterious genetic mutations, respectively. Overall, these findings expand the range of VWS mutations and are important for diagnostic and counseling purposes.
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http://dx.doi.org/10.1002/mgg3.1355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434609PMC
August 2020

Assessment of contraceptive use in Puerto Rico during the 2016 Zika virus outbreak.

Contraception 2020 06 17;101(6):405-411. Epub 2020 Mar 17.

Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, GA, United States.

Objectives: The objectives of this analysis were to 1) estimate prevalence of contraceptive use among women at risk for unintended pregnancy and 2) identify correlates of contraceptive use among women with ongoing or potential need for contraceptive services in Puerto Rico during the 2016 Zika virus (ZIKV) outbreak.

Study Design: We conducted a cell-phone survey July-November, 2016. Women aged 18-49 years living in Puerto Rico were eligible. We completed 3059 interviews; the overall response rate was 69.2%. After weighting, the data provide population-based estimates. For this analysis, we included women at risk for unintended pregnancy, and assessed ongoing or potential need for contraceptive services in this group, excluding women using permanent contraceptive methods.

Results: Most women reported using contraception (82.8%), and use increased with age. Female sterilization and male condoms were most frequently reported (40.8% and 17.1%, respectively). Among women with ongoing or potential need for contraceptive services, 24.7% talked to a healthcare provider about ZIKV, and 31.2% reported a change in childbearing intentions due to ZIKV. Most women were at least a little worried about getting infected with ZIKV (74.3%) or having a baby with a birth defect (80.9%). Being very worried about getting infected with ZIKV and already having Zika were significantly associated with use of any contraception (adjusted prevalence ratio: 1.19, 95% CI: 1.03-1.38 and 1.32, 95% CI: 1.01-1.72, respectively).

Conclusions: These findings underscore the need for regular contraceptive prevalence studies to inform programs about contraceptive needs, especially during public health emergencies.

Implications: When the 2016 Zika virus outbreak began in Puerto Rico there were no recent population-based data available on contraceptive prevalence. To fill this information gap, we conducted a population-based survey. Our findings provided baseline contraceptive prevalence estimates to support response planning and allocation of health resources.
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http://dx.doi.org/10.1016/j.contraception.2020.03.001DOI Listing
June 2020

Maternal blood metal and metalloid concentrations in association with birth outcomes in Northern Puerto Rico.

Environ Int 2020 05 13;138:105606. Epub 2020 Mar 13.

University of Michigan School of Public Health, Department of Environmental Health Sciences, Ann Arbor, MI, United States. Electronic address:

Background: In previous studies, exposures to heavy metals such as Pb and Cd have been associated with adverse birth outcomes; however, knowledge on effects at low levels of exposure and of other elements remain limited.

Method: We examined individual and mixture effects of metals and metalloids on birth outcomes among 812 pregnant women in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort. We measured 16 essential and non-essential metal(loid)s in maternal blood collected at 16-20 and 24-28 weeks gestation. We used linear and logistic regression to independently examine associations between geometric mean (GM) concentrations of each metal across visits and gestational age, birthweight z-scores, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). We evaluated effect modification with infant sex*metal interaction terms. To identify critical windows of susceptibility, birth outcomes were regressed on visit-specific metal concentrations. Furthermore, average metal concentrations were divided into tertiles to examine the potential for non-linear relationships. We used elastic net (ENET) regularization to construct Environmental Risk Score (ERS) as a metal risk score and Bayesian Kernel Machine Regression (BKMR) to identify individual metals most critical to each outcome, accounting for correlated exposures.

Results: In adjusted models, an interquartile range (IQR) increase in GM lead (Pb) was associated with 1.63 higher odds of preterm birth (95%CI = 1.17, 2.28) and 2 days shorter gestational age (95% CI = -3.1, -0.5). Manganese (Mn) and zinc (Zn) were also associated with higher odds of preterm birth and shorter gestational age; the associations were strongest among the highest tertile for Mn and among females for Zn. Mercury (Hg) was associated with higher risk of preterm birth at the later window of pregnancy. Ni measured later in pregnancy was associated with lower odds of SGA. ENET and BKMR models selected similar metals as "important" predictors of birth outcomes. The association between ERS and preterm birth was assessed and the third tertile of ERS was significantly associated with an elevated odds ratio of 2.13 (95% CI = 1.12, 5.49) for preterm birth compared to the first tertile.

Conclusion: As the PROTECT cohort has lower Pb concentrations (GM = 0.33 μg/dL) compared to the mainland US, our findings suggest that low-level prenatal lead exposure, as well as elevated Mn and Zn exposure, may adversely affect birth outcomes. Improved understanding on environmental factors contributing to preterm birth, together with sustainable technologies to remove contamination, will have a direct impact in Puerto Rico and elsewhere.
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http://dx.doi.org/10.1016/j.envint.2020.105606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198231PMC
May 2020

Documenting the Public Health Impacts of the Serial Hurricanes of 2017.

Disaster Med Public Health Prep 2020 02;14(1):3-4

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http://dx.doi.org/10.1017/dmp.2020.19DOI Listing
February 2020

The Caribbean Strong Summit: Building Resilience With Equity.

Disaster Med Public Health Prep 2020 02;14(1):155-157

Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia.

The objective of the Caribbean Strong Summit was to plan an intersectoral summit to address the equity of community health and resilience for disaster preparedness, response and recovery and develop a set of integrated and actionable recommendations for Puerto Rico and the Caribbean Region post Hurricanes Irma and Maria. A three-day meeting was convened with a wide range of community, organizational and private sector leaders along with representatives from Puerto Rico, the Caribbean, the Americas, and global experts to generate recommendations for enhanced resilience based upon lessons learned and evidence-based approaches. More than 500 participants from the region gave 104 presentations with recommendations for resilience. Over 150 recommendations were generated and ranked for importance and actionability by participants. A representative sample of these are presented along with five major themes for building health resilient communities in the Caribbean. This summit was successful in compiling a set of integrated recommendations from more than 19 diverse sectors and in defining five major thematic areas for future work to enhance resilience for all types of future disasters. A follow-up meeting should be planned to continue this discussion and to showcase work that has been accomplished in these areas. A complete set of the recommendations from the Caribbean Strong Summit and their analysis and compilation would be published and should serve as a foundational effort to enhance preparedness and resiliency towards future disasters in the Caribbean.
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http://dx.doi.org/10.1017/dmp.2020.18DOI Listing
February 2020

Predictors of urinary and blood Metal(loid) concentrations among pregnant women in Northern Puerto Rico.

Environ Res 2020 04 23;183:109178. Epub 2020 Jan 23.

University of Michigan School of Public Health, Department of Environmental Health Sciences, Ann Arbor, MI, United States. Electronic address:

Given the potential adverse health effects related to toxic trace metal exposure and insufficient or excessive levels of essential trace metals in pregnant women and their fetuses, the present study characterizes biomarkers of metal and metalloid exposure at repeated time points during pregnancy among women in Puerto Rico. We recruited 1040 pregnant women from prenatal clinics and collected urine, blood, and questionnaire data on demographics, product use, food consumption, and water usage at up to three visits. All samples were analyzed for 16 metal(loid)s: arsenic (As), barium (Ba), beryllium (Be), cadmium (Cd), cobalt (Co), chromium (Cr), cesium (Cs), copper (Cu), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), titanium (Ti), uranium (U), vanadium (V), and zinc (Zn). Urine samples were additionally analyzed for molybdenum (Mo), platinum (Pt), antimony (Sb), tin (Sn), and tungsten (W). Mean concentrations of most metal(loid)s were higher among participants compared to the general US female population. We found weak to moderate correlations for inter-matrix comparisons, and moderate to strong correlations between several metal(loid)s measured within each biological matrix. Blood concentrations of Cu, Zn, Mn, Hg, and Pb were shown to reflect reliable biomarkers of exposure. For other metals, repeated samples are recommended for exposure assessment in epidemiology studies. Predictors of metal(loid) biomarkers included fish and rice consumption (urinary As), fish and canned food (blood Hg), drinking public water (blood Pb), smoking (blood Cd), and iron/folic acid supplement use (urinary Cs, Mo, and Sb). Characterization of metal(loid) biomarker variation over time and between matrices, and identification of important exposure sources, may inform future epidemiology studies and exposure reduction strategies.
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http://dx.doi.org/10.1016/j.envres.2020.109178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167342PMC
April 2020

Relationships between psychosocial factors during pregnancy and preterm birth in Puerto Rico.

PLoS One 2020 29;15(1):e0227976. Epub 2020 Jan 29.

Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, United States of America.

Psychosocial stress during pregnancy has been associated with adverse pregnancy outcomes including preterm birth (PTB). This has not been studied in Puerto Rico, an area with high PTB rates. Our objective was to develop a conceptual model describing the interrelationships between measures of psychosocial stress and depression, a result of stress, among pregnant women in Puerto Rico and to examine their associations with PTB. We used data from the Puerto Rico Testsite for Exploring Contamination Threats pregnancy cohort (PROTECT, N = 1,047) to examine associations among depression and different continuous measures of psychosocial stress using path analysis. Psychosocial stress during pregnancy was assessed using validated measures of perceived stress, negative life experiences, neighborhood perceptions and social support. Logistic regression was used to examine associations between psychosocial stress measures in tertiles and PTB. Perceived stress, negative life experiences, and neighborhood perceptions influenced depression through multiple pathways. Our model indicated that perceived stress had the strongest direct effect on depression, where one standard deviation (SD) increase in perceived stress was associated with a 57% SD increase in depression. Negative life experiences were directly but also indirectly, through perceived stress, associated with depression. Finally, neighborhood perceptions directly influenced negative life experiences and perceived stress and consequently had an indirect effect on depression. Psychosocial stress was not associated with PTB across any of the measures examined. Our study examined interrelationships between multiple measures of psychosocial stress and depression among a pregnant Puerto Rican population and identified negative neighborhood perceptions as important upstream factors leading to depression. Our findings highlight the complex relationship between psychosocial stress measures and indicate that psychosocial stress and depression, assessed using 5 different scales, were not associated with PTB. Future research should investigate other environmental and behavioral risk factors contributing to higher rates of PTB in this population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227976PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988967PMC
April 2020

Influenza Vaccine Efficacy and Effectiveness in Pregnant Women: Systematic Review and Meta-analysis.

Matern Child Health J 2020 Feb;24(2):229-240

Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, GA, 30602, USA.

Objective: Pregnant women have a high risk for complications from influenza infection, but vaccination rates within this group remain low in the US and other countries. The efficacy and effectiveness of the influenza vaccine are a key determinant of vaccine uptake. This review aimed to synthesize the available evidence on the protection of both seasonal and monovalent pandemic H1N1 (pdmH1N1) vaccine against laboratory-confirmed influenza (LCI), influenza-like illness (ILI), and respiratory illness (RI).

Methods: A search of the literature was undertaken from Pubmed, Embase, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials up to Aug 1, 2018. Both observational studies and clinical trials were considered.

Results: Nineteen studies were identified from 11 countries. Women with pdmH1N1 vaccination had a lower risk of getting LCI (Relative risk [RR] 0.3, 95% confidence interval [CI] 0.26-0.35) and ILI (RR 0.15, 95% CI 0.06-0.36)). The pooled estimate from three randomized clinical trials (RR 0.47, 95% CI 0.31-0.71) and two case control studies (OR 0.37, 95% CI 0.23-0.61) showed that the seasonal vaccine was protective against LCI. The seasonal vaccine was not protective against ILI (RR 0.95, 95% CI 0.88-1.03). This association was similar for the outcome of RI (RR 0.81, 95% CI 0.55-1.20).

Conclusion: This analysis bolsters existing evidence that influenza vaccines are effective among pregnant women. Additional public health efforts are needed to promote physician recommendations of influenza vaccination in pregnancy.
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http://dx.doi.org/10.1007/s10995-019-02844-yDOI Listing
February 2020

The effect of leptin on blood pressure considering smoking status: a Mendelian randomization study.

Hypertens Res 2020 04 12;43(4):342-349. Epub 2019 Dec 12.

Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, 120 B.S. Miller Hall, Health Sciences Campus, 101 Buck Road, Athens, GA, 30602, USA.

Studies on leptin and blood pressure (BP) associations have yielded inconsistent findings. The current study aimed to evaluate the effect of genetically determined leptin on BP and to explore whether smoking status modified this effect. We conducted a Mendelian randomization analysis using the baseline data of 3860 participants in the Framingham Heart Study 3rd generation cohort. Pairwise associations among leptin genetic risk score (GRS), log-transformed leptin (log-leptin), and BP were assessed by multivariate linear regression models. Age and sex were adjusted in the base model, and education, smoking, drinking, and physical activity were adjusted in the full model. The interaction between leptin GRS and smoking was evaluated by adding an interaction term, GRS × smoking, in the fully adjusted model. In the age- and sex-adjusted analyses, log-leptin was positively associated with systolic BP (SBP) (P = 2.35 × 10), diastolic BP (DBP) (P = 6.19 × 10), mean arterial pressure (MAP) (P = 1.10 × 10), and pulse pressure (P = 4.38 × 10). Leptin GRS significantly increased log-leptin (P = 0.00001). Leptin GRS was associated with reduced SBP (P = 0.04), DBP (P = 0.006), and MAP (P = 0.008) among current smokers. In the fully adjusted model, significant interactions between GRS and smoking were identified for SBP (P = 0.02), DBP (P = 0.002), and MAP (P = 0.003). Sensitivity analyses among participants not taking antihypertensive or glucose-lowering medications revealed similar associations. Our study provided evidence for a potentially causal relationship between leptin and BP among current smokers.
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http://dx.doi.org/10.1038/s41440-019-0376-6DOI Listing
April 2020

Interactions between chemicals and non-chemical stressors: The modifying effect of life events on the association between triclocarban, phenols and parabens with gestational length in a Puerto Rican cohort.

Sci Total Environ 2020 Mar 31;708:134719. Epub 2019 Oct 31.

Department of Environmental Health Sciences, University of Michigan, School of Public Health, Ann Arbor, MI, USA. Electronic address:

Background: Phenols and parabens are common additives to consumer products. There is evidence of adverse birth outcomes in association with prenatal exposure to these chemicals, in addition to psychosocial factors. We previously reported an increase in gestational length with bisphenol-A, methylparaben and propylparaben, and a decrease in gestational length with triclocarban.

Objectives: We examined the modifying effect of psychosocial stress on the association between chemicals and gestational length in up to 752 women among a pregnancy cohort study.

Methods: Urinary biomarkers were measured at up to three time points in pregnancy. Multiple linear regression models were conducted to investigate the association between gestational length and the interaction between average exposure biomarkers and LES. Multiple linear regression models regressing the exposure biomarkers in relation to gestational length were also stratified by LES, Negative LES, and Positive LES, based on the subjective ratings of events. Results were transformed into the change in gestational length for an inter-quartile-range difference in the exposure.

Results: Of the four psychosocial stress measures, only the life events score (LES) was a significant modifier. Associations between triclocarban, bisphenol-S, methyl- and propylparaben in relation to gestational length were stronger among women with negative Total LES scores. Among women with negative Total LES scores, bisphenol-S and triclocarban were associated with a 3-5 day decrease in gestational length [(-3.15; 95% CI: -6.06, -0.24); (-4.68; 95% CI: -8.47, -0.89)], whereas methylparaben and propylparaben were associated with a 2-3 day increase in gestational length [(2.21; 95% CI: 0.02, 4.40); (2.92; 95% CI: 0.58, 5.26)]. Significant interactions were driven by negative life events, but the association with triclocarban was driven by few positive life events.

Conclusions: Associations between exposure biomarkers and gestational length were stronger in the presence of negative life events. This provides evidence that stress makes the body more vulnerable to chemical exposure.
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http://dx.doi.org/10.1016/j.scitotenv.2019.134719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957748PMC
March 2020
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