Genome-wide association study reveals shared and distinct genetic architecture of fatty acids and oxylipins in the Hispanic Community Health Study/Study of Latinos.

Bioactive fatty acid-derived oxylipin molecules play key roles mediating inflammation and oxidative stress. Circulating levels of fatty acids and oxylipins are influenced by environmental and genetic factors; characterizing the genetic architecture of bioactive lipids could yield new insights into underlying biology. We performed a genome-wide association study (GWAS) of 81 fatty acids and oxylipins in 11,584 Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants with genetic and lipidomic data measured at study baseline (58.

Exposure to organophosphate ester flame retardants and plasticizers and associations with preeclampsia and blood pressure in pregnancy.

Background: Organophosphate esters (OPEs), flame retardants and plasticizers found widely in consumer products, may impact vascularization processes in pregnancy. Yet, the association between maternal exposure to OPEs and both preeclampsia and blood pressure during pregnancy remains understudied.

Methods: Within the LIFECODES Fetal Growth Study (N = 900), we quantified 8 OPE metabolites from maternal urine collected at up to 3 time points during pregnancy and created within-subject geometric means.

Organophosphate Ester Flame Retardants and Plasticizers in Relation to Fetal Growth in the LIFECODES Fetal Growth Study.

Background: Organophosphate esters (OPEs), used ubiquitously as flame retardants and plasticizers in consumer products, are suspected of having developmental toxicity.

Objectives: Our study aimed to estimate associations between prenatal exposure to OPEs and fetal growth, including both ultrasound (head circumference, abdominal circumference, femur length, and estimated fetal weight) and delivery [birth weight -score, small-for-gestational age (SGA), and large-for-gestational age (LGA)] measures of growth.

Methods: In the LIFECODES Fetal Growth Study (2008-2018), an enriched case-cohort of 900 babies born at the small and large ends of the growth spectrum, we quantified OPE biomarkers in three urine samples per pregnant participant and abstracted ultrasound and delivery measures of fetal growth from medical records.

Genome-wide association study reveals shared and distinct genetic architecture underlying fatty acid and bioactive oxylipin metabolites in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Bioactive fatty acid-derived oxylipin molecules play key roles in mediating inflammation and oxidative stress, which underlie many chronic diseases. Circulating levels of fatty acids and oxylipins are influenced by both environmental and genetic factors; characterizing the genetic architecture of bioactive lipids could yield new insights into underlying biological pathways. Thus, we performed a genome wide association study (GWAS) of n=81 fatty acids and oxylipins in n=11,584 Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants with genetic and lipidomic data measured at study baseline (58.

Racial and Ethnic Disparities in Phthalate Exposure and Preterm Birth: A Pooled Study of Sixteen U.S. Cohorts.

Background: Phthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth.

Objectives: We investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: ) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and ) exposure-response models stratified by race and ethnicity.

Methods: We pooled individual-level data on 6,045 pregnancies from 16 U.

Maternal exposure to phthalates and total gestational weight gain in the LIFECODES birth cohort.

Excessive gestational weight gain contributes to adverse maternal and neonatal outcomes. Environmental exposures such as phthalates may lead to metabolic dysregulation, and studies suggest possible associations between maternal phthalate exposure and altered gestational weight gain. We assessed the association between nine maternal phthalate metabolites and measures of total gestational weight gain (pre-pregnancy to median 35.

Fetal growth trajectories of babies born large-for-gestational age in the LIFECODES Fetal Growth Study.

Background: Babies born large-for-gestational age have an increased risk of adverse health outcomes, including birth injuries, childhood obesity, and cardiometabolic disorders. However, little work has been done to characterize patterns of fetal growth among large-for-gestational age births, which may further elucidate high- and low-risk subgroups.

Objective: This study aimed to identify subgroups of large-for-gestational age births based on trajectories of fetal growth derived from prenatal ultrasound measurements and explore differences in sociodemographic, pregnancy, and birth outcome characteristics across subgroups.

An application of group-based trajectory modeling to define fetal growth phenotypes among small-for-gestational-age births in the LIFECODES Fetal Growth Study.

Background: Reductions in fetal growth are associated with adverse outcomes at birth and later in life. However, identifying fetuses with pathologically small growth remains challenging. Definitions of small-for-gestational age are often used as a proxy to identify those experiencing pathologic growth (ie, fetal growth restriction).

Associations Between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth: A Pooled Study of 16 US Cohorts.

Importance: Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth.

Objective: To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US.

Design, Setting, And Participants: Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US.

Associations between social, biologic, and behavioral factors and biomarkers of oxidative stress during pregnancy: Findings from four ECHO cohorts.

Background: Lower socioeconomic status (SES) and elevated psychosocial stress are known contributors to adverse pregnancy outcomes; however, biological mechanisms linking these factors to adverse pregnancy outcomes are not well-characterized. Oxidative stress may be an important, yet understudied mechanistic pathway. We used a pooled study design to examine biological, behavioral, and social factors as predictors of prenatal oxidative stress biomarkers.

Combining Urinary Biomarker Data From Studies With Different Measures of Urinary Dilution.

Background: Guidance is lacking for how to combine urinary biomarker data across studies that use different measures of urinary dilution, that is, creatinine or specific gravity.

Methods: Among 741 pregnant participants from four sites of The Infant Development and Environment Study (TIDES) cohort, we assessed the relation of maternal urinary di-2-ethylhexyl phthalate (DEHP) concentrations with preterm birth. We compared scenarios in which all sites measured either urinary creatinine or specific gravity, or where measure of dilution differed by site.

Inflammation and oxidative stress as mediators of the impacts of environmental exposures on human pregnancy: Evidence from oxylipins.

Inflammation and oxidative stress play major roles in healthy and pathological pregnancy. Environmental exposure to chemical pollutants may adversely affect maternal and fetal health in pregnancy by dysregulating these critical underlying processes of inflammation and oxidative stress. Oxylipins are bioactive lipids that play a major role in regulating inflammation and increasing lines of evidence point towards an importance in pregnancy.

Longitudinal exposure to consumer product chemicals and changes in plasma oxylipins in pregnant women.

Background: Exposure to consumer product chemicals during pregnancy may increase susceptibility to pregnancy disorders by influencing maternal inflammation. However, effects on specific inflammatory pathways have not been well characterized. Oxylipins are a diverse class of lipids that act as important mediators and biomarkers of several biological pathways that regulate inflammation.

Urinary polycyclic aromatic hydrocarbons concentrations and hepatitis B antibody serology in the United States (NHANES, 2003-2014).

Background: Polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants that are hepatotoxic and immunotoxic. PAH exposure may modulate hepatitis B immunology.

Objective: We used data from 6 cycles of the National Health and Nutrition Examination Survey (2003-2014) to evaluate the associations between urinary PAH metabolites and hepatitis B serology.

Longitudinal profiles of plasma eicosanoids during pregnancy and size for gestational age at delivery: A nested case-control study.

Background: Inflammation during pregnancy is hypothesized to influence fetal growth. Eicosanoids, an important class of lipid mediators derived from polyunsaturated fatty acids, can act as both direct influences and biomarkers of inflammation through a variety of biological pathways. However, quantifying these distinct inflammatory pathways has proven difficult.

A prospective cohort study of in utero and early childhood arsenic exposure and infectious disease in 4- to 5-year-old Bangladeshi children.

Background: Previous research found that infants who were exposed to high levels of arsenic in utero had an increased risk of infectious disease in the first year of life. This prospective study examined the association between arsenic exposures during gestation, and respiratory, diarrheal, and febrile morbidity in children 4-5 years of age.

Methods: A cohort of pregnant women was recruited in 2008-2011 in Bangladesh.

Evaluating the effects between metal mixtures and serum vaccine antibody concentrations in children: a prospective birth cohort study.

Background: Many populations are exposed to arsenic, lead, and manganese. These metals influence immune function. We evaluated the association between exposure to single and multiple metals, including arsenic, lead, and manganese, to humoral immunity as measured by antibody concentrations to diphtheria and tetanus toxoid among vaccinated Bangladeshi children.

Arsenic exposure and serum antibody concentrations to diphtheria and tetanus toxoid in children at age 5: A prospective birth cohort in Bangladesh.

Background: Arsenic can impair immune function. Timing of exposure can influence potential immunotoxicity of arsenic exposure. We examined the association between drinking water arsenic concentrations (W-As) measured repeatedly during different exposure windows in early life and serum concentrations of IgG antibodies against diphtheria and tetanus toxoids (diphtheria and tetanus antibody).

Cross sectional association of arsenic and seroprevalence of hepatitis B infection in the United States (NHANES 2003-2014).

Background: Arsenic alters immunological parameters including antibody formation and antigen-driven T-cell proliferation.

Objective: We evaluated the cross-sectional relationship between urinary arsenic and the seroprevalence of hepatitis B (HBV) infection in the United States using data from six pooled cycles of the National Health and Nutrition Examination Survey (2003-2014, N = 12,447).

Methods: Using serological data, participants were classified as susceptible, immune due to vaccination, or immune due to past natural infection.

Trends in urinary arsenic among the U.S. population by drinking water source: Results from the National Health and Nutritional Examinations Survey 2003-2014.

Background: In 2001, the United States revised the arsenic maximum contaminant level for public drinking water systems from 50µg/L to 10µg/L. This study aimed to examine temporal trends in urinary arsenic concentrations in the U.S.

Monomethylarsonous acid, but not inorganic arsenic, is a mitochondria-specific toxicant in vascular smooth muscle cells.

Arsenic exposure has been implicated as a risk factor for cardiovascular diseases, metabolic disorders, and cancer, yet the role mitochondrial dysfunction plays in the cellular mechanisms of pathology is largely unknown. To investigate arsenic-induced mitochondrial dysfunction in vascular smooth muscle cells (VSMCs), we exposed rat aortic smooth muscle cells (A7r5) to inorganic arsenic (iAs(III)) and its metabolite monomethylarsonous acid (MMA(III)) and compared their effects on mitochondrial function and oxidative stress. Our results indicate that MMA(III) is significantly more toxic to mitochondria than iAs(III).