Phthalate exposure increases interferon-γ during pregnancy: The Atlanta African American Maternal-Child Cohort.

BACKGROUND: The immune system undergoes unique adaptations during pregnancy and is particularly sensitive to environmental chemicals, such as phthalates, which are associated with acute and chronic inflammatory medical conditions. However, current knowledge of how phthalate exposures are associated with systemic inflammation in pregnant people is limited by cross-sectional study designs and single chemical models. Our objective was to estimate the association between repeated measures of prenatal phthalate exposures, examined individually and collectively, and a panel of clinical inflammatory biomarkers. METHODS: In the Atlanta African American Maternal-Child Cohort, biospecimens were collected at mean 11 and 26 weeks gestation (N = 126). Concentrations of eight urinary phthalate metabolites and five serum inflammatory biomarkers, including CRP, IFN-γ, IL-6, IL-10, and TNF-α, were measured. Linear mixed effect regression and quantile g-computation models were used to estimate the associations for single phthalates and their exposure mixture, respectively. RESULTS: Participants who self-reported any use of alcohol, tobacco, or marijuana in the month prior to pregnancy had increased MEP, MBP, MiBP, and CRP, relative to those with no substance use. IFN-γ was elevated in response to MECPP (% change = 17.35, 95 % confidence interval [CI] = 0.32, 32.27), MEHHP (% change = 12.75, 95 % CI = 2.22, 24.36), MEOHP (% change = 11.63, 95 % CI = 1.21, 23.12), and their parent phthalate, ΣDEHP (% change = 15.03, 95 % CI = 0.28, 31.94). The phthalate mixture was also associated with an increase in IFN-γ (% change = 15.03, 95 % CI = 6.18, 24.61). CONCLUSIONS: Our findings suggest DEHP metabolites induce systemic inflammation during pregnancy. The pro-inflammatory cytokine IFN-γ may play an important role in the relationship between prenatal phthalate exposures and adverse pregnancy outcomes.

Prenatal exposure to persistent and non-persistent chemical mixtures and associations with adverse birth outcomes in the Atlanta African American Maternal-Child Cohort.

BACKGROUND: African Americans (AAs) experience higher rates of preterm birth and fetal growth restriction relative to other pregnant populations. Differential in utero exposure to environmental chemicals may partially explain these health disparities, as AAs are disproportionately exposed to environmental hazards. OBJECTIVE: We examined the individual and mixture effects of non-persistent chemicals and persistent organic pollutants (POPs) on gestational age at birth and birthweight for gestational age z-scores within a prospective cohort of pregnant AAs. METHODS: First-trimester serum and urine samples obtained from participants within the Atlanta African American Maternal-Child cohort were analyzed for 43 environmental chemicals, including per-and polyfluoroalkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides, pyrethroid insecticides, phthalates, bisphenol A, nicotine, and the primary metabolite of delta-9-tetrahydrocannabinol. Linear regression was used to estimate individual associations between chemicals and gestational age and birthweight z-scores (N ranging from 107 to 523). Mixture associations were estimated using quantile g-computation, principal component (PC) analyses, and hierarchical Bayesian kernel machine regression among complete cases (N = 86). RESULTS: Using quantile g-computation, increasing all chemical exposures by one quantile was modestly associated with a reduction in gestational age (mean change per quartile increase = -0.47, 95% CI = -1.56, 0.61) and birthweight z-scores (mean change per quartile increase = -0.49, 95% CI = -1.14, 0.15). All PCs were associated with a reduction in birthweight z-scores; associations were greatest in magnitude for the two PCs reflecting exposure to combined tobacco, insecticides, PBDEs, and phthalates. In single pollutant models, we observed inconsistent and largely non-significant associations. SIGNIFANCE: We conducted multiple targeted exposure assessment methods to quantify levels of environmental chemicals and leveraged mixture methods to quantify their joint effects on gestational age and birthweight z-scores. Our findings suggest that prenatal exposure to multiple classes of persistent and non-persistent chemicals is associated with reduced gestational age and birthweight z-scores in AAs. IMPACT: African Americans (AAs) experience higher rates of preterm birth and fetal growth restriction relative to other pregnant populations. Differential in utero exposure to environmental chemicals may partially explain these health disparities, as AAs are disproportionately exposed to environmental hazards. In the present study, we analyzed serum and urine samples for levels of 43 environmental chemicals. We used quantile g-computation, principal component analysis, and BKMR to assess associations between chemical exposure mixtures and adverse birth outcomes. Our findings suggest that prenatal exposure to multiple classes of chemicals is associated with reduced birthweight z-scores, a proxy for fetal growth, in AAs.

The effect of race and co-morbidities on Alzheimer's disease based on Medicare data.

INTRODUCTION: Alzheimer's disease (AD) incidence is thought to be higher among Black than White individuals. METHODS: We studied the US Medicare population from 2000 to 2018. Cox regression was used to determine the roles of race and co-morbidities for AD incidence. RESULTS: We studied 11,880,906 Medicare beneficiaries, with 774,548 AD cases. Hazard ratios (HRs) by increasing numbers of co-morbidities (1-7) were 1.51, 2.00, 2.55, 3.16, 2.89, 4.77, and 5.65. Among those with no co-morbidities, Black individuals had a lower rate than those who are White (HR = 0.69), while among those with one more co-morbidities, Black individuals had a higher rate (HR = 1.19). The presence of hypertension increased AD rates by 14% for White individuals, but 69% for those who are Black. DISCUSSION: More co-morbidities was strongly associated with higher AD rates. The higher rates for Black versus White individuals was apparent only for those with co-morbidities and appears driven both by more co-morbidities, and the greater effect of hypertension. HIGHLIGHTS: Black individuals have been shown to have higher Alzheimer's disease (AD) rates than those who are White. Some co-morbidities are known to increase AD risk. Among those In Medicare data with no co-morbidities, Black individuals have less risk than those who are White. Among those with co-morbidities, Black individuals have higher rates than those who are White. Hypertension results in a much stronger increase in AD risk for Black versus White individuals.

Per- and polyfluoroalkyl substances and psychosocial stressors have a joint effect on adverse pregnancy outcomes in the Atlanta African American Maternal-Child cohort.

BACKGROUND: African Americans (AAs) experience high rates of adverse pregnancy outcomes relative to Whites. Differential in utero exposure to environmental chemicals and psychosocial stressors may explain some of the observed health disparities, as exposures to per- and polyfluoroalkyl substances (PFAS) and experiences of discrimination have been linked to adverse birth outcomes. Few studies have examined chemicals and non-chemical stressors together as an exposure mixture, which may better reflect real-life exposure patterns. Here, we adapted methods designed for the analysis of exposure mixtures to examine joint effects of PFAS and psychosocial stress on birth outcomes among AAs. METHODS: 348 participants from the Atlanta African American Maternal-Child cohort were included in this study. Four PFAS were measured in first trimester serum samples. Self-report questionnaires were administered during the first trimester and were used to assess psychosocial stress (perceived stress, depression, anxiety, gendered racial stress). Quantile g-computation and Bayesian kernel machine regression (BKMR) were used to estimate the joint effects between PFAS and psychosocial stressors on gestational age at delivery and birthweight for gestational age z-scores. All models were adjusted for maternal education, maternal age, parity, and any alcohol, tobacco and marijuana use. RESULTS: Our analytic sample included a socioeconomically diverse group of pregnant women, with 79 % receiving public health insurance. In quantile g-computation models, a simultaneous one-quartile increase in all PFAS, perceived stress, depression, anxiety, and gendered racial stress was associated with a reduction in birthweight z-scores (mean %change per quartile increase = -0.24, 95 % confidence interval = -0.43, -0.06). BKMR similarly showed that increasing all exposures in the mixture was associated with a modest decrease in birthweight z-scores, but not a reduced length of gestation. DISCUSSION: Using methods designed for analyzing exposure mixtures, we found that a simultaneous increase in in utero PFAS and psychosocial stressors was associated with reduced birthweight for gestational age z-scores.

Assessment of metabolic perturbations associated with exposure to phthalates among pregnant African American women.

BACKGROUND: Phthalates have been linked with numerous harmful health effects. Limited data are available on the molecular mechanism underlying phthalate toxicity on human health. In this study, we measured urinary phthalate metabolites and used high-resolution metabolomics (HRM) to identify biological perturbations associated with phthalate exposures among pregnant African American (AA) women, who are disproportionately exposed to high phthalates levels. METHODS: We used untargeted HRM profiling to characterize serum samples collected during early (8-14 weeks gestation) and late (24-30 weeks gestation) pregnancy from 73 participants from the Atlanta AA Maternal-Child cohort. We measured eight urinary phthalate metabolites in early and late pregnancy, including Monoethyl phthalate (MEP), Mono(2-ethlyhexyl) phthalate (MEHP), and Mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), to assess maternal exposures to phthalates. Metabolite and metabolic pathway perturbation were evaluated using an untargeted HRM workflow. RESULTS: Geometric mean creatinine-adjusted levels of urinary MEP, MEHP, and MEHHP were 67.3, 1.4, and 4.1 µg/g creatinine, respectively, with MEP and MEHP higher than the mean levels of non-Hispanic blacks in the general US population (2015-2016). There were 73 and 1435 metabolic features significantly associated with at least one phthalate metabolite during early and late pregnancy (p < 0.005), respectively. Pathway enrichment analysis revealed perturbations in four inflammation- and oxidative-stress-related pathways associated with phthalate metabolite levels during both early and late pregnancy, including glycerophospholipid, urea cycle, arginine, and tyrosine metabolism. We confirmed 10 metabolites with level-1 evidence, which are associated with urinary phthalates, including thyroxine and thiamine, which were negatively associated with MEP, as well as tyramine and phenethylamine, which were positively associated with MEHP and MEHHP. CONCLUSION: Our results demonstrated that urinary phthalate levels were associated with perturbations in biological pathways connected with inflammation, oxidative stress, and endocrine disruption. The findings support future targeted investigations on molecular mechanisms underlying the impact of maternal phthalates exposure on adverse health outcomes.