Exploring autism spectrum disorder (ASD) and attention deficit disorder (ADD/ADHD) in children exposed to polybrominated biphenyl.

Background: Although the causes of attention-deficit/hyperactivity disorder (ADHD) and autism have not been identified, exposure to endocrine-disrupting chemicals, such as polybrominated biphenyl (PBB), during fetal development and early life has been suspected to impact neurological development. This study aims to investigate the association between prenatal and early life exposure to PBB and the development of ADHD and autism later in life. Methods: Data from the Michigan PBB Registry, a cohort of Michigan residents who had been exposed to PBB in a mass contamination event in 1973, was leveraged for this nested case-control analysis among two distinct samples: (1) Those who self-reported ADHD or autism diagnosis, and (2) mothers who reported their child's ADHD or autism diagnosis. PBB exposure was measured in participants of the PBB Registry, and the mother's PBB level was used in mother-reported analyses. Cases were matched with controls by sex and year of birth. Conditional logistic regression models were used to estimate the association between PBB level and case status. Results: PBB levels were higher among those who were exposed in early life compared with those exposed in utero (geometric mean: 0.300 ng/ml vs. 0.016 ng/ml). Among women in this cohort, a higher than expected proportion of self-reported ADHD diagnosis (11.11%), compared with population estimates. PBB was not associated with ADHD or autism in either self-reported or mother-reported analyses. Conclusions: This study adds to the sparse literature about prenatal and early life exposure to PBB-153 and ADHD and autism. Future studies should examine potential effect modification by sex.

Forecasting Hepatitis C Virus Status for Children in the United States: A Modeling Study.

BACKGROUND: Virtually all cases of hepatitis C virus (HCV) infection in children in the United States occur through vertical transmission, but it is unknown how many children are infected. Cases of maternal HCV infection have increased in the United States, which may increase the number of children vertically infected with HCV. Infection has long-term consequences for a child's health, but treatment options are now available for children ≥3 years old. Reducing HCV infections in adults could decrease HCV infections in children. METHODS: Using a stochastic compartmental model, we forecasted incidence of HCV infections in children in the United States from 2022 through 2027. The model considered vertical transmission to children <13 years old and horizontal transmission among individuals 13-49 years old. We obtained model parameters and initial conditions from the literature and the Centers for Disease Control and Prevention's 2021 Viral Hepatitis Surveillance Report. RESULTS: Model simulations assuming direct-acting antiviral treatment for children forecasted that the number of acutely infected children would decrease slightly and the number of chronically infected children would decrease even more. Alone, treatment and early screening in individuals 13-49 years old reduced the number of forecasted cases in children and, together, these policy interventions were even more effective. CONCLUSIONS: Based on our simulations, acute and chronic cases of HCV infection are remaining constant or slightly decreasing in the United States. Improving early screening and increasing access to treatment in adults may be an effective strategy for reducing the number of HCV infected children in the United States.

Former smoking associated with epigenetic modifications in human granulosa cells among women undergoing assisted reproduction.

Smoking exposure during adulthood can disrupt oocyte development in women, contributing to infertility and possibly adverse birth outcomes. Some of these effects may be reflected in epigenome profiles in granulosa cells (GCs) in human follicular fluid. We compared the epigenetic modifications throughout the genome in GCs from women who were former (N = 15) versus never smokers (N = 44) undergoing assisted reproductive technologies (ART). This study included 59 women undergoing ART. Smoking history including time since quitting was determined by questionnaire. GCs were collected during oocyte retrieval and DNA methylation (DNAm) levels were profiled using the Infinium MethylationEPIC BeadChip. We performed an epigenome-wide association study with robust linear models, regressing DNAm level at individual loci on smoking status, adjusting for age, ovarian stimulation protocol, and three surrogate variables. We performed differentially methylated regions (DMRs) analysis and over-representation analysis of the identified CpGs and corresponding gene set. 81 CpGs were differentially methylated among former smokers compared to never smokers (FDR < 0.05). We identified 2 significant DMRs (KCNQ1 and RHBDD2). The former smoking-associated genes were enriched in oxytocin signaling, adrenergic signaling in cardiomyocytes, platelet activation, axon guidance, and chemokine signaling pathway. These epigenetic variations have been associated with inflammatory responses, reproductive outcomes, cancer development, neurodevelopmental disorder, and cardiometabolic health. Secondarily, we examined the relationships between time since quitting and DNAm at significant CpGs. We observed three CpGs in negative associations with the length of quitting smoking (p < 0.05), which were cg04254052 (KCNIP1), cg22875371 (OGDHL), and cg27289628 (LOC148145), while one in positive association, which was cg13487862 (PLXNB1). As a pilot study, we demonstrated epigenetic modifications associated with former smoking in GCs. The study is informative to potential biological pathways underlying the documented association between smoking and female infertility and biomarker discovery for smoking-associated reproductive outcomes.

Neighborhood deprivation and racial differences in in vitro fertilization outcomes.

BACKGROUND: There are significant racial disparities in in vitro fertilization outcomes, which are poorly explained by individual-level characteristics. Environmental factors such as neighborhood-level socioeconomic factors may contribute to these disparities. However, few studies have directly addressed this research question in a large, racially diverse cohort. OBJECTIVE: This study aimed to investigate whether neighborhood deprivation is associated with differences in in vitro fertilization outcomes. STUDY DESIGN: Our retrospective cohort study included 1110 patients who underwent 2254 autologous in vitro fertilization cycles between 2014 and 2019 at an academic fertility center in the Southeastern United States. Neighborhood deprivation was estimated using the Neighborhood Deprivation Index, a composite variable measuring community levels of material capital based on poverty, occupation, housing, and education domains. Using multivariable log-binomial generalized estimating equations with cluster weighting, risk ratios and 95% confidence intervals were estimated for cycle cancellation, miscarriage (defined as spontaneous pregnancy loss before 20 weeks after a confirmed intrauterine gestation), and live birth according to patient Neighborhood Deprivation Index. RESULTS: There were positive associations between increasing Neighborhood Deprivation Index (indicating worsening neighborhood deprivation) and body mass index, as well as increasing prevalence of tubal and uterine factor infertility diagnoses. The crude probability of live birth per cycle was lower among Black (24%) than among White patients (32%), and the crude probability of miscarriage per clinical pregnancy was higher among Black (22%) than among White patients (12%). After adjustment, the Neighborhood Deprivation Index was not significantly associated with risk of cycle cancellation or live birth. Results were consistent when analyses were stratified by race. CONCLUSION: Our research demonstrates racial disparities between Black and White women in the incidence of miscarriage and live birth following in vitro fertilization. Although the level of neighborhood deprivation was closely related to race, it did not have strong associations with in vitro fertilization outcomes in our population as a whole or within strata of race.

In-utero exposure to polybrominated biphenyl (PBB) and menstrual cycle function in adulthood.

BACKGROUND: There is evidence that in-utero exposure to PBBs, and similar chemicals, are associated with several adverse reproductive health outcomes including altered pubertal timing. However, less is known about the effects of in-utero exposure to PBBs on menstrual cycle function and reproductive hormone levels in adulthood. METHODS: For this menstrual cycle study, we recruited reproductive-aged women in the Michigan PBB Registry who were not pregnant, lactating, or taking hormonal medications (2004-2014). A total of 41 women who were born after the PBB contamination incident (1973-1974) and were prenatally exposed to PBBs, were included in this analysis. We estimated in-utero PBB exposure using maternal serum PBB measurements taken after exposure and extrapolated to time of pregnancy using a PBB elimination model. Women were followed for up to 6 months during which they provided daily urine samples and completed daily diaries. The urine samples were assayed for estrone 3-glucuronide (E13G), pregnanediol 3-glucuronide (Pd3G), and follicle stimulating hormone (FSH). RESULTS: Women in our study were, on average, 27.5 (SD:5.3) years old and contributed 4.9 (SD:1.9) menstrual cycles of follow-up. Compared to women with low in-utero PBB exposure (≤1 ppb), women with medium (>1.0-3.0 ppb) and high (>3.0 ppb) exposure had higher maximum 3-day mean Pd3G levels during the luteal phase. Specifically, the age- and creatinine-adjusted maximum 3-day mean luteal phase Pd3G levels (95% CI) in increasing categories of in-utero PBB exposure were 9.2 (4.6,13.9), 14.8 (11.6,18.0), and 16.1 (12.9,19.3) µg/mg creatinine. There were no meaningful differences in average cycle length, follicular or luteal phase cycle length, bleed length, or creatinine-adjusted E13G or FSH levels by category of in-utero PBB exposure. CONCLUSION: Higher exposure to PBB in-utero was associated with increased progesterone levels across the luteal phase, however, most other menstrual cycle characteristics were largely unassociated with in-utero PBB exposure. Given our modest sample size, our results require cautious interpretation.

Maternal hepatitis C virus infection and three adverse maternal outcomes in the United States.

BACKGROUND: Hepatitis Virus C (HCV) infection rates have trended upwards among pregnant people in the USA since 2009. Existing evidence about HCV infections and maternal outcomes is limited; therefore, we used birth certificate data to investigate the association between HCV infection and maternal health outcomes. METHODS: We used the 2017 US birth certificate dataset (a cross-section of 1.4 million birth records) to assess the association between prevalent HCV infection and gestational diabetes, gestational hypertension, and eclampsia. Potential confounding variables included prenatal care, age, education, smoking, presence of sexually transmitted infections (STIs), body mass index (BMI), and weight gain during pregnancy. We restricted our analysis to only women with a first singleton pregnancy. Odds ratios were estimated by logistic regression models and separate models were tested for white and Black women. RESULTS: Only 0.31% of the women in our sample were infected with HCV (n = 4412). In an unadjusted model, we observed a modest significant protective association between HCV infection and gestational diabetes (Odds ratio [OR]: 0.83; 95% CI: 0.76-0.96); but this was attenuated with adjustment for confounding variables (Adjusted odds ratio [AOR]: 0.88; 95% CI: 0.76, 1.02). There was no association between HCV and gestational hypertension (AOR: 1.03; 95% CI: 0.91, 1.16) or eclampsia (AOR: 1.15; 95% CI: 0.69, 1.93). Results from the race stratified models were similar to the non-stratified summary models. CONCLUSION: We observed no statistically significant associations between maternal HCV infection with maternal health outcomes. Although, our analysis did indicate that HCV may lower the risk of gestational diabetes, this may be attributable to confounding. Studies utilizing more accurately measured HCV infection including those collecting type and timing of testing, and timing of infection are warranted to ensure HCV does not adversely impact maternal and/or fetal health. Particularly in the absence of recommended therapy for HCV during pregnancy.

Polybrominated biphenyls (PBBs) and prevalence of autoimmune disorders among members of the Michigan PBB registry.

BACKGROUND: Polybrominated biphenyls (PBBs), a class of endocrine disrupting chemicals, were the main chemicals present in one of the largest industrial accidents in the United States. We investigated the association between serum PBB-153 levels and autoimmune disorders among members of the Michigan PBB Registry. METHODS: Eight hundred and ninety-five members of the registry had both a serum PBB-153 measurement and had completed one or more questionnaires about autoimmune disorders. Autoimmune disorders were examined collectively and within specific organ systems. Sex-stratified unadjusted and adjusted log-binomial models were used to examine the association between tertiles of serum PBB-153 levels and autoimmune disorders. Models were adjusted by lifestage at exposure (in utero, childhood, adulthood), smoking history (never, past, current), and total serum lipid levels (continuous). We utilized cubic spline models to investigate non-linearity between serum PBB-153 levels and the prevalence of autoimmune disorders. RESULTS: Approximately 12.9% and 20.7% of male and female participants reported having one or more autoimmune disorders, respectively. After adjustment for potential confounders, we observed no association between PBB-153 tertiles and the composite classification of 'any autoimmune disorder' in either sex. We observed some evidence for an association between serum PBB-153 levels and rheumatoid arthritis in males and females; however, this was not statistically significant in females. We also observed some evidence for an association between serum PBB-153 levels and neurological- and thyroid-related autoimmune disorders in females, but again this was not statistically significant. Additionally, we identified dose-response curves for serum PBB-153 levels and the prevalence of autoimmune disorders that differed by lifestage of exposure and sex. CONCLUSIONS: We observed some evidence that increasing serum PBB-153 levels were associated with three specified autoimmune disorders. Studies focusing on these three autoimmune disorders and the potential non-linear trend differences by lifestage of exposure warrant further investigation.

Assessing Metabolic Differences Associated with Exposure to Polybrominated Biphenyl and Polychlorinated Biphenyls in the Michigan PBB Registry.

BACKGROUND: Polybrominated biphenyls (PBB) and polychlorinated biphenyls (PCB) are persistent organic pollutants with potential endocrine-disrupting effects linked to adverse health outcomes. OBJECTIVES: In this study, we utilize high-resolution metabolomics (HRM) to identify internal exposure and biological responses underlying PCB and multigenerational PBB exposure for participants enrolled in the Michigan PBB Registry. METHODS: HRM profiling was conducted on plasma samples collected from 2013 to 2014 from a subset of participants enrolled in the Michigan PBB Registry, including 369 directly exposed individuals (F0) who were alive when PBB mixtures were accidentally introduced into the food chain and 129 participants exposed to PBB in utero or through breastfeeding, if applicable (F1). Metabolome-wide association studies were performed for PBB-153 separately for each generation and ΣPCB (PCB-118, PCB-138, PCB-153, and PCB-180) in the two generations combined, as both had direct PCB exposure. Metabolite and metabolic pathway alterations were evaluated following a well-established untargeted HRM workflow. RESULTS: Mean levels were 1.75 ng/mL [standard deviation (SD): 13.9] for PBB-153 and 1.04 ng/mL (SD: 0.788) for ΣPCB. Sixty-two and 26 metabolic features were significantly associated with PBB-153 in F0 and F1 [false discovery rate (FDR) p<0.2], respectively. There were 2,861 features associated with ΣPCB (FDR p<0.2). Metabolic pathway enrichment analysis using a bioinformatics tool revealed perturbations associated with ΣPCB in numerous oxidative stress and inflammation pathways (e.g., carnitine shuttle, glycosphingolipid, and vitamin B9 metabolism). Metabolic perturbations associated with PBB-153 in F0 were related to oxidative stress (e.g., pentose phosphate and vitamin C metabolism) and in F1 were related to energy production (e.g., pyrimidine, amino sugars, and lysine metabolism). Using authentic chemical standards, we confirmed the chemical identity of 29 metabolites associated with ΣPCB levels (level 1 evidence). CONCLUSIONS: Our results demonstrate that serum PBB-153 is associated with alterations in inflammation and oxidative stress-related pathways, which differed when stratified by generation. We also found that ΣPCB was associated with the downregulation of important neurotransmitters, serotonin, and 4-aminobutanoate. These findings provide novel insights for future investigations of molecular mechanisms underlying PBB and PCB exposure on health. https://doi.org/10.1289/EHP12657.

Exposure to Particulate Matter Air Pollution and Age of Menarche in a Nationwide Cohort of U.S. Girls.

BACKGROUND: It remains unclear whether in utero and childhood exposure to air pollution affects pubertal development, particularly age of menarche in girls. OBJECTIVE: The aim of this study was to determine whether residential ambient particulate matter (PM) exposure in utero and during childhood is associated with age of menarche. METHODS: We studied 5,201 girls in the Growing Up Today Study 2 (2004-present) who were 10-17 y of age at enrollment (47.7% premenarchal; 52.3% postmenarchal). Exposure to three size fractions of PM [fine PM with aerodynamic diameter ≤2.5µm (PM2.5), PM with aerodynamic diameters between 2.5µm and 10µm (PM2.5-10), and PM with aerodynamic diameter 10µm (PM10)] was assigned based on maternal residential address, updated every 2 y, using nationwide spatiotemporal models. We estimated average PM exposure in utero, and time-varying windows: annual average exposure in the prior 1 and 2 y and cumulative average from birth. Age of menarche was self-reported on three surveys administered in 2004, 2006, and 2008. We calculated hazard ratios (HR) for menarche for an interquartile range (IQR) increase in PM exposure using Cox proportional hazard models adjusting for potential confounders. RESULTS: Girls attained menarche at 12.3 y of age on average. In the adjusted model, higher residential exposure to ambient PM2.5 during all time windows was associated with earlier age of menarche. The HRs of menarche for each IQR (4 µg/m3) increase in exposure to PM2.5 during the in utero period, 1 y prior to menarche, and throughout childhood were 1.03 [95% confidence interval (CI): 1.00, 1.06], 1.06 (95% CI: 1.02, 1.10) and 1.06 (95% CI: 1.02, 1.10), respectively. Effect estimates for PM10 exposure were similar, albeit attenuated, for all time windows. PM2.5-10 exposure was not associated with age of menarche. DISCUSSION: Among a large, nationwide, prospective cohort of U.S. girls, higher exposure to PM2.5 and PM10 in utero and throughout childhood was associated with an earlier age of menarche. Our results suggest that PM2.5 and PM10 may have endocrine-disrupting properties that could lead to altered timing of menarche. https://doi.org/10.1289/EHP12110.

Serum and follicular fluid metabolome and markers of ovarian stimulation.

STUDY QUESTION: What metabolic pathways and metabolites in the serum and follicular fluid are associated with peak estradiol levels and the number of mature oocytes? SUMMARY ANSWER: In the serum metabolome, mostly fatty acid and amino acid pathways were associated with estradiol levels and mature oocytes while in the follicular fluid metabolome, mostly lipid, vitamin, and hormone pathways were associated with peak estradiol levels and mature oocytes. WHAT IS KNOWN ALREADY: Metabolomics has identified several metabolic pathways and metabolites associated with infertility but limited data are available for ovarian stimulation outcomes. STUDY DESIGN, SIZE, DURATION: A prospective cohort study of women undergoing IVF from 2009 to 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 125 women undergoing a fresh IVF cycle at a fertility clinic in the Northeast United States who provided a serum and follicular fluid sample. Untargeted metabolomics profiling was conducted using liquid chromatography with high-resolution mass spectrometry in two chromatography columns (C18 and hydrophilic interaction chromatography (HILIC)). The main ovarian stimulation outcomes were peak serum estradiol levels and number of mature oocytes. We utilized adjusted generalized linear regression models to identify significant metabolic features. Models were adjusted for age,BMI, initial infertility diagnosis, and ovarian stimulation protocol. We then conducted pathway analysis using mummichog and metabolite annotation using level-1 evidence. MAIN RESULTS AND ROLE OF CHANCE: In the serum metabolome, 480 and 850 features were associated with peak estradiol levels in the C18 and HILIC columns, respectively. Additionally, 437 and 538 features were associated with mature oocytes in the C18 and HILIC columns, respectively. In the follicular fluid metabolome, 752 and 929 features were associated with peak estradiol levels in the C18 and HILIC columns, respectively, Additionally, 993 and 986 features were associated with mature oocytes in the C18 and HILIC columns, respectively. The most common pathways associated with peak estradiol included fatty acids (serum and follicular fluid), hormone (follicular fluid), and lipid pathways (follicular fluid). The most common pathways associated with the number of mature oocytes retrieved included amino acids (serum), fatty acids (serum and follicular fluid), hormone (follicular fluid), and vitamin pathways(follicular fluid). The vitamin D3 pathway had the strongest association with both ovarian stimulation outcomes in the follicularfluid. Four and nine metabolites were identified using level-1 evidence (validated identification) in the serum and follicular fluid metabolomes, respectively. LIMITATIONS, REASONS FOR CAUTION: Our sample was majority White and highly educated and may not be generalizable to thewider population. Additionally, residual confounding is possible and the flushing medium used in the follicular fluid could have diluted our results. WIDER IMPLICATIONS OF THE FINDINGS: The pathways and metabolites identified by our study provide novel insights into the biologicalmechanisms in the serum and follicular fluid that may underlie follicular and oocyte development, which could potentially be used to improve ovarian stimulation outcomes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the following grants from the National Institute of Environmental Health Sciences (P30-ES019776, R01-ES009718, R01-ES022955, P30-ES000002, R00-ES026648, and T32-ES012870), and National Institute of Diabetes and Digestive and Kidney Diseases (P30DK046200). The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.

Traffic-related air pollution and supplemental folic acid intake in relation to DNA methylation in granulosa cells.

BACKGROUND: Higher exposure to traffic-related air pollution (TRAP) is related to lower fertility, with specific adverse effects on the ovary. Folic acid may attenuate these effects. Our goal was to explore the relation of TRAP exposure and supplemental folic acid intake with epigenetic aging and CpG-specific DNA methylation (DNAm) in granulosa cells (GC). Our study included 61 women undergoing ovarian stimulation at a fertility center (2005-2015). DNAm levels were profiled in GC using the Infinium MethylationEPIC BeadChip. TRAP was defined using a spatiotemporal model to estimate residence-based nitrogen dioxide (NO2) exposure. Supplemental folic acid intake was measured with a validated food frequency questionnaire. We used linear regression to evaluate whether NO2 or supplemental folic acid was associated with epigenetic age acceleration according to the Pan-tissue, mural GC, and GrimAge clocks or DNAm across the genome adjusting for potential confounders and accounting for multiple testing with a false discovery rate < 0.1. RESULTS: There were no associations between NO2 or supplemental folic acid intake and epigenetic age acceleration of GC. NO2 and supplemental folic acid were associated with 9 and 11 differentially methylated CpG sites. Among these CpGs, only cg07287107 exhibited a significant interaction (p-value = 0.037). In women with low supplemental folic acid, high NO2 exposure was associated with 1.7% higher DNAm. There was no association between NO2 and DNAm in women with high supplemental folic acid. The genes annotated to the top 250 NO2-associated CpGs were enriched for carbohydrate and protein metabolism, postsynaptic potential and dendrite development, and membrane components and exocytosis. The genes annotated to the top 250 supplemental folic acid-associated CpGs were enriched for estrous cycle, learning, cognition, synaptic organization and transmission, and size and composition of neuronal cell bodies. CONCLUSIONS: We found no associations between NO2, supplemental folic acid, and DNAm age acceleration of GC. However, there were 20 differentially methylated CpGs and multiple enriched GO terms associated with both exposures suggesting that differences in GC DNAm could be a plausible mechanism underlying the effects of TRAP and supplemental folic acid on ovarian function.

Maternal Hepatitis C Virus Infection and Adverse Newborn Outcomes in the US.

OBJECTIVES: We investigated the relationship between maternal hepatitis C virus (HCV) infection and infant health. Furthermore, we evaluated racial disparities with these associations. METHODS: Using 2017 US birth certificate data, we investigated the association between maternal HCV infection and infant birthweight, preterm birth, and Apgar score. We used unadjusted and adjusted linear regression and logistic regression models. Models were adjusted for use of prenatal care, maternal age, maternal education, maternal smoking status, and the presence of other sexually transmitted infections. We stratified the models by race to describe the experiences of White and Black women separately. RESULTS: Maternal HCV infection was associated with reduced infant birthweight on average by 42.0 g (95% CI: -58.81, -25.30) for women of all races, 64.6 g (95% CI: -81.91, -47.26) for White women and 80.3 g (95% CI: -162.48, 1.93) for Black women. Women with maternal HCV infection had increased odds of having a preterm birth of 1.06 (95% CI: 0.96, 1.17) for women of all races, 1.06 (95% CI: 0.96, 1.18) for White women and 1.35 (95% CI: 0.93, 1.97) for Black women. Overall, women with maternal HCV infection had increased odds 1.26 (95% CI: 1.03, 1.55) of having a low/intermediate Apgar score; White and Black women with HCV infection had similarly increased odds of an infant with low/intermediate Apgar score in a stratified analysis: 1.23 (95% CI: 0.98, 1.53) for White women and 1.24 (95% CI: 0.51, 3.02) for Black women. CONCLUSIONS: Maternal HCV infection was associated with lower infant birthweight and higher odds of having a low/intermediate Apgar score. Given the potential for residual confounding, these results should be interpreted with caution.

Kentucky's abortion landscape, 2010 to 2019: an analysis of pre-Dobbs abortion disparities in a rural, restrictive state.

Background: Since 2010, many US states have passed laws restricting abortion providers' ability to provide care. Such legislation has no demonstrated health benefits and creates inequitable barriers for patients. Methods: To examine how Kentucky's abortion policies coincided with facility closures and abortion utilisation, we conducted a review of state abortion policies from 2010 to 2019 using newspapers and websites. We calculated abortion rates (abortions per 1000 women ages 15-44) by state of residence and provision for Kentucky, the South, and the US using data from the CDC and Kentucky Department of Health. We calculated percentages leaving and from out-of-state, and analysed abortions by race, pregnancy duration, and method. Findings: Of 17 policies passed between 2010 and 2019, ten were enacted, including 20-week and telemedicine bans. One of Kentucky's two abortion facilities closed in 2017. The pooled average abortion rate in Kentucky (4.1) and for Kentuckians (5.8) was lower than national averages (11.8 and 11.1). An average of 38% of Kentuckians left their state for care, compared to 7% nationally. In 2019, the abortion rate in Kentucky was 5.8 times higher for Black patients than White patients (compared to 4.8 times nationally). The majority (62%) of abortions in Kentucky took place at 7-13 weeks' gestation. Interpretation: Abortions in Kentucky were less frequent than in the South and US. The larger Black-White abortion rate gap reflects race- and class-based structural inequities in healthcare. Without federal protections, abortion access in Kentucky will continue waning. Funding: This study was supported by a philanthropic foundation that makes grants anonymously.

Elimination of PBB-153; findings from a cohort of Michigan adults.

BACKGROUND: An industrial accident led to the widespread contamination of polybrominated biphenyl (PBB), a flame retardant, into the food system in Michigan in the 1970's. PBB continues to be detected in Michiganders' blood some forty years later. It is necessary to understand the elimination rate and half-life of PBB because it may provide clues on how to hasten the elimination of it from the human body. METHODS: Serum samples were taken from young adult and adult participants of the Michigan PBB registry from 1974 to 2019. A single compartment model was assumed for the elimination rate for PBB-153 in young adults and adults (≥16 years). Generalized linear mixed models were used to estimate the average elimination rate of PBB-153 and allowed for a random intercept and slope for the time between measurements. Models were adjusted for age at exposure, body mass index (BMI) at initial measurement, and smoking. Models were also stratified by demographic characteristics. RESULTS: In total, 1974 participants contributed 4768 samples over a forty-year span. The median initial PBB-153 level was 1.542 parts per billion (ppb) (Range: 0.001-1442.48 ppb). The adjusted median participant-specific half-life for PBB-153 was 12.23 years. The half-life of PBB-153 was lengthened by higher initial PBB level (∼1.5 years), younger age at exposure (∼5.4 years), higher BMI (∼1.0 years), and increased gravidity (∼7.3 years). Additionally, the half-life of PBB-153 was shortened by smoking status (∼-2.8 years) and breastfeeding (∼-3.5 years). CONCLUSIONS: Consistent with previous studies, PBB-153 has been demonstrated to have a long half-life in the human body and may be modified by some demographic characteristics. These updated estimates of half-life will further support evaluation of health effects associated with PBB exposure. Investigations into mechanisms to accelerate elimination and reduce body burdens of PBB-153, especially those related to body weight, are needed.

Factors associated with never-use of long-acting reversible contraception among adult reproductive-aged women in Ohio.

BACKGROUND: The number of women using long-acting reversible contraception (LARC)-intrauterine devices (IUDs) and implants-is increasing and 14% of contraceptive users in the United States adopt LARC. We examined correlates of LARC never-use in a population-based survey of reproductive-aged women in Ohio. METHODS: We analyzed data from the 2018-19 Ohio Survey of Women. We examined the prevalence of LARC never-use and reasons for never-use among ever users of contraception (N = 2388). Using Poisson regression to generate prevalence ratios (PRs), we examined associations between selected correlates (demographic factors, healthcare access/quality measures, and religious/political views) and LARC never-use. RESULTS: Most Ohio women (74%) had never used LARC. Commonly reported reasons for not using an IUD or an implant were preferring a different method (46% and 45%, respectively), not wanting an object inside their body (45% and 43%), side effect concerns (39% and 33%), insertion/removal concerns (31% and 25%), and unfamiliarity (13% and 20%). Conservative political views (PR: 1.12, 95% confidence interval [CI]: 1.04-1.22), pro-life affiliation (PR: 1.11, 95% CI: 1.02-1.20), placing high importance on religion in daily life (PR: 1.15, 95% CI: 1.06-1.26), and being non-Hispanic white as compared to non-Hispanic Black (PR: 1.20, 95% CI: 1.02-1.41) were significantly associated with LARC never-use. Findings were generally similar for models analyzing IUD and implant never-use separately. CONCLUSIONS: Among ever-users of contraception, LARC never-use was associated with having conservative political views, being religious, and having a pro-life affiliation. Except for race/ethnicity, demographic and healthcare measures were not associated with LARC never-use among women in Ohio.

Using follicular fluid metabolomics to investigate the association between air pollution and oocyte quality.

BACKGROUND AND AIM: Our objective was to use metabolomics in a toxicological-relevant target tissue to gain insight into the biological processes that may underlie the negative association between air pollution exposure and oocyte quality. METHODS: Our study included 125 women undergoing in vitro fertilization at an academic fertility center in Massachusetts, US (2005-2015). A follicular fluid sample was collected during oocyte retrieval and untargeted metabolic profiling was conducted using liquid chromatography with ultra-high-resolution mass spectrometry and two chromatography columns (C18 and HILIC). Daily exposure to nitrogen dioxide (NO2), ozone, fine particulate matter, and black carbon was estimated at the women's residence using spatiotemporal models and averaged over the period of ovarian stimulation (2-weeks). Multivariable linear regression models were used to evaluate the associations between the air pollutants, number of mature oocytes, and metabolic feature intensities. A meet-in-the-middle approach was used to identify overlapping features and metabolic pathways. RESULTS: Of the air pollutants, NO2 exposure had the largest number of overlapping metabolites (C18: 105; HILIC: 91) and biological pathways (C18: 3; HILIC: 6) with number of mature oocytes. Key pathways of overlap included vitamin D3 metabolism (both columns), bile acid biosynthesis (both columns), C21-steroid hormone metabolism (HILIC), androgen and estrogen metabolism (HILIC), vitamin A metabolism (HILIC), carnitine shuttle (HILIC), and prostaglandin formation (C18). Three overlapping metabolites were confirmed with level-1 or level-2 evidence. For example, hypoxanthine, a metabolite that protects against oxidant-induced cell injury, was positively associated with NO2 exposure and negatively associated with number of mature oocytes. Minimal overlap was observed between the other pollutants and the number of mature oocytes. CONCLUSIONS: Higher exposure to NO2 during ovarian stimulation was associated with many metabolites and biologic pathways involved in endogenous vitamin metabolism, hormone synthesis, and oxidative stress that may mediate the observed associations with lower oocyte quality.

Housing Stability and Access to General Healthcare and Reproductive Healthcare Among Women in Ohio.

BACKGROUND: The relationship between housing instability and reproductive healthcare is understudied. We examined the association between housing insecurity and access and utilization of general healthcare, contraceptive healthcare, and abortion care. METHODS: Using data from a population-representative survey of adult reproductive-age Ohio women (N = 2,529), we assessed housing insecurity (not paying rent/mortgage on time in the past year). We examined associations between housing insecurity and the following outcomes: (1) not being able to access general healthcare in the past year; (2) experiencing delays or difficulties in accessing contraceptive healthcare in the past year; and (3) ever having an abortion. We used unadjusted and adjusted logistic regression models. We selected confounders a priori and included age, socioeconomic status, and healthcare status. RESULTS: Overall, 10.6% of Ohio women of adult reproductive age experienced housing insecurity. Approximately 27.5% of respondents were not able to access general healthcare and 10.4% experienced delays or difficulties in accessing contraceptive care. Compared to housing-secure respondents, housing-insecure women were less able to access general healthcare (adjusted odds ratio [aOR]:2.16; 95% confidence interval [CI]:1.45-3.23) and more likely to experience delays or difficulties when accessing contraceptive care (aOR:1.74; 95% CI:1.00-3.04). Insecure housing was not statistically associated with ever having an abortion (aOR:1.76; 95% CI:0.93-3.34). CONCLUSIONS: In this study, recent housing insecurity was associated with poorer access to general and contraceptive healthcare. Studies utilizing multidimensional measures of housing insecurity and other material insecurity measures are needed to further explore the relationship between material insecurity and access to general and contraceptive care.

Community-based Systems Dynamics for Reproductive Health: An Example from Urban Ohio.

BACKGROUND: Health outcomes, risk factors, and policies are complexly related to the reproductive health system. Systems-level frameworks for understanding and acting within communities through community-engaged research are needed to mitigate adverse reproductive health outcomes more effectively within the community. OBJECTIVES: To describe and share lessons learned from an ongoing application of a participatory modeling approach (community-based system dynamics) that aims to eliminate racial inequities in Black-White reproductive health outcomes. METHODS: The community-based system dynamics approach involves conducting complementary activities, workshops, modeling, and dissemination. We organized workshops, co-developed a causal loop diagram of the reproductive health system with participants from the community, and created materials to disseminate workshop findings and preliminary models. LESSONS LEARNED: Many opportunities exist for cross-fertilization of best practices between community-based system dynamics and community-based participatory research. Shared learning environments offer benefits for modelers and domain experts alike. Additionally, identifying local champions from the community helps manage group dynamics. CONCLUSIONS: Community-based system dynamics is well-suited for understanding complexity in the reproductive health system. It allows participants from diverse perspectives to identify strategies to eliminate racial inequities in reproductive health outcomes.

Characterizing the follicular fluid metabolome: quantifying the correlation across follicles and differences with the serum metabolome.

OBJECTIVE: To compare the variability in metabolomes between the serum and follicular fluid, as well as across 3 dominant follicles. DESIGN: Prospective cohort study. SETTING: An academic fertility clinic in the northeastern United States, 2005-2015. PATIENTS: One hundred thirty-five women undergoing in vitro fertilization treatment who provided a serum sample during ovarian stimulation and up to 3 follicular fluid samples during oocyte retrieval. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Samples were analyzed using liquid chromatography with high-resolution mass spectrometry and 2 chromatography columns (C18 hydrophobic negative and hydrophilic interaction chromatography [HILIC] positive). We calculated overall, feature-specific, and subject-specific correlation coefficients to describe how strongly the intensity of overlapping metabolic features were associated between the serum and follicular fluid and between the 1st-2nd, 1st-3rd, and 2nd-3rd follicles. Feature-specific correlations were adjusted for age, body mass index, infertility diagnosis, ovarian stimulation protocol, and year. RESULT(S): From the C18-negative column and the high-resolution mass spectrometry, 7,830 serum features and 10,790 follicular fluid features were detected in ≥20% of samples. After screening retention times and checking for 1:1 matching, 1,928 features overlapped between the 2 metabolomes. From the HILIC-positive column and the high-resolution mass spectrometry, after applying the same exclusion criteria, there were 9,074 serum features, 5,542 follicular fluid features, and 1,149 features that overlapped. When comparing the feature intensity of overlapping metabolites in the serum and the follicular fluid, the overall (C18, 0.45; HILIC, 0.63), median feature-specific (C18, 0.35; HILIC, 0.37), and median subject-specific (C18, 0.42; HILIC, 0.59) correlations were low to moderate. In contrast, among the overlapping features across all 3 follicles, the overall (C18, all 0.99; HILIC, all 0.99), median feature-specific (C18, 0.74-0.81; HILIC, 0.79-0.85), and median subject-specific (C18, 0.88-0.89; HILIC, 0.90-0.91) correlations between follicular fluid metabolomics features within a woman were high. CONCLUSION(S): We observed minimal overlap and weak-to-moderate correlation between metabolomic features in the serum and follicular fluid but a large overlap and strong correlation between metabolomic features across follicles within a woman. The follicular fluid appears to represent a novel matrix, distinct from serum, which may be a rich source of biologic predictors of female fertility and reproductive outcomes.

Comparison of abortion incidence estimates derived from direct survey questions versus the list experiment among women in Ohio.

Abortion is highly stigmatized in the United States which prevents its accurate measurement in surveys. The list experiment aims to improve the reporting of abortion history. We evaluated whether a list experiment resulted in higher reporting of abortion experiences than did two direct questions. Utilizing data from a representative survey of adult women of reproductive age in Ohio, we examined abortion history using two direct questions and a double list experiment. Through the double list experiment, we asked respondents to report how many of two lists of health items they had experienced; one list included abortion. We compared weighted history of abortion between these measures and by respondent demographic characteristics (age and socioeconomic status). Estimates of abortion history were similar between direct and list experiment questions. When measured with the two different direct question of abortion history, 8.4% and 8.0% of all respondents indicated ever having an abortion and with the list experiment, 8.5% indicated ever having an abortion. In a Midwestern state-level survey, the list experiment did not lead to increases in abortion reporting as compared to the direct questions. Subgroup analyses require larger samples, and future iterations should incorporate related but non-stigmatized control items to reduce misclassification and under-powering of such subgroup analyses.