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.

Epigenetic age acceleration in follicular fluid and markers of ovarian response among women undergoing IVF.

STUDY QUESTION: Are markers of epigenetic age acceleration in follicular fluid associated with outcomes of ovarian stimulation? SUMMARY ANSWER: Increased epigenetic age acceleration of follicular fluid using the Horvath clock, but not other epigenetic clocks (GrimAge and Granulosa Cell), was associated with lower peak estradiol levels and decreased number of total and mature oocytes. WHAT IS KNOWN ALREADY: In granulosa cells, there are inconsistent findings between epigenetic age acceleration and ovarian response outcomes. STUDY DESIGN, SIZE, DURATION: Our study included 61 women undergoing IVF at an academic fertility clinic in the New England area who were part of the Environment and Reproductive Health Study (2006-2016). PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants provided a follicular fluid sample during oocyte retrieval. DNA methylation of follicular fluid was assessed using a genome-wide methylation screening tool. Three established epigenetic clocks (Horvath, GrimAge, and Granulosa Cell) were used to predict DNA-methylation-based epigenetic age. To calculate the age acceleration, we regressed epigenetic age on chronological age and extracted the residuals. The association between epigenetic age acceleration and ovarian response outcomes (peak estradiol levels, follicle stimulation hormone, number of total, and mature oocytes) was assessed using linear and Poisson regression adjusted for chronological age, three surrogate variables (to account for cellular heterogeneity), race, smoking status, initial infertility diagnosis, and stimulation protocol. MAIN RESULTS AND ROLE OF CHANCE: Compared to the median chronological age of our participants (34 years), the Horvath clock predicted, on an average, a younger epigenetic age (median: 24.2 years) while the GrimAge (median: 38.6 years) and Granulosa Cell (median: 39.0 years) clocks predicted, on an average, an older epigenetic age. Age acceleration based on the Horvath clock was associated with lower peak estradiol levels (-819.4 unit decrease in peak estradiol levels per standard deviation increase; 95% CI: -1265.7, -373.1) and fewer total (% change in total oocytes retrieved per standard deviation increase: -21.8%; 95% CI: -37.1%, -2.8%) and mature oocytes retrieved (% change in mature oocytes retrieved per standard deviation increase: -23.8%; 95% CI: -39.9%, -3.4%). The age acceleration based on the two other epigenetic clocks was not associated with markers of ovarian response. LIMITATIONS, REASONS FOR CAUTION: Our sample size was small and we did not specifically isolate granulosa cells from follicular fluid samples so our samples could have included mixed cell types. WIDER IMPLICATIONS OF THE FINDINGS: Our results highlight that certain epigenetic clocks may be predictive of ovarian stimulation outcomes when applied to follicular fluid; however, the inconsistent findings for specific clocks across studies indicate a need for further research to better understand the clinical utility of epigenetic clocks to improve IVF treatment. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by grants ES009718, ES022955, ES000002, and ES026648 from the National Institute of Environmental Health Sciences (NIEHS) and a pilot grant from the NIEHS-funded HERCULES Center at Emory University (P30 ES019776). RBH was supported by the Emory University NIH Training Grant (T32-ES012870). TRIAL REGISTRATION NUMBER: N/A.

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.

The associations between pre-conception urinary phthalate concentrations, the serum metabolome, and live birth among women undergoing assisted reproduction.

BACKGROUND: Phthalates are ubiquitous endocrine disruptors. Past studies have shown an association between higher preconception urinary concentrations of phthalate metabolites and lower fertility in women; however, the biological mechanisms remain unclear. Our exploratory study aimed to understand the metabolites and pathways associated with maternal preconception phthalate exposure and examine if any may underline the association between phthalate exposure and live birth using untargeted metabolomics. METHODS: Participants (n = 183) were part of the Environment and Reproductive Health (EARTH) study, a prospective cohort that followed women undergoing in vitro fertilization (IVF) at the Massachusetts General Hospital Fertility Center (2005-2016). On the same day, women provided a serum sample during controlled ovarian stimulation, which was analyzed for metabolomics using liquid chromatography coupled with high-resolution mass spectrometry and two chromatography columns, and a urine sample, which was analyzed for 11 phthalate metabolites using targeted approaches. We used multivariable generalized linear models to identified metabolic features associated with urinary phthalate metabolite concentrations and live birth, followed by enriched pathway analysis. We then used a meet-in-the-middle approach to identify overlapping pathways and features. RESULTS: Metabolic pathway enrichment analysis revealed 43 pathways in the C18 negative and 32 pathways in the HILIC positive columns that were significantly associated (p < 0.05) with at least one of the 11 urinary phthalate metabolites or molar sum of di-2-ethylhexyl phthalate metabolites. Lipid, amino acid, and carbohydrate metabolism were the most common pathways associated with phthalate exposure. Five pathways, tryptophan metabolism, tyrosine metabolism, biopterin metabolism, carnitine shuttle, and vitamin B6 metabolism, were also identified as being associated with at least one phthalate metabolite and live birth following IVF. CONCLUSION: Our study provides further insight into the metabolites and metabolomics pathways, including amino acid, lipid, and vitamin metabolism that may underlie the observed associations between phthalate exposures and lower fertility in women.

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.

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.

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.

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.

Evaluation of the Use of Saliva Metabolome as a Surrogate of Blood Metabolome in Assessing Internal Exposures to Traffic-Related Air Pollution.

In the omics era, saliva, a filtrate of blood, may serve as an alternative, noninvasive biospecimen to blood, although its use for specific metabolomic applications has not been fully evaluated. We demonstrated that the saliva metabolome may provide sensitive measures of traffic-related air pollution (TRAP) and associated biological responses via high-resolution, longitudinal metabolomics profiling. We collected 167 pairs of saliva and plasma samples from a cohort of 53 college student participants and measured corresponding indoor and outdoor concentrations of six air pollutants for the dormitories where the students lived. Grand correlation between common metabolic features in saliva and plasma was moderate to high, indicating a relatively consistent association between saliva and blood metabolites across subjects. Although saliva was less associated with TRAP compared to plasma, 25 biological pathways associated with TRAP were detected via saliva and accounted for 69% of those detected via plasma. Given the slightly higher feature reproducibility found in saliva, these findings provide some indication that the saliva metabolome offers a sensitive and practical alternative to blood for characterizing individual biological responses to environmental exposures.

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.

The influence of fine particulate matter on the association between residential greenness and ovarian reserve.

BACKGROUND: Natural vegetation, or greenness, is thought to improve health through its ability to buffer and reduce harmful environmental exposures as well as relieve stress, promote physical activity, restore attention, and increase social cohesion. In concert, these effects could help mitigate the detrimental effects of air pollution on reproductive aging in women. METHODS: Our analysis included 565 women attending the Massachusetts General Hospital Fertility Center (2004-2014) who had a measured antral follicle count (AFC), a marker of ovarian reserve. We calculated peak residential greenness in the year prior to AFC using 250 m2 normalized difference vegetation index (NDVI) from the Terra and Aqua satellites operated by the United States National Aeronautics and Space Administration. Validated spatiotemporal models estimated daily residential exposure to particulate matter <2.5 µm (PM2.5) for the 3 months prior to AFC. Poisson regression models with robust standard errors were used to estimate the association between peak greenness, average PM2.5 exposure, and AFC adjusted for age, BMI, smoking status, education, year, and season. RESULTS: Women in our study had a mean age of 35.2 years with a standard deviation (SD) of 4.3 years (min: 20 years, max: 45 years). The peak residential NDVI ranged from 0.07 to 0.92 with a SD of 0.18. There was no statistically significant association between peak residential greenness and AFC; however, higher exposure to PM2.5 was associated with lower AFC (-6.2% per 2 µg/m3 [1 SD increase] 95% CI -11.8, -0.3). There was a significant interaction between exposure to PM2.5 and peak greenness on AFC (P-interaction: 0.03). Among women with an average PM2.5 exposure of 7 µg/m3, a SD increase in residential peak greenness was associated with a 5.6% (95% CI -0.4, 12.0) higher AFC. Conversely, among women with a PM2.5 exposure of 12 µg/m3, a SD increase in residential peak greenness was associated with a 5.8% (95% CI -13.1, 2.1) lower AFC. CONCLUSIONS: Residing in an area with high levels of greenness may slow reproductive aging in women only when exposure to PM2.5 is low.

For Human Papillomavirus Self-Sampling, Stated Willingness Does Not Correspond With Subsequent Uptake by Rural Malawian Women.

BACKGROUND: Human papilloma virus (HPV), the causative agent for cervical cancer, can be tested for using self-collected vaginal samples. Self-collection is promising for HPV screening in hard-to-reach populations. To assess the relationship between willingness to self-collect and subsequent uptake of self-collection, we conducted a longitudinal study of reproductive-age women in rural Malawi. METHODS: At baseline, we asked women if they would be willing to self-collect a vaginal sample for HPV testing. At follow-up (12-18 months later), we offered the same women the opportunity to self-collect a sample for HPV testing. We examined unadjusted and adjusted associations between baseline willingness to self-collect a sample for HPV testing and uptake of self-collection at follow-up using log-binomial models. RESULTS: Among 122 women who, at baseline, indicated willingness to self-collect, n = 65 (53%) agreed to self-collect a sample at follow-up. Of 64 women who stated unwillingness at baseline to self-collect, n = 30 (47%) self-collected a sample for testing at follow-up. We observed no association between women's willingness at baseline and their observed self-collection decision at follow-up (unadjusted prevalence ratio, 1.14; 95% confidence interval, 0.83-1.55). The association remained null after adjustment for age, awareness of cervical cancer, and perceived behavioral control. CONCLUSIONS: Our results suggest that evaluation of acceptability of self-collection should go beyond simply asking women if they would be willing to self-collect a vaginal sample. Given that half of this study's participants agreed to self-collect a sample when the opportunity was offered, regardless of their previously stated preferences, self-collection should be offered to everyone.

An Assessment of Risk Factors for Herpes Simplex Virus Type 2 Infection in Malawian Women Using 2 Classifications for the HerpeSelect 2 Test.

BACKGROUND: The HerpeSelect 2 ELISA IgG test for herpes simplex virus type 2 (HSV-2) infection is widely used, convenient, and inexpensive. However, it has been shown to have lower specificity among populations in Sub-Saharan Africa compared with HSV-2 tests regarded as criterion standards. METHODS: In 2016, we collected blood and survey data from 248 women participating in a community-based cohort study in rural Malawi (the Umoyo wa Thanzi project). Using multinomial logistic regression accounting for village-level clustering, we examined unadjusted associations between select demographic and sexual risk factors and HSV-2 serostatus. Because increasing the index value cutpoint for a positive result improves specificity, we coded HSV-2 serostatus in 2 ways: the manufacturer's recommended cutpoints (<0.9, negative; 0.9-1.1, indeterminate; >1.1, positive) and modified cutpoints with improved specificity (<0.9, negative; 0.9-3.5, indeterminate; >3.5, positive). We aimed to investigate whether associations between select risk factors and HSV-2 serostatus varied under the 2 approaches. RESULTS: The prevalence of HSV-2 in this sample was 67% under the manufacturer's cutpoint and 22% under the modified cutpoint. Under both cutpoints, age, household size, number of marriages, and number of pregnancies were associated with HSV-2-positive serostatus. Using modified cutpoints, current bacterial vaginosis (odds ratio [OR], 3.17; 95% confidence interval [CI], 1.35-7.47), partner concurrency (OR, 4.88; 95% CI, 2.54-9.37) and unsure about partner concurrency (OR, 1.91; 95% CI, 1.08-3.38) were associated with HSV-2 seropositivity. Household size, education, and marital status were the only variables significantly associated with indeterminate HSV-2 serostatus using the modified cutpoints. CONCLUSION: HSV-2-focused interventions informed by identifying individuals likely to have or acquire HSV-2 must be aware that different target populations may emerge depending on which cutpoints are adopted.

Abortion Access in Ohio's Changing Legislative Context, 2010-2018.

Objectives. To examine abortion utilization in Ohio from 2010 to 2018, a period when more than 15 abortion-related laws became effective.Methods. We evaluated changes in abortion rates and ratios examining gestation, geographic distribution, and abortion method in Ohio from 2010 to 2018. We used data from Ohio's Office of Vital Statistics, the Centers for Disease Control and Prevention's Abortion Surveillance Reports, the American Community Survey, and Ohio's Public Health Data Warehouse.Results. During 2010 through 2018, abortion rates declined similarly in Ohio, the Midwest, and the United States. In Ohio, the proportion of early first trimester abortions decreased; the proportion of abortions increased in nearly every later gestation category. Abortion ratios decreased sharply in most rural counties. When clinics closed, abortion ratios dropped in nearby counties.Conclusions. More Ohioans had abortions later in the first trimester, compared with national patterns, suggesting delays to care. Steeper decreases in abortion ratios in rural versus urban counties suggest geographic inequity in abortion access.Public Health Implications. Policies restricting abortion access in Ohio co-occur with delays to care and increasing geographic inequities. Restrictive policies do not improve reproductive health.

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.

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.

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.

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.

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.

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.