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Background: Fibroids (hormonally responsive benign tumors) often undergo volume changes in pregnancy. Because per- and polyfluoroalkyl substances (PFAS) disrupt hormonal signaling, they might affect fibroid growth. We assessed associations between PFAS and fibroid changes in pregnancy. Methods: We analyzed seven PFAS, including perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), in plasma collected at 10-13 wk gestation from 2,621 women in the NICHD Fetal Growth Studies Singletons cohort (2009-2013). Sonographers recorded fibroid number and volume of the three largest fibroids during up to six timed ultrasounds. Generalized linear models assessed associations of baseline [log.sub.2]-transformed PFAS and fibroid number, volume, and presence, and weighted quantile sum regression evaluated the PFAS mixture. Generalized linear mixed models with random intercepts assessed associations of PFAS and longitudinal fibroid number and total volume. Volume analyses were stratified by total volume at first visualization [equivalent to a fibroid Results: Fibroid prevalence was 9.4% (n = 245 women). PFAS were not associated with changes in fibroid number, but were associated with volume trajectory, depending on baseline volume. Among women with small volume, PFAS were associated with fibroid growth: Each doubling in PFHxS and PFOS concentrations was associated with 3.6% [95% confidence interval (CI): 0.2, 7.0 and 5.2% (95% CI: -0.4, 11.1)] greater weekly fibroid growth, respectively. Among women with medium volume, PFAS were associated with shrinking: Doublings in PFOS, PFDA, and PFUnDA concentrations were associated with 1.9% (95% CI: 0.4, 3.3), 1.2% (95% CI: 0.1, 2.4), and 1.6% (95% CI: 0.4, 2.8) greater weekly fibroid volume reduction, respectively. Discussion: Certain PFAS were associated with fibroid growth among women with small fibroids and decreases among women with medium fibroids. PFAS were not associated with fibroid prevalence or number; therefore, PFAS may influence prevalent fibroids rather than initiating fibroid development. https://doi.org/10.1289/EHP11606, Introduction Uterine leiomyoma (fibroids) are benign gynecologic tumors that can cause pain and heavy bleeding. (1) Prevalence increases with age among premenopausal women and is highest in non-Hispanic Black and [...]

Background: Identifying the impact of environmental mixtures on human health is an important topic. However, such studies face challenges when exposure measurements lie below limit of detection (LOD). While various approaches for accommodating a single exposure subject to LOD have been used, their impact on mixture analysis has not been thoroughly investigated. Our study aims to understand the impact of five popular LOD accommodation approaches on mixture analysis results with multiple exposures subject to LOD, including omitting subjects with any exposures below LOD (complete case analysis); single imputations by LOD/ 2 , and by estimates from a censored accelerated failure time (AFT) model; and multiple imputation (MI) with or without truncation based on LOD. Methods: In extensive simulation studies with high-dimensional and highly correlated exposures and a continuous health outcome, we examined the performance of each LOD approach on three mixture analysis methods: elastic net regression, weighted quantile sum regression (WQS) and Bayesian kernel machine regression (BKMR). We further analyzed data from the National Health and Nutrition Examination Survey (NHANES) on how persistent organic pollutants (POPs) influenced leukocyte telomere length (LTL). Results: Complete case analysis was inefficient and could result in severe bias for some mixture methods. Imputation by LOD/ 2 showed unstable performance across mixture methods. Conventional MI was associated with consistent mild biases, which can be reduced by using a truncated distribution for imputation. Estimating censored values by AFT models had a minimal impact on the results. In the NHANES analysis, imputation by LOD/ 2 , truncated MI and censored AFT models performed similarly, with a positive overall effect of POPs on LTL while PCB126, PCB169 and furan 2,3,4,7,8-pncdf being the most important exposures. Conclusions: Our study favored using truncated MI and censored AFT models to accommodate values below LOD for the stability of downstream mixture analysis. [ABSTRACT FROM AUTHOR]

Background: Multifetal gestation could be associated with higher long‐term maternal mortality because it increases the risk of pregnancy complications such as preeclampsia and preterm birth, which are in turn linked to postpartum cardiovascular risk. Objectives: We examined whether spontaneously conceived multifetal versus singleton gestation was associated with long‐term maternal mortality in a racially diverse U.S. cohort. Methods: We ascertained vital status as of 2016 via linkage to the National Death Index and Social Security Death Master File of 44,174 mothers from the Collaborative Perinatal Project (CPP; 1959–1966). Cox proportional hazards models with maternal age as the time scale assessed associations between history of spontaneous multifetal gestation (in the last CPP observed pregnancy or prior pregnancy) and all‐cause and cardiovascular mortality, adjusted for demographics, smoking status, and preexisting medical conditions. We calculated hazard ratios (HR) for all‐cause and cause‐specific mortality over the study period and until age 50, 60, and 70 years (premature mortality). Results: Of eligible participants, 1672 (3.8%) had a history of multifetal gestation. Participants with versus without a history of multifetal gestation were older, more likely to have a preexisting condition, and more likely to smoke. By 2016, 51% of participants with and 38% of participants without a history of multifetal gestation had died (unadjusted all‐cause HR 1.14, 95% confidence interval [CI] 1.07, 1.23). After adjustment for smoking and preexisting conditions, a history of multifetal gestation was not associated with all‐cause (adjusted HR 1.00, 95% CI 0.93, 1.08) or cardiovascular mortality (adjusted HR 0.99, 95% CI 0.87, 1.11) over the study period. However, history of multifetal gestation was associated with an 11% lower risk of premature all‐cause mortality (adjusted HR 0.89, 95% CI 0.82, 0.96). Conclusions: In a cohort with over 50 years of follow‐up, history of multifetal gestation was not associated with all‐cause mortality, but may be associated with a lower risk of premature mortality. [ABSTRACT FROM AUTHOR]

Background: Longitudinal studies show that lower cognitive performance in adolescence and early adulthood is associated with higher risk of suicide death throughout adulthood. However, it is unclear whether this cognitive vulnerability originates earlier in childhood since studies conducted in children are scarce and have inconsistent results. Methods: Vital status of 49,853 individuals born between 1959 and 1966 to participants in the Collaborative Perinatal Project cohort was determined by a probabilistic linkage to the National Death Index, covering all US deaths occurring from 1979 through 2016. Cox proportional hazard models were used to examine associations of general, verbal, and non‐verbal intelligence at ages 4 and 7, and academic skills at age 7 with suicide death coded according to ICD‐9/10 criteria, while accounting for sociodemographic and pregnancy factors previously associated with suicide in this sample. Results: By the end of 2016, 288 cohort members had died by suicide. Cognitive performance at 7 years on tests with verbal components was associated with suicide risk (average vs. high verbal intelligence, HR = 1.97, 95% CI 1.05–3.71; low vs. high spelling skills, HR = 2.02, 95% CI 1.16–3.51; low vs. high reading skills, HR = 2.01, 95% CI 1.27–3.17). Associations were still evident, especially for verbal intelligence and reading skills, but hazard ratios were attenuated after adjusting for prenatal and sociodemographic factors at birth (verbal intelligence, HR = 1.97, 95% CI 1.03–3.78; spelling, HR = 1.61, 95% CI 0.90–2.88; reading, HR = 1.67, 95% CI 1.02–2.72). Conclusions: Childhood neurocognitive performance is associated with vulnerability to suicide mortality through middle‐adulthood, suggesting that there might be a cognitive diathesis for suicide originating in early childhood. Future studies should examine how multiple domains of childhood cognitive performance contribute to vulnerability to suicide risk, including by increasing risk for social and environmental factors that are associated not only with suicide but also with many types of psychiatric disorders. [ABSTRACT FROM AUTHOR]

Understanding the association between mixtures of environmental toxicants and time‐to‐pregnancy (TTP) is an important scientific question as sufficient evidence has emerged about the impact of individual toxicants on reproductive health and that individuals are exposed to a whole host of toxicants rather than an individual toxicant. Assessing mixtures of chemical effects on TTP poses significant statistical challenges, namely (i) TTP being a discrete survival outcome, typically subject to left truncation and right censoring, (ii) chemical exposures being strongly correlated, (iii) appropriate transformation to account for some lipid‐binding chemicals, (iv) non‐linear effects of some chemicals, and (v) high percentage of concentration below the limit of detection (LOD) for some chemicals. We propose a discrete frailty modeling framework (named Discnet) that allows selection of correlated covariates while appropriately addressing the methodological issues mentioned above. Discnet is shown to have better and stable false negative and false positive rates compared to alternative methods in various simulation settings. We did a detailed analysis of the pre‐conception endocrine disrupting chemicals and TTP from the LIFE study and found that older females, female exposure to cotinine (smoking), DDT conferred a delay in getting pregnant, which was consistent across various approaches to account for LOD as well as non‐linear associations. [ABSTRACT FROM AUTHOR]

Background: The association between obesity (body mass index (BMI) 30 kg/m² ) and pattern of medication use during pregnancy in the United States is not well-studied. Higher pre-pregnancy BMI may be associated with increases or decreases in medication use across pregnancy as symptoms (e.g. reflux) or comorbidities (e.g. gestational diabetes) requiring treatment that may be associated with higher BMI could also change with advancing gestation. Objectives: To determine whether prenatal medication use, by the number and types of medications, varies by pre-pregnancy obesity status. Methods: In a secondary data analysis of a racially/ethnically diverse prospective cohort of pregnant women with low risk for fetal abnormalities enrolled in the first trimester of pregnancy and followed to delivery (singleton, 12 United States clinical sites), free text medication data were obtained at enrollment and up to five follow-up visits and abstracted from medical records at delivery. Results: In 436 women with obesity and 1750 women without obesity (pre-pregnancy BMI, 19–29.9 kg/m² ), more than 70% of pregnant women (77% of women with and 73% of women without obesity) reported taking at least one medication during pregnancy, respectively (adjusted risk ratio (aRR)=1.10, 95% confidence interval (CI)=1.01, 1.20), with 81% reporting two and 69% reporting three or more. A total of 17 classes of medications were identified. Among medication classes consumed by at least 5% of all women, the only class that differed between women with and without obesity was hormones and synthetic substitutes (including steroids, progesterone, diabetes, and thyroid medications) in which women with obesity took more medications (11 vs. 5%, aRR = 1.9, 95% CI = 1.38, 2.61) compared to women without obesity. Within this class, a higher percentage of women with obesity took diabetes medications (2.3 vs. 0.7%) and progesterone (3.4 vs. 1.3%) than their non-obese counterparts. Similar percentages of women with and without obesity reported consuming medications in the remaining medication classes including central nervous system agents (50 and 46%), gastrointestinal drugs (43 and 40%), anti-infective agents (23 and 21%), antihistamines (20 and 17%), autonomic drugs (10 and 9%), and respiratory tract agents (7 and 6%), respectively (p > 0.05 for all adjusted comparisons). There were no differences in medication use by obesity status across gestation. Since the study exclusion criteria limited the non-obese group to women without thyroid disease, in a sensitivity analysis we excluded all women who reported thyroid medication intake and still a higher proportion of women with obesity took the hormones and synthetic substitutes class compared to women without obesity. [ABSTRACT FROM AUTHOR]