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Objective Design Setting Population Methods Main outcome measures Results Conclusions To evaluate the associations of plasma polybrominated diphenyl ether (PBDE) concentrations in early pregnancy with gestational weight gain (GWG).Prospective cohort study.US‐based, multicentre cohort of pregnant women.We used data from 2052 women without obesity and 397 women with obesity participating in the NICHD Fetal Growth Studies – Singleton Cohort, with first‐trimester plasma PBDE concentrations and weight measurements throughout pregnancy.We applied generalised linear models and Bayesian kernel machine regression (BKMR) to evaluate both the individual and joint associations of PBDEs with measures of GWG, adjusting for potential confounders.Total GWG (kg), total and trimester‐specific GWG velocities (kg/week), and GWG categories and trajectory groups.Mean pre‐pregnancy BMIs were 23.6 and 34.5 kg/m2 for women without and with obesity, respectively. Among women without obesity, there were no associations of PBDEs with any GWG measure. Among women with obesity, one standard deviation increase in log‐transformed PBDE 47 was associated with a 1.87 kg higher total GWG (95% CI 0.39–3.35) and a 0.05 kg/week higher total GWG velocity (95% CI 0.01–0.09). Similar associations were found for PBDE 47 in BKMR among women with obesity, and PBDE 47, 99 and 100 were associated with lower odds of being in the low GWG trajectory group.PBDEs were not associated with GWG among individuals without obesity. Among those with obesity, only PBDE 47 showed consistent positive associations with GWG measures across multiple statistical methods. Further research is needed to validate this association and explore potential mechanisms. [ABSTRACT FROM AUTHOR]

Is self-reported psychological stress associated with markers of ovarian reserve among subfertile women? Observational study of women (n = 520) seeking fertility care at the Massachusetts General Hospital who enrolled in the Environment and Reproductive Health study between 2005 and 2019. Women completed the short version of the validated PSS4, which assesses psychological stress. Ovarian reserve markers included AFC and circulating serum levels of day-3 FSH, with AMH assessed in a subset of participants (n = 185). Higher total PSS4 scores were negatively associated with AFC and serum AMH levels. Analyses adjusted for age, BMI, race, smoking, education, physical activity and type of infertility diagnosis. Women in the second and third tertiles of stress had lower AFC (13.3, 95% CI 12.7 to 13.8; and 13.5, 95% CI 13.0 to 14.1) compared with women in the lowest tertile of psychological stress score (14.3, 95% CI 13.8 to 14.9, both P < 0.05). Women in the second and third tertiles of total PSS4 scores also had lower mean serum AMH compared with women in the lowest tertile (2.99, 95% CI 2.24 to 3.74), and (2.99 95% CI 2.22 to 3.76) versus (3.94 95% CI 3.23 to 4.64). These associations varied by several socioeconomic factors, and were observed among women who were younger, belonging to minority races, with a college degree or with annual household income less than $100,000. Higher perceived stress was negatively associated with AFC and serum AMH levels. These associations varied by several socioeconomic factors. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Are occupational factors associated with markers of testicular function among men attending a fertility center? SUMMARY ANSWER Men working non-daytime/rotating shifts and those with physically demanding jobs have higher sperm concentration and total sperm count as well as higher estradiol and total testosterone concentrations. WHAT IS KNOWN ALREADY Semen quality has declined during recent decades and has been negatively correlated with higher risks of common chronic diseases and mortality, highlighting its public health importance beyond fertility and reproduction. While most of the previous epidemiology literature on male fertility has focused on environmental exposures, dietary factors, and other related variables, little attention has been paid to occupational factors. STUDY DESIGN, SIZE, DURATION This observational study included 377 men who were male partners in couples seeking infertility treatment at a fertility center, who enrolled in the Environment and Reproductive Health (EARTH) study between 2005 and 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS Self-reported information on lifting/moving heavy objects, typical shift, and physical level of exertion at work was collected from a take-home questionnaire. Semen samples were analyzed following World Health Organization guidelines. Enzyme immunoassays were used to assess reproductive hormone concentrations. Linear regression models were used to evaluate the association between occupational factors and measures of testicular function, while adjusting for covariates such as age, BMI, education, race, smoking, and abstinence time, and accounting for multiple semen samples (mean = 2, min–max = 1–9) in analyses for semen parameters. MAIN RESULTS AND THE ROLE OF CHANCE Men had a median (interquartile range) age of 36 (33, 39) years and were predominantly Caucasian (87%). Of the men who completed the survey, 12% reported often lifting or moving heavy objects at work, 6% reported heavy physical exertion at work, and 9% reported evening or rotating shifts. Men who reported often lifting or moving heavy objects at work had 46% higher sperm concentrations (P  = 0.01) and 44% higher total counts (P  = 0.01) compared with men who reported never lifting or moving heavy objects at work. Similar results were found for men working in rotating shifts compared to those in day shifts, as well as for men involved in heavy levels of physical exertion compared to those with light levels at work. We also found that men involved in heavy/moderate levels of physical exertion at work had higher circulating testosterone concentrations compared to those with lighter exertion (adjusted means of 515 and 427 ng/dl, respectively, P  = 0.08), and men who often moved/lifted heavy objects at work had higher estradiol concentrations, compared to those who never did (adjusted means of 36.8 and 27.1 pg/ml, respectively, P  = 0.07). Men working evening/rotating shifts had 24% higher testosterone (P  = 0.04) and 45% higher estradiol concentrations (P  = 0.01), compared to men working day shifts. No associations were observed for ejaculated volume, total motility, morphologically normal sperm, or serum FSH and LH concentrations. LIMITATIONS, REASONS FOR CAUTION Due to our study design which recruited men from couples seeking fertility treatment, it may not be possible to generalize our findings to men from the general population. Also, as is the case of all studies based on self-reported questionnaires, measurement error and misclassification of the exposure are potential concerns. WIDER IMPLICATIONS OF THE FINDINGS Physically demanding jobs and rotating or evening shift occupations may be associated with higher testicular function in men measured as higher sperm concentrations and counts as well as higher serum testosterone and estradiol levels. Confirmation of these findings in other non-fertility clinic study populations is warranted. STUDY FUNDING/COMPETING INTEREST(S) NIH grants R01ES022955, R01ES009718, R01ES033651, and R01ES000002 from the National Institute of Environmental Health Sciences (NIEHS) and Legacy, Inc. R.A.G. works part time for Legacy, Inc. which provided funds to perform this analysis. There are no other conflicts of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Background: Combination antiretroviral therapy (cART) initiation during pregnancy reduces the risk of perinatal human immunodeficiency virus (HIV) transmission; however, studies have suggested that there may be unintended adverse consequences on birth outcomes for selected cART regimens.Methods: We analyzed adverse birth outcomes among a prospective cohort of 1307 pregnant women with HIV in Dar es Salaam who initiated cART during the first or second trimester of a singleton pregnancy. Our primary analysis compared birth outcomes by gestational age at cART initiation among these women initiating cART in pregnancy.Results: Among women who initiated cART in pregnancy, there was no relationship of gestational age at cART initiation with the risk of fetal death or stillbirth. However, women who initiated cART before 20 weeks of gestation compared with after 20 weeks had increased risk of preterm birth (risk ratio [RR], 1.30; 95% confidence interval [CI], 1.03-1.67) but decreased risk of small-for-gestational age birth (RR, 0.71; 95% CI, .55-.93).Conclusions: With increasing use of cART preconception and early in pregnancy, clinicians should be aware of the benefits and potential risks of cART regimens to optimize birth outcomes. [ABSTRACT FROM AUTHOR]

[Display omitted] The menopausal transition involves significant sex hormone changes. Environmental chemicals, such as urinary phthalate metabolites, are associated with sex hormone levels in cross-sectional studies. Few studies have assessed longitudinal associations between urinary phthalate metabolite concentrations and sex hormone levels during menopausal transition. Pre- and perimenopausal women from the Midlife Women's Health Study (MWHS) (n = 751) contributed data at up to 4 annual study visits. We quantified 9 individual urinary phthalate metabolites and 5 summary measures (e.g., phthalates in plastics (∑Plastic)), using pooled annual urine samples. We measured serum estradiol, testosterone, and progesterone collected at each study visit, unrelated to menstrual cycling. Linear mixed-effects models and hierarchical Bayesian kernel machine regression analyses evaluated adjusted associations between individual and phthalate mixtures with sex steroid hormones longitudinally. We observed associations between increased concentrations of certain phthalate metabolites and lower testosterone and higher sub-ovulatory progesterone levels, e.g., doubling of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), di-2-ethylhexyl phthalate (∑DEHP) metabolites, ∑Plastic, and ∑Phthalates concentrations were associated with lower testosterone (e.g., for ∑DEHP: −4.51%; 95% CI: −6.72%, −2.26%). For each doubling of MEP, certain DEHP metabolites, and summary measures, we observed higher mean sub-ovulatory progesterone (e.g., ∑AA (metabolites with anti-androgenic activity): 6.88%; 95% CI: 1.94%, 12.1%). Higher levels of the overall time-varying phthalate mixture were associated with lower estradiol and higher progesterone levels, especially for 2nd year exposures. Phthalates were longitudinally associated with sex hormone levels during the menopausal transition. Future research should assess such associations and potential health impacts during this understudied period. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: Youth with perinatal HIV exposure have demonstrated high rates of emotional–behavioral problems. Few studies have longitudinally examined racial/ethnic disparities in such functioning across adolescence, a critical time for targeting prevention/intervention efforts. Setting: The Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol is one of the largest US-based cohort studies of youth with perinatal HIV (YPHIV) infection or HIV exposed but uninfected (YPHEU). Methods: Youth and caregivers individually completed the Behavior Assessment System for Children, second edition, every 2 years between ages 7 and 19 years. We used adjusted mixed-effects models to evaluate whether mean youth-reported emotional concerns and caregiver-reported behavioral concerns differed by race/ethnicity. We used group-based trajectory models to identify groups having similar emotional–behavioral trajectories, followed by multinomial models to determine which factors predicted group membership. Results: Three hundred ninety-one YPHIV and 209 YPHEU (7% White non-Hispanic, 21% White Hispanic, 66% Black non-Hispanic, and 6% Black Hispanic) completed a median of 4 assessments over follow-up. Adjusted models showed more caregiver-reported behavioral concerns for Black non-Hispanic YPHEU than for Black non-Hispanic YPHIV, White Hispanic YPHIV, and White Hispanic YPHEU, particularly later in adolescence. Race/ethnicity did not predict membership in subgroups of youth-reported emotional or caregiver-reported behavioral functioning identified using group-based trajectory models. However, factors predicting membership in vulnerable youth-reported emotional and caregiver-reported behavioral groups included experiencing a stressful life event and living with a caregiver who was married or screened positive for a psychiatric condition. Conclusions: Our study revealed that Black non-Hispanic YPHEU are a vulnerable subgroup. Contributing factors that could inform interventions include the caregiver's health, household characteristics, and psychiatric status. [ABSTRACT FROM AUTHOR]

Study Question: Are peripubertal blood lead levels (BLLs) associated with semen parameters and serum reproductive hormones among young Russian men?Summary Answer: We observed a suggestion of lower ejaculate volume with higher peripubertal BLL but no associations of BLLs with reproductive hormones measured throughout adolescence or with other sperm parameters measured at adulthood.What Is Known Already: Lead is a known reproductive toxicant and endocrine disruptor. Previous literature has shown associations between high lead exposure and poorer semen quality both in occupationally and environmentally exposed men. However, to our knowledge, no longitudinal studies have explored the association of childhood lead exposure with semen parameters and reproductive hormones in young men.Study Design, Size, Duration: The Russian Children's Study is a prospective cohort study that enrolled 516 boys at age 8-9 years in 2003-2005 and followed them annually for 10 years. BLLs were measured at entry and lifestyle and health questionnaires were completed. Reproductive hormones were measured in blood samples collected every 2 years.Participants/materials, Setting, Methods: Among the 516 boys enrolled, 481 had BLLs measured at entry. Of these, 453 had at least one measurement of serum testosterone, follicle stimulating hormone (FSH) or luteinizing hormone (LH) (median = 5 samples per boy) and 223 had semen samples collected ∼10 years after enrolment. Semen assessment included ejaculated volume, sperm concentration, progressive motility and total sperm count, and parameters were categorized using published andrology standards for low semen quality based on sperm count and motility. Linear mixed models were used to examine the associations of log-transformed BLLs (and BLL categories) with reproductive hormones and semen parameters, adjusting for potential confounders.Main Results and the Role Of Chance: Among the 223 young men with peripubertal BLLs and at least one semen sample (total samples = 438), the median (interquartile range) BLL was 3 (2, 5) µg/dl and 27% had BLL ≥5 µg/dl. Overall, 49% of the semen samples fell below reference levels for sperm count and/or motility. Men with peripubertal BLL ≥5 µg/dl had significantly lower ejaculated volume than those with BLL <5 µg/dl (mean = 2.42 vs 2.89 ml, P = 0.02), but this difference was attenuated in adjusted models (mean = 2.60 vs 2.83 ml, P = 0.25). No associations were observed between BLL measured at age 8-9 years and reproductive hormone levels or sperm parameters, including sperm concentration, total count, progressive motility and total progressive motile sperm count, or with the probability of having low semen quality based on sperm count/motility.Limitations, Reasons For Caution: Only a subset of the original cohort participated in the semen quality portion of the study, although inverse probability weighting was used to account for possible selection bias. BLLs were only measured at a single time in peripuberty, and other exposure time periods, including later or longer-term childhood exposure, may be more predictive of semen quality. The young men were also exposed to other chemical contaminants before and during pubertal development.Wider Implications Of the Findings: While semen volume often receives less attention than other sperm parameters, it is an important component of male fertility. Additional prospective studies covering different exposure windows and including other seminal plasma biomarkers are warranted to explore our finding of potentially lower ejaculated volume with higher BLLs and to confirm the lack of associations for other semen parameters among youth exposed to environmental BLLs.Study Funding/competing Interest(s): Funding was provided through grants R01ES0014370 and P30ES000002 from the National Institute of Environmental Health Sciences, grant R82943701 from the U.S. Environmental Protection Agency, and grant 18-15-00202 from the Russian Science Foundation (O.S and Y.D.). All authors report no competing interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: Youth with perinatal HIV exposure have demonstrated high rates of emotional-behavioral problems. Few studies have longitudinally examined racial/ethnic disparities in such functioning across adolescence, a critical time for targeting prevention/intervention efforts. Setting: The Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol is one of the largest US-based cohort studies of youth with perinatal HIV (YPHIV) infection or HIV exposed but uninfected (YPHEU). Methods: Youth and caregivers individually completed the Behavior Assessment System for Children, second edition, every 2 years between ages 7 and 19 years. We used adjusted mixed-effects models to evaluate whether mean youth-reported emotional concerns and caregiverreported behavioral concerns differed by race/ethnicity. We used group-based trajectory models to identify groups having similar emotional-behavioral trajectories, followed by multinomial models to determine which factors predicted group membership. Results: Three hundred ninety-one YPHIV and 209 YPHEU (7% White non-Hispanic, 21% White Hispanic, 66% Black non-Hispanic, and 6% Black Hispanic) completed a median of 4 assessments over follow-up. Adjusted models showed more caregiver-reported behavioral concerns for Black non-Hispanic YPHEU than for Black non-Hispanic YPHIV, White Hispanic YPHIV, and White Hispanic YPHEU, particularly later in adolescence. Race/ethnicity did not predict membership in subgroups of youth-reported emotional or caregiver-reported behavioral functioning identified using group-based trajectory models. However, factors predicting membership in vulnerable youth-reported emotional and caregiver-reported behavioral groups included experiencing a stressful life event and living with a caregiver who was married or screened positive for a psychiatric condition. Conclusions: Our study revealed that Black non-Hispanic YPHEU are a vulnerable subgroup. Contributing factors that could inform interventions include the caregiver's health, household characteristics, and psychiatric status. [ABSTRACT FROM AUTHOR]

Background: Few studies have evaluated physical activity patterns or their association with vascular inflammation among youth living with perinatally acquired HIV (YPHIV). Methods: We assessed YPHIV and youth perinatally HIV-exposed but uninfected (YPHEU) in the PHACS Adolescent Master Protocol with at least one Block physical activity questionnaire (PAQ) completed between ages 7-19 years. Physical activity metrics were as follows: (1) daily total energy expenditure (TEE) and (2) physical activity duration (PAD) defined as the minutes of daily moderate and vigorous activities. In a subgroup, we measured serum biomarkers of coagulation (fibrinogen and P-selectin) and endothelial dysfunction (soluble intracellular cell adhesion molecule-1, soluble vascular cell adhesion molecule-1, and E-selectin) obtained within 3 months of a single PAQ. Repeated measures linear regression models were used to compare the trajectories of log-transformed TEE and PAD by HIV status, adjusting for confounders. Spearman correlations were calculated to assess the relationship of TEE and PAD with vascular biomarkers. Results: Five hundred ninety-six youth (387 YPHIV and 209 YPHEU) completed 1552 PAQs (median PAQs completed = 3). The median age at enrollment (Q1, Q3) was 11 (9, 13) years. TEE and PAD increased with age in both YPHIV and YPHEU. However, even after adjusting for confounders, YPHIV had significantly less increase per year than YPHEU for TEE (5.7% [95% confidence interval (CI): -9.9% to -1.4%, P = 0.010] less) and PAD (5.2% [95% CI: -9.2% to -1.1%, P = 0.016] less). Among 302 youth with biomarker measures (187 YPHIV and 114 YPHEU), we observed little correlation with TEE or PAD. Conclusions: Both groups had increases in physical activity levels as they aged, but YPHIV had smaller increases throughout adolescence compared with YPHEU, which may impact longterm health. [ABSTRACT FROM AUTHOR]

Background: Childhood exposure to organochlorines has been associated with alterations in somatic growth. We evaluated the associations of peri-pubertal serum levels of dioxin-like compounds (DLCs) and nondioxin-like polychlorinated biphenyls (NDL-PCBs), with adolescent growth, body composition, and near adult height (NAH) in a longitudinal cohort study of Russian boys.Methods: 473 8-9 year-old boys had serum DLCs and associated toxic equivalents (TEQs) and NDL-PCBs concentrations measured. Physical examinations were performed at enrollment between 2003 and 2005, and annually over 11 years to 2016; annual bio-electric impedance analysis (BIA) of body composition began in 2006. We used mixed effects models to evaluate associations of quartiles of serum chemical concentrations with longitudinal measurements through age 19 of body mass index (BMI-Z) and height (HT-Z) z-scores, annual height velocity (HV), and BIA-derived height-adjusted fat (FMi) and fat-free mass (FFMi) indexes. Potential modification by age of the associations of chemical exposures with growth was evaluated. NAH (defined as HV < 1 cm/year) and age at NAH attainment were estimated using parametric survival models accounting for right censoring.Results: The medians of serum ∑TEQs, ∑DLCs, and ∑NDL-PCBs were 21.1 pg TEQ/g lipid, 362 pg/g lipid, and 250 ng/g lipid, respectively. In multivariable models, higher serum concentrations of peri-pubertal ∑TEQs, ∑DLCs, and ∑NDL-PCBs were associated with significantly lower BMI-Z, FMi, and FFMi over 11 years of follow-up. The differences in FFMi for boys with higher versus lower ΣTEQs and ΣNDL-PCBs increased with age. In multivariable models, higher ∑NDL-PCBs were associated with lower HT-Z, with attenuation of the association with age (interaction p < 0.001). The highest versus the lowest quartiles of ∑NDL-PCBs were not associated with differences in NAH, but were associated with an average of 6 months later attainment of NAH.Conclusions: Our findings suggest that dioxin and NDL-PCB exposures during childhood are associated with alterations in body composition and subsequent somatic growth. [ABSTRACT FROM AUTHOR]

Peripubertal concentrations of serum dioxins and polychlorinated biphenyls (PCBs) have demonstrated associations with altered age of pubertal onset and sexual maturity in boys, but associations with pubertal progression have received less attention. The Russian Children's Study is a prospective cohort of 516 boys enrolled in 2003–2005 at age 8 or 9 and followed annually up to 19 years of age. Serum concentrations of dioxin-like toxic equivalents (TEQs), polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and non-dioxin-like PCBs (NDL-PCBs) and whole blood lead levels (BLLs) were quantified from blood samples collected at study entry (age 8–9). Testicular volume (TV) was assessed annually using a Prader orchidometer. Pubertal trajectories were identified by applying Group-Based Trajectory Models (GBTMs) to TV measured from ages 8–19. Associations of peripubertal serum TEQs, PCDDs, PCDFs, and NDL-PCBs with specific progression trajectories were modeled using multinomial logistic regression, adjusting for each boy's birthweight, and for BLL, body mass index and nutritional factors at study entry. Among 489 eligible boys with available exposure measures, we identified three pubertal trajectories using GBTMs: slower (34% of boys), moderate (48%) and faster (18%). Boys with higher peripubertal serum TEQs had higher adjusted odds of being in the moderate versus faster trajectory (adjusted odds ratio (aOR) 1.79, 95% CI 1.01, 3.13) and the slower versus faster trajectory (aOR 1.52, 95% CI 0.82, 2.78) per 1 log unit increase in serum TEQs. Boys with higher peripubertal serum PCDFs had higher adjusted odds of being in the moderate compared to the faster trajectory (aOR 1.92, 95% CI 1.20, 3.03) and of being in the slower versus the faster trajectory (aOR 1.42, 95% CI 0.91, 2.33) per 1 log unit increase. Boys with higher NDL-PCBs had higher adjusted odds of being in the faster trajectory versus the moderate (aOR 2.56, 95% CI 0.91–7.20) or slower (aOR 3.31, 95% CI 1.07, 10.25) trajectory. Boys with higher blood lead levels also had higher adjusted odds of being in the slower trajectory of pubertal progression, compared to either the faster (aOR 1.47, 95% CI 0.89, 2.44) or moderate (aOR 1.20, 95% CI 0.83, 1.75) trajectories, per 1 log unit increase in BLL, although these associations did not attain statistical significance. Boys' peripubertal exposure to dioxins and certain PCBs may alter pubertal progression. • Few studies have examined links of environmental exposures with pubertal progression. • We studied associations of dioxins & PCBs with pubertal progression in Russian boys. • We identified subgroups of boys with slow, moderate or faster pubertal trajectories. • Boys with higher dioxin TEQs more often had slower-paced pubertal trajectories. • Boys with higher non-dioxin-like PCB levels more often had faster trajectories. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: Disordered bone mineral metabolism and low vitamin D concentrations are associated with cardiovascular abnormalities; few studies have evaluated this relationship in HIV-infected youth. Setting: The Adolescent Master Protocol is a Pediatric HIV/AIDS Cohort Study network study conducted across 14 US sites. Methods: Among perinatally HIV-infected (PHIV) and perinatally HIV-exposed but uninfected (PHEU) youth enrolled in the Adolescent Master Protocol, we evaluated associations of vitamin D [measured as 25-hydroxy-vitamin D (25-OHD)], parathyroid hormone (PTH), calcium, phosphate, and fibroblast growth factor-23 (FGF-23) concentrations with echocardiographic measures of left ventricular (LV) structure, function, and concentrations of NT-proBNP, a biomarker of cardiac damage. Results: Among 485 participants (305 PHIV and 180 PHEU) with echocardiograms and bone mineralization measures, low 25-OHD (<20 ng/mL) was common among all participants (48% PHIV and 44% PHEU), but elevated PTH (>65 pg/mL) was identified more often among PHIV participants than PHEU participants (9% vs 3%, P = 0.02). After adjusting for HIV status and demographic covariates, both low 25-OHD and elevated PTH were associated with lower mean LV mass z-scores, whereas elevated PTH was associated with higher mean fractional shortening z-scores. Participants with low 25-OHD also had slightly higher mean LV end-systolic wall stress z-scores, but differences were more pronounced in PHEU participants than in PHIV participants. FGF-23 was inversely related to end-diastolic septal thickness, both overall and among PHIV participants. Conclusions: In this cohort of PHIV and PHEU youth, we observed associations of 25-OHD, PTH, and FGF-23 with both structural and functional cardiac parameters, supporting links between bone mineral metabolism and cardiac status. [ABSTRACT FROM AUTHOR]

Abstract Background Higher blood lead levels (BLLs) have been linked to neurologic deficits and impaired growth, but few studies have evaluated their association with timing of sexual maturity or pubertal progression in boys. Methods In a longitudinal cohort of Russian boys enrolled at age 8–9 and followed to adulthood, BLLs were measured at study entry, and pubertal staging (genitalia and pubic hair) and testicular volume (TV) measurements were obtained annually. We used interval-censored regression models to estimate differences between boys with higher BLL (≥5 μg/dL) and lower BLL in mean ages at sexual maturity (genitalia stage 5, pubic hair stage 5, or TV ≥ 20 mL) and duration of pubertal progression (onset to maturity), adjusting for potential confounders. Mediation analyses were conducted to quantify the percent of lead's effect attributable to its association with reduced somatic growth. Results Among 481 evaluable boys, 28% had BLL ≥ 5 μg/dL. Adjusted mean ages at sexual maturity were 14.7 years for genitalia, 16.1 for pubic hair, and 13.9 for TV. In adjusted models, boys with BLLs ≥5 μg/dL had later maturity than those with lower levels by 4–5 months depending on pubertal indicator. In mediation analyses, height and body mass index at age 11 accounted for 40–71% of the shift in age at maturity for boys with higher compared to lower BLLs. Higher BLLs were not associated with pace of pubertal progression. Conclusions Higher lead levels were associated with later attainment of sexual maturity in males, but not with the duration of pubertal progression. A high proportion of the delay in sexual maturity for boys with higher as compared to lower BLL was shown to be attributable to mediating effects of BLL on reduced growth. Highlights • Higher blood lead has been linked to impaired growth and delayed pubertal onset. • Few studies have addressed the effects of blood lead on age at male sexual maturity. • We found significant delays in maturity among Russian boys with higher lead levels. • This delay was partly due to reduced growth among boys with higher lead levels. • Higher blood lead did not appear to slow pubertal progression. [ABSTRACT FROM AUTHOR]

Abstract Background Exposure to some environmental chemicals is ubiquitous and linked to a variety of adverse outcomes, including children's health. While few studies have assessed the contribution of both male and female exposures to children's health, understanding the patterns of couple's exposure is needed to understand their joint effects. Objective We assessed the correlation patterns between male and female partners' concentrations of 37 environmental chemical biomarkers. We also assessed the temporal reliability of the biomarkers within couples. Methods We calculated Spearman pairwise correlations between specific gravity adjusted urinary biomarker concentrations and hair mercury concentrations among 380 couples enrolled in the Environment and Reproductive Health (EARTH) study at the Massachusetts General Hospital Fertility Center (2004–2017). We calculated intra-class correlation coefficients (ICCs) for couple's biomarkers to assess the temporal variability of these exposures within a couple using multiple paired-samples from couples. Results All biomarkers were positively correlated within couples (range: 0.05 for tert -butylphenyl phenyl phosphate to 0.66 for triclosan). In general, the biomarkers with the highest within couple correlation were those of chemicals for which diet (e.g., di(2-ethylhexyl) phthalate), personal care products use (e.g., triclosan, benzophenone-3), and the indoor environment (e.g., 2,5-dichlorophenol) are considered primary exposure sources. Most other biomarkers were moderately correlated (0.3–<0.6). Similar patterns of temporal reliability were observed across biomarkers. Conclusions Urinary concentrations of several biomarkers were mostly moderately correlated within couples, suggesting similar exposure sources. Future epidemiological studies should collect samples from both partners to be able to accurately determine the contribution of maternal and paternal exposures to offspring health. Highlights • Understanding the patterns of couple's exposure is needed to understand their joint effects. • All 37 environmental biomarkers were positively correlated within couples. • Correlations were moderately high for chemicals with diet, personal products, and indoor environment are primary sources. • Similar patterns were observed across biomarkers for measures of temporal reliability. [ABSTRACT FROM AUTHOR]

Combination antiretroviral regimens have achieved tremendous success in reducing perinatal HIV transmission, and have become standard of care in pregnant women with HIV. However, the large variety of combination antiretroviral regimens utilized in practice raises the question of whether some of these highly potent drugs pose other risks to the pregnancy or infant. While HIV-infected pregnant women are almost always exposed to multiple antiretrovirals concurrently, standard safety screening strategies typically consider each individual antiretroviral separately, which fails to account for potential confounding due to simultaneous exposure to other antiretrovirals. In this paper, we evaluate a hierarchical modeling approach which groups antiretrovirals by drug class to screen for the safety of antiretrovirals taken during pregnancy, while still providing individual antiretroviral drug effect estimates. In simulation studies, we observed that the hierarchical approach may be advantageous as compared to considering each antiretroviral drug separately or simultaneously evaluating all antiretrovirals in a fixed effect model, particularly when there is prior evidence suggesting drugs from the same class behave similarly on the outcome. The characteristics of the hierarchical approach are illustrated in an application evaluating risk of preterm birth using a study including over 2000 pregnancies representing over 100 antiretroviral combinations, each involving up to three drug classes. [ABSTRACT FROM AUTHOR]

Abstract Background Multiple meta-analyses have shown sperm count declines in Western countries spanning eight decades. Secular trends in other parameters remain unclear, as are potential predictors of these trends. Objective To analyze secular trends in semen quality and to evaluate whether factors previously found to be related to semen quality were responsible for these patterns. Methods This is a prospective study including 936 men of couples seeking infertility treatment who provided 1618 semen samples at a single center (2000–2017). Self-reported demographic, nutritional and reproductive characteristics were collected using standardized questionnaires. Urinary concentrations of bisphenol A, parabens and phthalates were quantified by isotope-dilution tandem mass spectrometry. Semen samples were analyzed for volume, sperm concentration, count, motility and morphology following WHO guidelines. We estimated the differences in semen parameters over time by fitting generalized linear mixed models with random intercepts to account for repeated samples while adjusting for abstinence time. We also adjusted for demographic, nutritional and environmental factors to investigate these as potential predictors of time trends. Results Sperm concentration and count declined by 2.62% per year (95% CI −3.84, −1.38) and 3.12% per year (95% CI: −4.42, −1.80), corresponding to an overall decline of 37% and 42%, respectively, between 2000 and 2017. Decreasing trends were also observed for total motility (per year: −0.44 percentage units, 95% CI −0.71, −0.17) and morphologically normal sperm (per year: −0.069 percentage units, 95% CI −0.116, −0.023). These decreases reflected relative percentage declines of 15% and 16% over the 17 year study period, respectively. When reproductive factors were included in the model, the downward trends in sperm concentration and sperm count were attenuated by 29% and 26%, respectively, while the trends in motility and morphology were attenuated by 54% and 53%, respectively. Also, the downward trends in both sperm concentration and sperm morphology over time were attenuated by 19% when including the DEHP and non-DEHP metabolites, respectively. Conclusions Sperm concentration, total count, motility and morphology significantly declined between 2000 and 2017 among subfertile men. These negative trends were attenuated when considering simultaneous changes in reproductive characteristics and urinary phthalates during the course of the study. Highlights • Sperm concentration and count declined 37% and 42%, respectively, between 2000 and 2017 among men attending a fertility center in Boston. • Total motility and morphologically normal sperm declined 15% and 16% over the 17 year study period, respectively. • When reproductive factors were included in the model, the downward trends in semen parameters were attenuated between 29% and 54%. • The downward trends in sperm concentration and morphology were attenuated by 19% when including the DEHP and non-DEHP metabolites, respectively. [ABSTRACT FROM AUTHOR]

The risk difference scale is often of primary interest when evaluating public health impacts of interventions on binary outcomes. However, few investigators report findings in terms of additive interaction, probably because the models typically used for binary outcomes implicitly measure interaction on the multiplicative scale. One measure with which to assess additive interaction from multiplicative models is the relative excess risk due to interaction (RERI). The RERI measure has been applied in many contexts, but one limitation of previous approaches is that clustering in data has rarely been considered. We evaluated the RERI metric for the setting of clustered data using both population-averaged and cluster-conditional models. In simulation studies, we found that estimation and inference for the RERI using population-averaged models was straightforward. However, frequentist implementations of cluster-conditional models including random intercepts often failed to converge or produced degenerate variance estimates. We developed a Bayesian implementation of log binomial random-intercept models, which represents an attractive alternative for estimating the RERI in cluster-conditional models. We applied the methods to an observational study of adverse birth outcomes in mothers with human immunodeficiency virus, in which mothers were clustered within clinical research sites. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: In utero exposure to nucleoside reverse transcriptase inhibitor (NRTI)-containing antiretroviral treatment (ART) regimens may be associated with poor neurodevelopmental functioning in children of HIV-infected mothers. We investigated neurodevelopmental outcomes of HIV-exposed uninfected (HEU) children of HIV-infected women enrolled in a randomized trial of abacavir/zidovudine/lamivudine (triple-NRTI regimen) vs. lopinavir/ritonavir/zidovudine/lamivudine [dual-NRTI + protease inhibitor (PI) regimen]. Setting: The Mma Bana randomized trial was conducted in urban and rural sites in Botswana. Methods: The Mma Bana study randomized HIV-infected pregnant women with CD4 ≥200 cells per mm3 to a triple-NRTI vs. dual-NRTI + PI regimen from 26- to 34-week gestation through planned weaning at 6-month postpartum. Partway through the study, neurodevelopmental assessments were added at 24 months of age, including the Developmental Milestones Checklist, the Bayley Scales of Infant and Toddler Development third edition, Ten Questions Questionnaire, and Profile of Social Emotional Development. We evaluated differences in mean scores between the 2 arms using unadjusted and adjusted linear regression. Results: A total of 197 HEU infants (48% male) completed a neurodevelopmental assessment (101 in triple-NRTI arm and 96 in dual-NRTI + PI-exposed arm). Mean values for all neurodevelopmental outcomes were similar for children of mothers randomized to either ART regimen, with no significant differences in either unadjusted or adjusted models (estimated effect sizes ranging from −0.12 to 0.14). Conclusions: Neurodevelopmental outcomes in 24-month-old HEU children of HIV-infected mothers with baseline CD4 ≥200 were similar in those randomized to a dual-NRTI + PI–based vs. a triple-NRTI–based ART regimen, suggestive of lack of short-term toxicity. Monitoring of long-term toxicity and newer regimens is warranted. [ABSTRACT FROM AUTHOR]

Abstract Objectives To examine the associations of maternal intake of fruits and vegetables (FVs), considering pesticide residue levels, with fetal growth. Methods We studied 1777 mothers (1275 white, 502 non-white) and their infants from Project Viva, a prospective pre-birth cohort (1999–2002). We categorized FVs as containing high or low pesticide residues using data from the US Department of Agriculture. We then used a food frequency questionnaire to estimate each participant's intake of high and low pesticide residue FVs in the first and second trimester. The primary outcomes were small-for-gestational-age (SGA; <10th percentile in birth-weight-for-gestational-age), large-for-gestational-age (LGA; ≥10th percentile in birth-weight-for-gestational-age) and preterm birth (gestational age <37 weeks). We also evaluated whether the associations between high pesticide residue FV intake and birth outcomes were modified by race/ethnicity. Results 5.5% of newborns were SGA, 13.7% were LGA, and 7.3% were preterm. Intakes of high or low pesticide residue FVs, regardless of pregnancy trimester, were not associated with risks of SGA, LGA, or preterm birth. In addition, the associations of high pesticide FV intake with SGA and LGA were not modified by race/ethnicity. However, we observed heterogeneity in the relationship between first trimester high pesticide FV intake and risk of preterm birth by race/ethnicity (P value for interaction = 0.01), although this relationship did not persist after correction for multiple comparisons (Bonferroni corrected level of significance: P < 2.8 × 10−3). Conclusions There were no clear associations between high or low pesticide FV intake during pregnancy with SGA, LGA or preterm birth. Highlights • Little is known about whether intake of pesticide residues from FVs during pregnancy may have adverse effects on offspring. • Neither intake of high or low pesticide residue FVs during pregnancy was associated with preterm birth or fetal growth. • More studies are needed to investigate the impact of prenatal pesticide exposure on birth and later childhood outcomes. [ABSTRACT FROM AUTHOR]

Study Question: Are maternal and paternal preconception urinary bisphenol A (BPA) or bisphenol S (BPS) concentrations associated with offspring birth size?Summary Answer: Maternal-but not paternal-preconception urinary BPA concentrations were associated with lower birth size among couples seeking fertility evaluation.What Is Known Already: Prenatal BPA exposure has been previously associated with reduced birth size in some but not all epidemiologic studies. However, the potential effect of BPA exposure before conception in either parent is unknown. Data on BPS is practically absent.Study Design, Size, Duration: Ongoing prospective preconception cohort of women and men seeking fertility evaluation between 2005 and 2016 in a large fertility center in an academic hospital in Boston, MA, USA.Participants/materials, Setting, Methods: We examined the association between maternal and paternal preconception, as well as maternal prenatal urinary BPA and BPS concentrations, and size at birth among 346 singletons from couples recruited in the Environment and Reproductive Health (EARTH) Study using multivariable linear regression. Infant birth weight and head circumference were abstracted from delivery records. Mean preconception and prenatal exposures were estimated by averaging urinary ln-BPA and ln-BPS concentrations in multiple maternal and paternal urine samples collected before pregnancy, and maternal pregnancy samples collected in each trimester.Main Results and the Role Of Chance: Maternal preconception urinary BPA concentrations were inversely associated with birth weight and head circumference in adjusted models: each ln-unit increase was associated with a decrease in birth weight of 119 g (95% CI: -212, -27), and a head circumference decrease of 0.72 cm (95% CI: -1.3, -0.1). Additional adjustment by gestational age or prenatal BPA exposure modestly attenuated results. Women with higher prenatal BPA concentrations had infants with lower mean birth weight (-75 g, 95% CI: -153, 2) although this did not achieve statistical significance. Paternal preconception urinary BPA concentrations were not associated with either birth weight or head circumference. No consistent patterns emerged for BPS concentrations measured in either parent.Limitations, Reasons For Caution: We observed a strong negative association between maternal-but not paternal-preconception BPA concentrations and offspring birth size among a subfertile population. Although these results are overall consistent with prior studies on prenatal BPA exposure, these findings may not be generalizable to women without fertility concerns.Wider Implications Of the Findings: This study suggests that the unexplored maternal preconception period may be a sensitive window for BPA effects on birth outcomes.Study Funding/competing Interest(s): Work supported by Grants (ES R01 009718, ES 022955 and ES 000002) from the National Institute of Environmental Health Sciences (NIEHS). C.M. was supported by a post-doctoral fellowship award from the Canadian Institutes of Health Research. There are no competing interests to declare. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Epidemiologic studies of the effects of parental preconception paraben exposures on child behavior are limited despite emerging evidence suggesting that such exposures may affect offspring neurodevelopment.We investigated whether maternal and paternal preconception and maternal pregnancy urinary concentrations of parabens were associated with child behavior.We analyzed data from the Preconception Environmental exposure And Childhood health Effects Study, an ongoing prospective cohort of children aged 6–13 years and their parents. We estimated covariate‐adjusted associations of loge‐transformed urinary methyl, propyl, and butyl paraben concentrations (individually using linear regression models and as a mixture using quantile g‐computation) collected prior to conception and during pregnancy with Behavioral Assessment System for Children‐3 and Behavior Rating Inventory of Executive Function T‐scores (higher scores indicate more problem behaviors).This analysis included 140 mothers, 81 fathers, and 171 children (25 sets of twins); parents were predominantly non‐Hispanic white (88% for both mothers and fathers). In single paraben models, higher paternal preconception urinary propyl and methyl paraben concentrations were associated with higher Internalizing Problem T‐scores (propyl paraben β$\beta \;$= 1.7; 95% confidence interval: 0.6, 2.8, methyl paraben β$\beta \;$= 2.2; 95% confidence interval: 0.5, 3.9) and higher Behavioral Symptom Index T‐scores (propyl paraben β$\beta \;$= 1.4; 95% confidence interval: 0.3, 2.5, methyl paraben β$\beta \;$= 1.6; 95% confidence interval: ‐0.1, 3.3). Each quantile increase in the paternal mixture of three parabens was associated with a 3.4 (95% confidence interval: 0.67, 6.1) and 2.5 (95% confidence interval: 0.01, 5.0) increased internalizing problem and Behavioral Symptom Index T‐scores respectively. Higher paternal preconception (β$\beta \;$= 1.0; 95% confidence interval: 0.04, 1.9) and maternal preconception (β$\beta \;$= 1.1 95% confidence interval: ‐0.1, 2.2) concentrations of propyl paraben were associated with higher Behavior Rating Inventory of Executive Function Metacognition Index T‐scores in children, but the paraben mixtures was not.In this cohort, paternal preconception urinary concentrations of propyl and methyl paraben were associated with worse parent‐reported child behaviors. [ABSTRACT FROM AUTHOR]

Postnatal antiretroviral (ARV) prophylaxis for infants born to women with HIV is a critical component of perinatal HIV transmission prevention. However, variability in prophylaxis regimens remains and consistency with guidelines has not been evaluated in the United States. We evaluated trends over time in prophylaxis regimens among 6386 HIV-exposed uninfected (HEU) infants using pooled data spanning two decades from three US-based cohorts: the Women and Infants Transmission Study (WITS, 1990-2007), Pediatric AIDS Clinical Trials Group (PACTG) 219C (1993-2007), and the PHACS Surveillance Monitoring of ART Toxicities (SMARTT) study (2007-2015). We also identified maternal and infant risk factors for use of combination prophylaxis regimens (≥2 ARVs) and examined consistency with US perinatal guidelines. We found that receipt of combination prophylaxis between 1996 and 2015 ranged from 2% to 15%, with a consistent median duration of 6 weeks. Infants whose mothers had lower CD4 T-cell counts, higher viral load (VL), no antepartum ARVs, age <20 years at delivery, and Cesarean delivery had significantly higher rates of combination prophylaxis, while infants born 2006-2010 (vs. 2011-2015), who were Hispanic or with lower maternal education levels, had significantly lower rates. Predictors for combination prophylaxis varied over time, with the strongest associations of maternal VL in later birth cohorts. While use of combination prophylaxis increased over time, only 50% of high-risk infants received such regimens in 2011-2015. In conclusion, HEU infants at higher risk of HIV acquisition are more likely to receive combination neonatal prophylaxis, consistent with US guidelines. However, substantial variability remains, and infants at higher risk often fail to receive combination prophylaxis. [ABSTRACT FROM AUTHOR]

Background Childhood blood lead levels (BLL) have been associated with growth impairment. Objectives We assessed associations of peripubertal BLL with adolescent growth and near adult height in a longitudinal cohort of Russian boys. Methods 481 boys were enrolled at ages 8–9 years and followed annually to age 18. At enrollment, BLL was measured, and height, weight, and pubertal staging were obtained annually during 10 years of follow-up. Mixed effects models were used to assess the associations of BLL with longitudinal age-adjusted World Health Organization Z -scores for height (HT- Z ) and body mass index (BMI- Z ), and annual height velocity (HV). Interactions between boys' age and BLL on growth outcomes were evaluated. Results The median (range) BLL was 3.0 (0.5–31.0) μg/dL. At age 18 years, 79% of boys had achieved near adult height (HV < 1.0 cm/year), and means (SD) for HT- Z and BMI- Z were 0.15 (0.92) and − 0.32 (1.24). Over 10 years of follow-up, after covariate adjustment, boys with higher (≥ 5 μg/dL) BLL compared with lower BLL were shorter (adjusted mean difference in HT- Z = − 0.43, 95% CI − 0.60, − 0.25, p -value < 0.001), translating to a 2.5 cm lower height at age 18 years. The decrement in height for boys with higher BLL was most pronounced at 12 to 15 years of age (interaction p = 0.03). Boys with higher BLL were leaner (adjusted mean difference in BMI- Z = − 0.22, 95% CI: − 0.45, 0.01, p = 0.06). Conclusions Higher peripubertal BLLs were associated with shorter height through age 18 years, suggesting a persistent effect of lead on linear growth. [ABSTRACT FROM AUTHOR]

Despite improved survival due to combination antiretroviral therapy (cART), youth with perinatally-acquired HIV (PHIV) show cognitive deficits and developmental delay at increased rates. HIV affects the brain during critical periods of development, and the brain may be a persistent reservoir for HIV due to suboptimal blood brain barrier penetration of cART. We conducted structural magnetic resonance imaging (sMRI) and cognitive testing in 40 PHIV youth (mean age = 16.7 years) recruited from the NIH Pediatric HIV/AIDS Cohort Study (PHACS) who are part of the first generation of PHIV youth surviving into adulthood. Historical and current HIV disease severity and substance use measures were also collected. Total and regional cortical grey matter brain volumes were compared to a group of 334 typically-developing, HIV-unexposed and uninfected youth (frequency-matched for age and sex) from the Pediatric Imaging, Neurocognition, and Genetics (PING) study (mean age = 16.1 years). PHIV youth had smaller (2.8-5.1%) total and regional grey matter volumes than HIV-unexposed and uninfected youth, with smallest volumes seen among PHIV youth with higher past peak viral load (VL) and recent unsuppressed VL. In PHIV youth, worse cognitive performance correlated with smaller volumes. This pattern of smaller grey matter volumes suggests that PHIV infection may influence brain development and underlie cognitive dysfunction seen in this population. Among PHIV youth, smaller volumes were also linked to substance use (alcohol use: 9.0-13.4%; marijuana use: 10.1-16.0%). In this study, collection of substance use information was limited to the PHIV cohort; future studies should also collect substance use information in controls to further address interactions between HIV and substance use on brain volume. [ABSTRACT FROM AUTHOR]

Midlife in women is an understudied time for environmental chemical exposures and menopausal outcomes. Recent cross-sectional research links phthalates with hot flashes, but little is known regarding such associations over time. Our objective was to estimate longitudinal associations between repeated measures of urinary phthalate metabolite concentrations and hot flash outcomes in midlife women. Using data from the Midlife Women's Health Study (MWHS), a prospective longitudinal study, we fit generalized linear mixed-effects models (GLMMs) and Cox proportional hazards regression models to repeated measures over a 4-year period. Recruitment occurred in Baltimore and surrounding counties, Maryland, USA between 2006 and 2015. Participants were premenopausal/perimenopausal women (n = 744) aged 45–54 years, who were not pregnant, not taking menopausal symptom medication or oral contraceptives, did not have hysterectomy/oophorectomy, and irrespective of hot flash experience. Baseline mean (SD) age was 48.4 (2.45), and 65% were premenopausal. Main outcome measures included adjusted odds ratios (ORs) for 4 self-reported hot flash outcomes (ever experienced, past 30 days experience, weekly/daily, and moderate/severe), and hazard ratios (HRs) for incident hot flashes. We observed mostly increased odds of certain hot flash outcomes with higher concentrations of metabolites of di (2-ethylhexyl) phthalate (DEHP), monoisobutyl phthalate (MiBP), and a molar summary measure of plasticizer phthalate metabolites (DEHP metabolites, mono-(3-carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP)). Some associations between exposures and outcomes indicated decreased odds. In conclusion, phthalate metabolites were associated with certain hot flash outcomes in midlife women. Midlife may be a sensitive period for higher phthalate metabolite concentrations with respect to menopausal symptoms. • Data on associations of urinary phthalate metabolites with hot flashes are scarce. • We estimated associations across 4 years of the Midlife Women's Health Study. • Outcomes were hot flash experience, recency, frequency, severity, and incidence. • Some urinary phthalate metabolite levels were associated with hot flash outcomes. • Higher concentrations were mostly associated with higher odds of hot flash outcomes. [ABSTRACT FROM AUTHOR]

Physical activity could benefit reproductive function through its ability to regulate energy balance and improve insulin sensitivity, but its association with IVF outcomes remains unclear. The aim of this study was to evaluate whether pre-treatment physical and sedentary activity is associated with outcomes of IVF. The Environment and Reproductive Health Study is an ongoing prospective cohort study that enrols subfertile couples at Massachusetts General Hospital Fertility Center. Time spent in physical and sedentary activities in the year before IVF treatment is self-reported using a validated questionnaire. This analysis included 273 women who underwent 427 IVF cycles. Women engaged in a median of 2.8 h per week of moderate-to-vigorous activities. Time spent in moderate-to-vigorous physical activities and total metabolic equivalent task hours before IVF were not associated with probability of implantation, clinical pregnancy or live birth. Of the specific physical activities, only greater time spent in aerobics, rowing, and on the ski or stair machine was associated with higher probability of live birth. Time spent in total and specific sedentary activities were not associated with clinical outcomes of IVF. Physical activity is unlikely to have a deleterious effect on IVF success and certain forms of vigorous activity may be beneficial. [ABSTRACT FROM AUTHOR]

Background. Combination antiretroviral therapy (cART) has resulted in a dramatic decrease in human immunodeficiency virus (HIV)-related opportunistic infections and deaths in US youth, but both continue to occur. Methods. We estimated the incidence of complications and deaths in IMPAACT P1074, a long-term US-based prospective multicenter cohort study conducted from April 2008 to June 2014. Incidence rates of selected diagnoses and trends over time were compared with those from a previous observational cohort study, P219C (2004-2007). Causes of death and relevant demographic and clinical features were reviewed. Results. Among 1201 HIV-infected youth in P1074 (87% perinatally infected; mean [standard deviation] age at last chart review, 20.9 [5.4] years), psychiatric and neurodevelopmental disorders, asthma, pneumonia, and genital tract infections were among the most common comorbid conditions. Compared with findings in P219C, conditions with significantly increased incidence included substance or alcohol abuse, latent tuberculosis, diabetes mellitus, atypical mycobacterial infections, vitamin D deficiency or metabolic bone disorders, anxiety disorders, and fractures; the incidence of pneumonia decreased significantly. Twenty-eight deaths occurred, yielding a standardized mortality rate 31.5 times that of the US population. Those who died were older, less likely to be receiving cART, and had lower CD4 cell counts and higher viral loads. Most deaths (86%) were due to HIV-related medical conditions. Conclusions. Opportunistic infections and deaths are less common among HIV-infected youth in the US in the cART era, but the mortality rate remains elevated. Deaths were associated with poor HIV control and older age. Emerging complications, such as psychiatric, inflammatory, metabolic, and genital tract diseases, need to be addressed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Few human studies have evaluated the impact of childhood exposure to organochlorine pesticides (OCP) on pubertal development. OBJECTIVE.: We evaluated associations of serum OCP concentrations [hexachlorobenzene (HCB), [β-hexachlorocyclohexane βHCH), and p,p-dichlorodiphenyldichloroethylene (p,p'-DDE)] with age at attainment of sexual maturity among boys. METHODS: From 2003 through 2005, 350 8- to 9-year-old boys from Chapaevsk, Russia, with measured OCPs were enrolled and followed annually for 8 years. We used multivariable interval-censored models to evaluate associations of OCPs (quartiles) with three physician-assessed measures of sexual maturity: Tanner stage 5 for genitalia growth, Tanner stage 5 for pubic hair growth, or testicular volume (TV) ≥ 20 mL in either testis. RESULTS: In adjusted models, boys with higher HCB concentrations achieved sexual maturity reflected by TV ≥ 20 mL a mean of 3.1 months (95% CI: -1.7, 7.8), 5.3 months (95% CI: 0.6, 10.1), and 5.0 months (95% CI: 0.2, 9.8) later for quartiles Q2, Q3, and Q4, respectively, compared with Q1 (p trend = 0.04). Tanner stage 5 for genitalia growth was attained a mean of 2.2 months (95% CI: -3.1, 7.5), 5.7 months (95% CI: 0.4, 11.0), and 3.7 months (95% CI: -1.7, 9.1) later for quartiles Q2, Q3, and Q4, respectively, of βHCH compared with Q1 (p trend = 0.09). Tanner stage 5 for pubic hair growth occurred 6-9 months later on average for boys in the highest versus lowest quartile for HCB (p trend < 0.001), βHCH (trend p = 0.01), and p, p'-DDE (p trend = 0.04). No associations were observed between p, p' -DDE and Tanner stage 5 for genitalia growth or TV ≥ 20 mL. CONCLUSIONS AND RELEVANCE: Higher prepubertal serum HCB and βHCH concentrations were associated with a later age at attainment of sexual maturity. Only the highest quartile of serum p, p'-DDE was associated with later pubic hair maturation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Human exposure to phenols, including bisphenol A and parabens, is widespread. Evidence suggests that paternal exposure to environmental chemicals may adversely affect reproductive outcomes. OBJECTIVES: We evaluated associations of paternal phenol urinary concentrations with fertilization rate, embryo quality, implantation, and live birth. METHODS: Male--female couples who underwent in vitro fertilization (IVF) and/or intrauterine insemination (IUI) cycles in a prospective study of environmental determinants of fertility and pregnancy outcomes were included. The geometric mean of males' specific gravity--adjusted urinary phenol concentrations measured before females' cycle was quantified. Associations between male urinary phenol concentrations and fertilization rate, embryo quality, implantation, and live birth were investigated using generalized linear mixed models to account for multiple cycles per couple. RESULTS: Couples (n = 218) underwent 195 IUI and 211 IVF cycles. Paternal phenol concentrations were not associated with fertilization or live birth following IVF. In adjusted models, compared with the lowest quartile of methyl paraben, paternal concentrations in the second quartile were associated with decreased odds of live birth following IUI (adjusted odds ratio = 0.19; 95% CI: 0.04, 0.82). CONCLUSIONS: TO our knowledge, these are some of the first data on the association of paternal urinary phenol concentrations with reproduction and pregnancy outcomes. Although these results do not preclude possible adverse effects of paternal paraben exposures on such outcomes, given the modest sample size, further understanding could result from confirmation using a larger and more diverse population. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies have reported acute (hours-28 days) associations between ambient ultrafine particles (UFP; diameter <0.1) and biomarkers of cardiovascular health using central site data We evaluated particle number concentration (a proxy measure for UFP) measured at a central site a local near-highway site and predicted residential concentrations with response of biomarkers of inflammation and coagulation in a near-highway population. Methods: Participants provided two blood samples for analysis of interleukin-6 (IL-6) high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-a receptor II, and fibrinogen. Mixed effect models were used to evaluate the association between PNC levels on the same day, prior 2 days, and moving averages of 3 to 28 days Results: Estimated effects on biomarkers of a 5000 unit increase in central site PNC generally increased with longer averaging times for IL-6, hs-CRP, and fibrinogen. Effect estimates were highest for a 28-day moving average, with 91% (95% confidence interval [Cl]: 9, 230) higher IL-6 levels, 74% (95% Cl: -7 220) higher hs-CRP levels, and 59% (95% Cl: -13, 130) higher fibrinogen levels. We observed no clear trend between near-highway or predicted residential PNC and any of the biomarkers Conclusions: Only central site PNC increased blood markers of inflammation while near-highway and predicted residential values did not. We cannot fully explain this result, although differing PNC composition is a possibility. Future studies would assist in understanding these findings. [ABSTRACT FROM AUTHOR]

Background In animal studies, organochlorine pesticide (OCP) exposure alters pubertal development; however, epidemiological data are limited and inconsistent. Objective To evaluate the associations of serum OCP concentrations [hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), and p , p ′-dichlorodiphenyldichloroethylene ( p , p ′-DDE)] with male pubertal onset. Methods In Chapaevsk, Russia, a town environmentally contaminated with OCPs, 350 8–9 year old boys with measured OCPs were enrolled during 2003–2005 and were followed annually for eight years. We evaluated three measures of pubertal onset: testicular volume (TV) > 3 mL in either testis, or stage 2 or greater for genitalia (G2 +), or pubic hair (P2 +). We used multivariable interval-censored models to evaluate associations of OCPs (quartiles) with physician-assessed pubertal onset. Results In adjusted models, boys with higher HCB concentrations had later mean ages of TV > 3 mL and P2+ (but not G2+). Mean age at attaining TV > 3 mL was delayed 3.6 (95% CI: − 2.6, 9.7), 7.9 (95% CI: 1.7, 14.0), and 4.7 months (95% CI: − 1.4, 10.9) for HCB Q2, Q3, and Q4, respectively, compared to Q1 (trend p: 0.06). Boys with higher HCB concentrations reached P2+ 0.1 months earlier (95% CI: − 5.8, 5.6) for Q2, 4.7 months later (95% CI: − 1.0, 10.3) for Q3 and 4.6 months later (95% CI: − 1.1, 10.3) for Q4 compared to Q1 (trend p: 0.04). There were no associations of serum β-HCH and p , p ′-DDE concentrations with age of pubertal onset. Conclusion Higher prepubertal serum HCB concentrations were associated with later age of gonadarche and pubarche. [ABSTRACT FROM AUTHOR]

Organochlorine pesticides (OCPs) have been linked to adult metabolic disorders; however, few studies have examined these associations in childhood. We prospectively evaluated the associations of baseline serum OCPs (hexachlorobenzene, β-hexachlorocyclohexane, and p,p′-dichlorodiphenyldichloroethylene) in Russian boys with subsequent repeated measurements of serum glucose, insulin, lipids, leptin, and calculated homeostatic model assessment of insulin resistance (IR). During 2003–2005, we enrolled 499 boys aged 8–9 years in a prospective cohort; 318 had baseline serum OCPs and serum biomarkers measured at ages 10–13 years. Multivariable generalized estimating equation and mediation regression models were used to examine associations and direct and indirect (via body mass index (BMI) (weight (kg)/height (m)2)) effects of prepubertal OCP tertiles and quintiles with biomarkers. In multivariable models, higher p,p′-dichlorodiphenyldichloroethylene (quintile 5 vs. quintile 1) was associated with lower leptin, with relative mean decreases of 61.8% (95% confidence interval: 48.4%, 71.7%) in models unadjusted for BMI and 22.2% (95% confidence interval: 7.1%, 34.9%) in models adjusted for BMI; the direct effect of p,p′-dichlorodiphenyldichloroethylene on leptin accounted for 27% of the total effect. IR prevalence was 6.6% at ages 12–13 years. Higher hexachlorobenzene (tertile 3 vs. tertile 1) was associated with higher odds of IR in models adjusted for BMI (odds ratio = 4.37, 95% confidence interval: 1.44, 13.28). These results suggest that childhood OCPs may be associated with IR and lower leptin. [ABSTRACT FROM PUBLISHER]

In vitro fertilization (IVF) is an increasingly common method of assisted reproductive technology. Because of the careful observation and follow-up required as part of the procedure, IVF studies provide an ideal opportunity to identify and assess clinical and demographic factors along with environmental exposures that may impact successful reproduction. A major challenge in analyzing data from IVF studies is handling the complexity and multiplicity of outcome, resulting from both multiple opportunities for pregnancy loss within a single IVF cycle in addition to multiple IVF cycles. To date, most evaluations of IVF studies do not make use of full data because of its complex structure. In this paper, we develop statistical methodology for analysis of IVF data with multiple cycles and possibly multiple failure types observed for each individual. We develop a general analysis framework based on a generalized linear modeling formulation that allows implementation of various types of models including shared frailty models, failure-specific frailty models, and transitional models, using standard software. We apply our methodology to data from an IVF study conducted at the Brigham and Women's Hospital, Massachusetts. We also summarize the performance of our proposed methods on the basis of a simulation study. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Highlights: [•] An in vivo human model looking at the underlying mechanism for BPA's action at the target tissue. [•] Translational pilot study on a subsample of a larger IVF cohort. [•] Possible non-monotonic dose–response association between BPA and Cyp19 gene expression in human ovarian granulosa cells. [Copyright &y& Elsevier]

Background: Few studies have evaluated predictors of childhood exposure to organochlorine pesticides (OCPs), a class of lipophilic persistent chemicals. Objectives: Our goal was to identify predictors of serum OCP concentrations--hexachloro-benzene (HCB), β-hexachlorocyclohexane (β-HCH), and p,p-dichlorodiphenyldichloroethylene (p,p' DDE)--among boys in Chapaevsk, Russia. Methods: Between 2003 and 2005, 499 boys 8-9 years of age were recruited in a prospective cohort. The initial study visit included a physical examination; blood collection; health, lifestyle, and food-frequency questionnaires; and determination of residential distance from a local factory complex that produced HCB and β-HCH. Fasting serum samples were analyzed for OCPs at the U.S. Centers for Disease Control and Prevention. General linear regression models were used to identify predictors of the boys’ serum HCB, β-HCH, and p,p´ DDE concentrations. Results: Among 355 boys with OCP measurements, median serum HCB, β-HCH, and p,p´ DDE concentrations were 158, 167, and 284 ng/g lipid, respectively. Lower body mass index, longer breastfeeding duration, and local dairy consumption were associated with higher concentrations of OCPs. Boys who lived < 2 km from the factory complex had 64% (95% CI: 37, 96) and 57% (95% CI: 32, 87) higher mean HCB and β-HCH concentrations, respectively, than boys who lived ≥ 5 km away. Living > 3 years in Chapaevsk predicted higher β-HCH concentrations, and having parents who lacked a high school education predicted higher p,p´ DDE concentrations. Conclusions: Among this cohort of prepubertal Russian boys, predictors of serum OCPs included consumption of local dairy products, longer local residence, and residential proximity to the local factory complex. [ABSTRACT FROM AUTHOR]

Obtaining accurate estimates of mental health problems among youth perinatally infected with HIV (PHIV) helps clinicians develop targeted interventions but requires enrollment and retention of representative youth into research studies.The study design for IMPAACT P1055, a US-based, multisite prospective study of psychiatric symptoms among PHIV youth and uninfected controls aged 6 to 17 years old, is described. Participants were compared with nonparticipants by demographic characteristics and reasons were summarized for study refusal. Adjusted logistic regression models were used to evaluate the association of psychiatric symptoms and other factors with loss to follow-up (LTFU).Among 2281 youth screened between 2005 and 2006 at 29 IMPAACT research sites, 580 (25%) refused to participate, primarily because of time constraints. Among 1162 eligible youth approached, 582 (50%) enrolled (323 PHIV and 259 Control), with higher participation rates for Hispanic youth. Retention at 2 years was significantly higher for PHIV than Controls (84% vs 77%, P = 0.03). In logistic regression models adjusting for sociodemographic characteristics and HIV status, youth with any self-assessed psychiatric condition had higher odds of LTFU compared with those with no disorder (adjusted odds ratio = 1.56, 95% confidence interval: 1.00 to 2.43). Among PHIV youth, those with any psychiatric condition had 3-fold higher odds of LTFU (adjusted odds ratio = 3.11, 95% confidence interval: 1.61 to 6.01).Enrollment and retention of PHIV youth into mental health research studies is challenging for those with psychiatric conditions and may lead to underestimated risks for mental health problems. Creative approaches for engaging HIV-infected youth and their families are required for ensuring representative study populations. [ABSTRACT FROM AUTHOR]

Background Central nervous system (CNS) vasculopathy has been reported in human immunodeficiency virus–infected (HIV+) adults and children. In children, it often presents with HIV encephalopathy, stroke, or intracerebral aneurysms. The etiology, incidence, and risk factors of HIV-associated CNS vasculopathy in children are unknown. Methods We identified HIV+ children with a diagnosis of vasculopathy or other cerebrovascular events among children enrolled between 1993 and 2004 in 2 prospective, multicenter cohort studies. Demographic and laboratory data, history of antiretroviral use, and signs, symptoms, and diagnostic studies pertaining to the CNS event were reviewed. Results Among the 3338 HIV+ children, 51 had diagnoses that suggested CNS vasculopathy. Of these, 12 (24%) were included in this analysis, after excluding those with alternative diagnoses and those from closed sites. Among these 12, 4 (33%) were female, 4 (33%) were white, and 10 (83%) had perinatal HIV. Their average age at the event was 10.8 years with a median CD4 count of 22 cells/mm3 and median HIV-1 viral load of 94 304 copies/mL. Fifty-eight percent of subjects had a history of opportunistic infections before the CNS event. Fifty percent had cerebral aneurysms on imaging. The overall incidence among HIV+ subjects was 3.4 cases per 10 000 person-years (95% confidence interval, 1.8–6.0). Conclusions CNS vasculopathy in HIV+ children is uncommon but more common than in the general pediatric population. Cerebral aneurysms are the most common manifestation. Although the pathogenesis remains unclear, older children and those with low CD4 counts and high HIV viral loads are at the highest risk. [ABSTRACT FROM AUTHOR]

Background. Use of antiretroviral drugs (ARVs) during pregnancy has been associated with higher risk of preterm birth.Methods. The Pediatric HIV/AIDS Cohort Study network's Surveillance Monitoring for ART Toxicities study is a US-based cohort of human immunodeficiency virus (HIV)–exposed uninfected children. We evaluated maternal ARV use during pregnancy and the risk of any type of preterm birth (ie, birth before 37 completed weeks of gestation), the risk of spontaneous preterm birth (ie, preterm birth that occurred after preterm labor or membrane rupture, without other complications), and the risk of small for gestational age (SGA; ie, a birth weight of <10th percentile for gestational age). Multivariable logistic regression models were used to evaluate the association of ARVs and timing of exposure, while adjusting for maternal characteristics.Results. Among 1869 singleton births, 18.6% were preterm, 10.2% were spontaneous preterm, and 7.3% were SGA. A total of 89% used 3-drug combination ARV regimens during pregnancy. In adjusted models, the odds of preterm birth and spontaneous preterm birth were significantly greater among mothers who used protease inhibitors during the first trimester (adjusted odds ratios, 1.55 and 1.59, respectively) but not among mothers who used nonnucleoside reverse-transcriptase inhibitor or triple-nucleoside regimens during the first trimester. Combination ARV exposure starting later in pregnancy was not associated with increased risk. No associations were observed between SGA and exposure to combination ARV regimens.Conclusions. Protease inhibitor use early in pregnancy may be associated with increased risk for prematurity. [ABSTRACT FROM AUTHOR]

STUDY QUESTION In women undergoing IVF, are urinary bisphenol A (BPA) concentrations associated with ovarian response and early reproductive outcomes, including oocyte maturation and fertilization, Day 3 embryo quality and blastocyst formation? SUMMARY ANSWER Higher urinary BPA concentrations were found to be associated with decreased ovarian response, number of fertilized oocytes and decreased blastocyst formation. WHAT IS KNOWN ALREADY Experimental animal and in vitro studies have reported associations between BPA exposure and adverse reproductive outcomes. We previously reported an association between urinary BPA and decreased ovarian response [peak serum estradiol (E2) and oocyte count at the time of retrieval] in women undergoing IVF; however, there are limited human data on reproductive health outcomes, such as fertilization and embryo development. STUDY DESIGN, SIZE AND DURATION Prospective preconception cohort study. One hundred and seventy-four women aged 18–45 years and undergoing 237 IVF cycles were recruited at the Massachusetts General Hospital Fertility Center, Boston, MA, USA, between November 2004 and August 2010. These women were followed until they either had a live birth or discontinued treatment. Cryothaw and donor egg cycles were not included in the analysis. PARTICIPANTS/MATERIALS, SETTINGAND METHODS Urinary BPA concentrations were measured by online solid-phase extraction-high-performance liquid chromatography-isotope dilution-tandem mass spectrometry. Mixed effect models, poisson regression and multivariate logistic regression models were used wherever appropriate to evaluate the association between cycle-specific urinary BPA concentrations and measures of ovarian response, oocyte maturation (metaphase II), fertilization, embryo quality and cleavage rate. We accounted for correlation among multiple IVF cycles in the same woman using generalized estimating equations. MAIN RESULTS AND THE ROLE OF CHANCE The geometric mean (SD) for urinary BPA concentrations was 1.50 (2.22) µg/l. After adjustment for age and other potential confounders (Day 3 serum FSH, smoking, BMI), there was a significant linear dose–response association between increased urinary BPA concentrations and decreased number of oocytes (overall and mature), decreased number of normally fertilized oocytes and decreased E2 levels (mean decreases of 40, 253 and 471 pg/ml for urinary BPA quartiles 2, 3 and 4, when compared with the lowest quartile, respectively; P-value for trend = 0.001). The mean number of oocytes and normally fertilized oocytes decreased by 24 and 27%, respectively, for the highest versus the lowest quartile of urinary BPA (trend test P < 0.001 and 0.002, respectively). Women with urinary BPA above the lowest quartile had decreased blastocyst formation (trend test P-value = 0.08). LIMITATIONS AND REASONS FOR CAUTION Potential limitations include exposure misclassification due to the very short half-life of BPA and its high variability over time; uncertainty about the generalizability of the results to the general population of women conceiving naturally and limited sample. WIDER IMPLICATIONS OF THE FINDINGS The results from this extended study, using IVF as a model to study early reproductive health outcomes in humans, indicate a negative dose–response association between urinary BPA concentrations and serum peak E2 and oocyte yield, confirming our previous findings. In addition, we found significantly decreased metaphase II oocyte count and number of normally fertilizing oocytes and a suggestive association between BPA urinary concentrations and decreased blastocyst formation, thus indicating that BPA may alter reproductive function in susceptible women undergoing IVF. STUDY FUNDING/COMPETING INTEREST(S) This work was supported ... [ABSTRACT FROM PUBLISHER]

Purpose: To investigate whether history of comorbidities is associated with markers of ovarian reserve among subfertile women. Methods: This observational study includes 645 women seeking fertility care at the Massachusetts General Hospital who enrolled in the Environment and Reproductive Health (EARTH) study (2005–2019). Women completed a comprehensive questionnaire including medical diagnosis of comorbidities. Ovarian reserve markers including antral follicle count (AFC), assessed by transvaginal ultrasound, and circulating serum levels of day 3 FSH and AMH, are assessed by immunoassays. We fit linear regression models to evaluate the association between history of comorbidities and markers of ovarian reserve while adjusting for confounders. Results: Self-reported history of hypertension, cancer, and neurological disorders was negatively associated with AFC in unadjusted models and in adjusted models for age, smoking, physical activity, comorbidity count, and BMI. Adjusted mean AFC (95% CI) was lower among women with history of hypertension, compared to women with no self-reported history of hypertension (11.5 vs 15.6, p value 0.0001). In contrast, day 3 FSH levels were positively related to history of eating disorders in both unadjusted and adjusted models (10.8 vs. 7.43 IU/L, p value ≤ 0.0001). Self-reported history of other comorbidities was unrelated to AFC, day 3 FSH, and AMH levels. Conclusions: History of hypertension, cancer, and neurological disorders was negatively associated with AFC, and eating disorders were positively related to day 3 FSH levels. The prevention of common comorbidities among women in reproductive age may help increase women's fertility given the declining birth rates and increasing use of assisted reproductive technologies in the past years. [ABSTRACT FROM AUTHOR]

Background: Bisphenol A (BPA) is a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins found in numerous consumer products. In experimental animals, BPA increases embryo implantation failure and reduces litter size. Objective: We evaluated the association of urinary BPA concentrations with implantation failure among women undergoing in vitro fertilization (IVF). Methods: We used online solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry to measure urinary BPA concentrations in 137 women in a prospective cohort study among women undergoing IVF at the Massachusetts General Hospital Fertility Center in Boston, Massachusetts. We used logistic regression to evaluate the association of cycle-specific urinary BPA concentrations with implantation failure, accounting for correlation among multiple IVF cycles in the same woman using generalized estimating equations. Implantation failure was defined as a negative serum β-human chorionic gonadotropin test (β-hCG < 6 IU/L) 17 days after egg retrieval. Results: Among 137 women undergoing 180 IVF cycles, urinary BPA concentrations had a geometric mean (SD) of 1.53 (2.22) µg/L. Overall, 42% (n = 75) of the IVF cycles resulted in implantation failure. In adjusted models, there was an increased odds of implantation failure with higher quartiles of urinary BPA concentrations {odds ratio (OR) 1.02 [95% confidence interval (CI): 0.35, 2.95}, 1.60 (95% CI: 0.70, 3.78), and 2.11 (95% CI: 0.84, 5.31) for quartiles 2, 3, and 4, respectively, compared with the lowest quartile (p-trend = 0.06). Conclusion: There was a positive linear dose-response association between BPA urinary concentrations and implantation failure. [ABSTRACT FROM AUTHOR]

The Pediatric HIV/AIDS Cohort Study’s Surveillance Monitoring of ART Toxicities Study is a prospective cohort study conducted at 22 US sites between 2007 and 2011 that was designed to evaluate the safety of in utero antiretroviral drug exposure in children not infected with human immunodeficiency virus who were born to mothers who were infected. This ongoing study uses a “trigger-based” design; that is, initial assessments are conducted on all children, and only those meeting certain thresholds or “triggers” undergo more intensive evaluations to determine whether they have had an adverse event (AE). The authors present the estimated rates of AEs for each domain of interest in the Surveillance Monitoring of ART Toxicities Study. They also evaluated the efficiency of this trigger-based design for estimating AE rates and for testing associations between in utero exposures to antiretroviral drugs and AEs. The authors demonstrate that estimated AE rates from the trigger-based design are unbiased after correction for the sensitivity of the trigger for identifying AEs. Even without correcting for bias based on trigger sensitivity, the trigger approach is generally more efficient for estimating AE rates than is evaluating a random sample of the same size. Minor losses in efficiency when comparing AE rates between persons exposed and unexposed in utero to particular antiretroviral drugs or drug classes were observed under most scenarios. [ABSTRACT FROM PUBLISHER]

Background: Chromosomal abnormalities contribute substantially to reproductive problems, but the role of environmental risk factors has received little attention. Objectives: We evaluated the association of polychlorinated biphenyl (PCB) and dichlorodiphenyldichloroethylene (p,p′-DDE) exposures with sperm sex-chromosome disomy. Methods: We conducted a cross-sectional study of 192 men from subfertile couples. We used multiprobe fluorescence in situ hybridization (FISH) for chromosomes X, Y, and 18 to determine XX, YY, XY, and total sex-chromosome disomy in sperm nuclei. Serum was analyzed for concentrations of 57 PCB congeners and p,p′-DDE. Poisson regression models were used to calculate incidence rate ratios (IRRs) for disomy by exposure quartiles, controlling for demographic characteristics and semen parameters. Results: The median percent disomy was 0.3 for XX and YY, 0.9 for XY, and 1.6 for total sex-chromosome disomy. We observed a significant trend of increasing IRRs for increasing quartiles of p,p′-DDE in XX, XY, and total sex-chromosome disomy, and a significant trend of increasing IRRs for increasing quartiles of PCBs for XY and total sex-chromosome disomy; however, there was a significant inverse association for XX disomy. Conclusions: Our findings suggest that exposure to p,p′-DDE may be associated with increased rates of XX, XY, and total sex-chromosome disomy, whereas exposure to PCBs may be associated with increased rates of YY, XY, and total sex-chromosome disomy. In addition, we observed an inverse association between increased exposure to PCBs and XX disomy. Further work is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Chromosomal abnormalities contribute substantially to reproductive problems, but the role of environmental risk factors has received little attention. Objectives: We evaluated the association of polychlorinated biphenyl (PCB) and dichlorodiphenyldichloroethylene (p,p′-DDE) exposures with sperm sex-chromosome disomy. Methods: We conducted a cross-sectional study of 192 men from subfertile couples. We used multiprobe fluorescence in situ hybridization (FISH) for chromosomes X, Y, and 18 to determine XX, YY, XY, and total sex-chromosome disomy in sperm nuclei. Serum was analyzed for concentrations of 57 PCB congeners and p,p′-DDE. Poisson regression models were used to calculate incidence rate ratios (IRRs) for disomy by exposure quartiles, controlling for demographic characteristics and semen parameters. Results: The median percent disomy was 0.3 for XX and YY, 0.9 for XY, and 1.6 for total sex-chromosome disomy. We observed a significant trend of increasing IRRs for increasing quartiles of p,p′-DDE in XX, XY, and total sex-chromosome disomy, and a significant trend of increasing IRRs for increasing quartiles of PCBs for XY and total sex-chromosome disomy; however, there was a significant inverse association for XX disomy. Conclusions: Our findings suggest that exposure to p,p′-DDE may be associated with increased rates of XX, XY, and total sex-chromosome disomy, whereas exposure to PCBs may be associated with increased rates of YY, XY, and total sex-chromosome disomy. In addition, we observed an inverse association between increased exposure to PCBs and XX disomy. Further work is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

BACKGROUND: Limited human data suggest an association of organochlorine pesticides (OCPs) with adverse effects on children's growth. OBJECTIVE: We evaluated the associations of OCPs with longitudinally assessed growth among peripubertal boys from a Russian cohort with high environmental OCP levels. METHODS: A cohort of 499 boys enrolled in the Russian Children's Study between 2003 and 2005 at 8-9 years of age were followed prospectively for 4 years. At study entry, 350 boys had serum OCPs measured. Physical examinations were conducted at entry and annually. The longitudinal associations of serum OCPs with annual measurements of body mass index (BMI), height, and height velocity were examined by multivariate mixed-effects regression models for repeated measures, controlling for potential confounders. RESULTS: Among the 350 boys with OCP measurements, median serum hexachlorobenzene (HCB), β-hexachlorocyclohexane (βHCH), and p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) concentrations were 159 ng/g lipid, 168 ng/g lipid, and 287 ng/g lipid, respectively. Age-adjusted BMI and height z-scores generally fell within the normal range per World Health Organization standards at entry and during follow-up. However, in adjusted models, boys with higher serum HCB, βHCH, and p,p′-DDE had significantly lower mean [95% confidence interval (CI)] BMI z-scores, by -0.84 (-1.23, -0.46), -1.32 (-1.70, -0.95), and -1.37 (-1.75, -0.98), respectively, for the highest versus lowest quintile. In addition, the highest quintile of p,p′-DDE was associated with a significantly lower mean (95% CI) height z-score, by -0.69 (-1.00, -0.39) than that of the lowest quintile. CONCLUSIONS: Serum OCP concentrations measured at 8-9 years of age were associated with reduced growth, particularly reduced BMI, during the peripubertal period, which may affect attainment of optimal adult body mass and height. [ABSTRACT FROM AUTHOR]

An increasing number of antiretroviral agents (ARVs) are approved for use, but their use during pregnancy in the United States has not been completely described. We used data from the Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring for ART Toxicities (SMARTT) study, a United States-based prospective cohort study of HIV-exposed but uninfected children, to assess temporal trends and maternal characteristics associated with the use of ARVs during pregnancy. The proportion of children exposed in utero to ARVs was calculated over time. A multivariable logistic regression model was used to estimate associations of maternal characteristics with use of highly active antiretroviral therapy (HAART) during pregnancy. We studied 1768 HIV-exposed but uninfected children born between 1995 and 2009 and enrolled in SMARTT. Prenatal HAART exposure increased from 19% in 1997 to 88% in 2009. Of children born in 2009, 99% had prenatal exposure to NRTIs (including zidovudine, 73%; lamivudine, 72%; tenofovir, 39%; and emtricitabine, 37%). Exposure to protease inhibitors increased from 15% in 1997 to 86% in 2009, while exposure to non-nucleoside reverse transcriptase inhibitors (NNRTIs) declined from 33% in 2003 to 11% in 2009. Higher maternal HIV RNA viral load (VL) concentration, lower maternal CD4 count, and earlier timing of the first maternal CD4 or VL measurement during pregnancy were associated with increased odds of HAART exposure. Prenatal HAART exposure has increased but is not universal. As ARV use during pregnancy continues to evolve, follow-up of children is needed to assess long-term effects of ARV exposures. [ABSTRACT FROM AUTHOR]

Dioxins, furans, and polychlorinated biphenyls (PCBs) are persistent and bioaccumulative toxic chemicals that are ubiquitous in the environment. We assessed predictors of their serum concentrations among women living in a Russian town contaminated by past industrial activity. Blood samples from 446 mothers aged 23-52 years were collected between 2003-2005 as part of the Russian Children's Study. Serum dioxin, furan, and PCB concentrations were quantified using high-resolution gas chromatography-mass spectrometry. Potential determinants of exposure were collected through interviews. Multivariate linear regression models were used to identify predictors of serum concentrations and toxic equivalencies (TEQs). The median total PCB concentrations and total TEQs were 260 ng/g lipid and 25 pg TEQ/g lipid, respectively. In multivariate analyses, both total PCB concentrations and total TEQs increased significantly with age, residential proximity to a local chemical plant, duration of local farming, and consumption of local beef. Both decreased with longer breastfeeding, recent increases in body mass index, and later blood draw date. These demographic and lifestyle predictors showed generally similar associations with the various measures of serum dioxins, furans, and PCBs. [ABSTRACT FROM AUTHOR]

Background: Although sources and routes of exposure to dioxins and polychlorinated biphenyls (PCBs) have been studied, information regarding exposure among children is limited. Breastfeeding and diet are two important contributors to early life exposure. To further understand other significant contributors to childhood exposure, we studied a cohort of children from a city with high environmental dioxin levels. Objectives: We investigated predictors of serum concentrations of polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzofurans (PCDFs)/co-planar PCBs (C-PCBs), toxic equivalents (TEQs), and PCBs among 8- to 9-year-old boys in Chapaevsk, Russia. Methods: We used general linear regression models to explore associations of log10-transformed serum concentrations of PCDDs/PCDFs/C-PCBs, TEQs, and PCBs at study entry with anthropometric, demographic, geographic, and dietary factors in 482 boys in Chapaevsk, Russia. Results: The median (25th, 75th percentile) concentration for total 2005 TEQs was 21.1 pg/g lipid (14.4, 33.2). Boys who were older, consumed local foods, were breast-fed longer, and whose mothers were employed at the Khimprom chemical plant (where chlorinated chemicals were produced) or gardened locally had significantly higher serum dioxins and PCBs, whereas boys with higher body mass index or more educated parents had significantly lower serum dioxins and PCBs. Boys who lived < 2 km from Khimprom had higher total TEQs (picograms per gram lipid) [adjusted mean = 30.6; 95% confidence interval (CI), 26.8-35.0] than boys who lived > 5 km away (adjusted mean = 18.8; 95% CI, 17.2-20.6). Conclusions: Our findings suggest that there are specific local sources of dioxin and PCB exposure among children in Chapaevsk including maternal gardening, consumption of locally grown food, and residential proximity to the Khimprom plant. [ABSTRACT FROM AUTHOR]

BACKGROUND. Little is known concerning the impact of HIV status disclosure on quality of life, leaving clinicians and families to rely on research of children with other terminal illnesses. OBJECTIVES. The purpose of this work was to examine the impact of HIV disclosure on pediatric quality of life and to describe the distribution of age at disclosure in a perinatally infected pediatric population. METHODS. A longitudinal analysis was conducted of perinatally HIV-infected youth ≥5 years of age enrolled in a prospective cohort study, Pediatric AIDS Clinical Trials Group 219C, with ≥1 study visit before and after HIV disclosure. Age-specific quality-of-life instruments were completed by primary caregivers at routine study visits. The distribution of age at disclosure was summarized. Six quality-of-life domains were assessed, including general health perception, symptom distress, psychological status, health care utilization, physical functioning, and social/role functioning. For each domain, mixed-effects models were fit to estimate the effect of disclosure on quality of life. RESULTS. A total of 395 children with 2423 study visits were analyzed (1317 predisclosure visits and 1106 postdisclosure visits). The median age at disclosure was estimated to be 11 years. Older age at disclosure was associated with earlier year of birth. Mean domain scores were not significantly different at the last undisclosed visit compared with the first disclosed visit, with the exception of general health perception. When all of the visits were considered, 5 of 6 mean domain scores were lower after disclosure, although the differences were not significant. In mixed-effects models, disclosure did not significantly impact quality of life for any domain. CONCLUSIONS. Age at disclosure decreased significantly over time. There were no statistically significant differences between predisclosure and postdisclosure quality of life; therefore, disclosure should be encouraged at an appropriate time. [ABSTRACT FROM AUTHOR]