Jane S. Burns

Association of blood lead levels with onset of puberty in Russian boys

Background Epidemiologic studies suggest a temporal trend of earlier onset and longer duration of puberty, raising concerns regarding the potential impact of environmental factors on pubertal development. Lead exposure has been associated with delayed pubertal onset in girls; however, epidemiologic data in boys are limited. Methods We used multivariable logistic regression models to explore the cross-sectional association of blood lead levels with growth and pubertal onset based on physician-assessed testicular volume (TV) and pubertal staging in 489 boys 8–9 years of age from Chapaevsk, Russia. We used multivariable linear regression models to assess associations of blood lead levels with somatic growth at the study entry visit. Results The median (25th–75th percentile) blood lead level was 3 μg/dL (2–5 μg/dL). Height, weight, body mass index, birth weight, and gestational age were predictive of the onset of puberty as assessed either by TV (> 3 mL), genitalia stage (G2), or both. Blood lead level was inversely associated with height (p < 0.001) and weight (p = 0.06) after adjustment for birth weight, gestational age, and age at examination. In multivariable adjusted analyses, boys with blood lead levels ≥ 5 μg/dL had 43% reduced odds of having entered G2 compared with those with lower levels (odds ratio = 0.57; 95% confidence interval, 0.34–0.95, p = 0.03). Conclusions Relatively low environmental blood lead levels were associated with decreased growth and differences in pubertal onset in periadolescent Russian boys. Future analyses of this prospective cohort will address pubertal onset and progression in relation to lead and other environmental chemicals.

Blood Lead Levels and Delayed Onset of Puberty in a Longitudinal Study of Russian Boys

OBJECTIVE: We evaluated the association of blood lead levels (BLLs) with pubertal onset in a longitudinal cohort of Russian boys. METHODS: A total of 489 Russian boys were enrolled in 2003–2005, at 8 to 9 years of age, and were monitored annually through May 2008. Cox proportional-hazards models were used to evaluate the association of BLLs at enrollment with time to pubertal onset during follow-up monitoring. RESULTS: A total of 481 boys had BLLs, with a median of 3 μg/dL and 28% with values of ≥5 μg/dL. The proportion of pubertal boys increased with age, from 12% at age 8 to 83% at age 12 for testicular volume of >3 mL, from 22% to 90% for genitalia stage 2 or higher, and from 4% to 40% for pubic hair stage 2 or higher. After adjustment for potential confounders including BMI and height, boys with high BLLs (≥5 μg/dL) had 24% to 31% reduced risk of pubertal onset, on the basis of testicular volume of >3 mL (hazard ratio [HR]: 0.73 [95% confidence interval [CI]: 0.55–0.97]; P = .03), genitalia staging (HR: 0.76 [95% CI: 0.59–0.98]; P = .04), and pubic hair staging (HR: 0.69 [95% CI: 0.44–1.07]; P = .10), compared with those with lower BLLs. Pubertal onset occurred 6 to 8 months later, on average, for boys with high BLLs, compared with those with BLLs of <5 μg/dL. CONCLUSION: Higher BLLs were associated with later pubertal onset in this prospective study of peripubertal Russian boys.

Predictors of Serum Dioxins and PCBs among Peripubertal Russian Boys

Background Although sources and routes of exposure to dioxins and polychlorinated biphenyls (PCBs) have been studied, information regarding exposure among children is limited. Breast-feeding 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.

Serum Concentrations of Organochlorine Pesticides and Growth among Russian Boys

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.

Dioxin Exposure and Age of Pubertal Onset among Russian Boys

Background: Animal data demonstrate associations of dioxin, furan, and polychlorinated biphenyl (PCB) exposures with altered male gonadal maturation. It is unclear whether these associations apply to human populations. Objectives: We investigated the association of dioxins, furans, PCBs, and corresponding toxic equivalent (TEQ) concentrations with pubertal onset among boys in a dioxin-contaminated region. Methods: Between 2003 and 2005, 499 boys 8–9 years of age were enrolled in a longitudinal study in Chapaevsk, Russia. Pubertal onset [stage 2 or higher for genitalia (G2+) or testicular volume (TV) > 3 mL] was assessed annually between ages 8 and 12 years. Serum levels at enrollment were analyzed by the Centers for Disease Control and Prevention, Atlanta, Georgia, USA. We used Cox proportional hazards models to assess age at pubertal onset as a function of exposure adjusted for potential confounders. We conducted sensitivity analyses excluding boys with pubertal onset at enrollment. Results: The median (range) total serum TEQ concentration was 21 (4–175) pg/g lipid, approximately three times higher than values in European children. At enrollment, boys were generally healthy and normal weight (mean body mass index, 15.9 kg/m2), with 30% having entered puberty by G2+ and 14% by TV criteria. Higher dioxin TEQs were associated with later pubertal onset by TV (hazard ratio = 0.68, 95% confidence interval, 0.49–0.95 for the highest compared with the lowest quartile). Similar associations were observed for 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin concentrations for TV but not G2+. Results were robust to sensitivity analyses. Conclusions: Findings support an association of higher peripubertal serum dioxin TEQs and concentrations with later male pubertal onset reflected in delayed testicular maturation.

Serum Dioxins and Polychlorinated Biphenyls Are Associated With Growth Among Russian Boys

OBJECTIVE: We evaluated the associations of serum dioxins and polychlorinated biphenyls (PCBs) with longitudinally assessed growth measurements among peripubertal Russian boys. METHODS: A total of 499 boys from Chapaevsk, Russia, aged 8 to 9 years were enrolled in the study from 2003 to 2005 and were followed prospectively for 3 years. Blood samples were collected and physical examinations were conducted at entry and repeated at annual study visits. Multivariate mixed-effects regression models for repeated measures were used to examine the associations of serum dioxins and PCBs with longitudinal measurements of BMI, height, and height velocity. RESULTS: Serum dioxin (total 2005 toxic equivalency [TEQ] median: 21.1 pg/g lipid) and PCBs (median sum of PCBs: 250 ng/g lipid) were measured in 468 boys. At study entry and during 3 years of follow-up, >50% of the boys had age-adjusted BMI and height z scores within 1 SD of World Health Organization–standardized mean values for age. Boys in the highest exposure quintile of the sum of dioxin and PCB concentrations and total TEQs had a significant decrease in mean BMI z scores of 0.67 for dioxins and TEQs and 1.04 for PCBs, compared with boys in the lowest exposure quintile. Comparison of the highest versus the lowest quintile revealed that higher serum PCB concentrations were associated with significantly lower height z scores (mean z-score decrease: 0.41) and height velocity (mean decrease: 0.19 cm/year) after 3 years of follow-up. CONCLUSIONS: Our findings suggest that exposures to dioxins and PCBs are associated with reduced growth during the peripubertal period and may compromise adult body mass, stature, and health.

Temporal trends in serum concentrations of polychlorinated dioxins, furans, and PCBs among adult women living in Chapaevsk, Russia: a longitudinal study from 2000 to 2009

BackgroundThe present study assessed the temporal trend in serum concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls (PCBs) among residents of a Russian town where levels of these chemicals are elevated due to prior industrial activity.MethodsTwo serum samples were collected from eight adult women (in 2000 and 2009), and analyzed with gas chromatography-high-resolution mass spectrometry.ResultsThe average total toxic equivalency (TEQ) decreased by 30% (from 36 to 25 pg/g lipid), and the average sum of PCB congeners decreased by 19% (from 291 to 211 ng/g lipid). Total TEQs decreased for seven of the eight women, and the sum of PCBs decreased for six of eight women. During this nine year period, larger decreases in serum TEQs and PCBs were found in women with greater increases in body mass index.ConclusionsThis study provides suggestive evidence that average serum concentrations of dioxins, furans, and PCBs are decreasing over time among residents of this town.

Predictors of serum chlorinated pesticide concentrations among prepubertal Russian boys

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—hexachlorobenzene (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. Citation: Lam T, Williams PL, Burns JS, Sergeyev O, Korrick SA, Lee MM, Birnbaum LS, Revich B, Altshul LM, Patterson DG Jr, Turner WE, Hauser R. 2013. Predictors of serum chlorinated pesticide concentrations among prepubertal Russian boys. Environ Health Perspect 121:1372–1377; http://dx.doi.org/10.1289/ehp.1306480

Blood Lead Levels and Serum Insulin-Like Growth Factor 1 Concentrations in Peripubertal Boys

Background: Childhood lead exposure has been associated with growth delay. However, the association between blood lead levels (BLLs) and insulin-like growth factor 1 (IGF-1) has not been characterized in a large cohort with low-level lead exposure. Methods: We recruited 394 boys 8–9 years of age from an industrial Russian town in 2003–2005 and followed them annually thereafter. We used linear regression models to estimate the association of baseline BLLs with serum IGF-1 concentration at two follow-up visits (ages 10–11 and 12–13 years), adjusting for demographic and socioeconomic covariates. Results: At study entry, median BLL was 3 μg/dL (range, < 0.5–31 μg/dL), most boys (86%) were prepubertal, and mean ± SD height and BMI z-scores were 0.14 ± 1.0 and –0.2 ± 1.3, respectively. After adjustment for covariates, the mean follow-up IGF-1 concentration was 29.2 ng/mL lower (95% CI: –43.8, –14.5) for boys with high versus low BLL (≥ 5 μg/dL or < 5 μg/dL); this difference persisted after further adjustment for pubertal status. The association of BLL with IGF-1 was stronger for mid-pubertal than prepubertal boys (p = 0.04). Relative to boys with BLLs < 2 μg/dL, adjusted mean IGF-1 concentrations decreased by 12.8 ng/mL (95% CI: –29.9, 4.4) for boys with BLLs of 3–4 μg/dL; 34.5 ng/mL (95% CI: –53.1, –16.0) for BLLs 5–9 μg/dL; and 60.4 ng/mL (95% CI: –90.9, –29.9) for BLLs ≥ 10 μg/dL. Conclusions: In peripubertal boys with low-level lead exposure, higher BLLs were associated with lower serum IGF-1. Inhibition of the hypothalamic–pituitary–growth axis may be one possible pathway by which lead exposure leads to growth delay.

A Longitudinal Study of Peripubertal Serum Organochlorine Concentrations and Semen Parameters in Young Men: The Russian Children's Study.

Background: Exposures to endocrine-disrupting chemicals during critical phases of testicular development may be related to poorer semen parameters. However, few studies have assessed the association between childhood organochlorine (OC) exposure and adult semen parameters. Objective: We examined whether peripubertal serum OC concentrations are associated with semen parameters among young Russian men. Methods: From 2003 through 2005, 516 boys were enrolled at age 8–9 years and followed for up to 10 years. Serum OCs were measured in the enrollment samples using high-resolution mass spectrometry. At 18–19 years, 133 young men provided 1 or 2 semen samples (256 samples) collected approximately 1 week apart, which were analyzed for volume, sperm concentration, and motility. Unadjusted and adjusted linear mixed models were used to examine the associations of quartiles of lipid-standardized concentrations of dioxins [2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated dibenzo-p-dioxins (PCDDs)], furans, polychlorinated biphenyls (PCBs), and corresponding toxic equivalents (TEQs) with semen parameters. Results: The median (range) for TCDD was 2.9 (0.4–12.1) pg/g lipid and PCDD TEQ was 8.7 (1.0–36.0) pg TEQ/g lipid. Higher quartiles of TCDD and PCDD TEQs were associated with lower sperm concentration, total sperm count, and total motile sperm count (p-trends ≤ 0.05). The highest quartile of peripubertal serum TCDD concentrations was associated with a decrease (95% CI) of 40% (18, 66%), 29% (3, 64%), and 30% (2, 70%) in sperm concentration, total sperm count, and total motile sperm count, respectively, compared with the lowest quartile. Similar associations were observed for serum PCDD TEQs with semen parameters. Serum PCBs, furans, and total TEQs were not associated with semen parameters. Conclusion: Higher peripubertal serum TCDD concentrations and PCDD TEQs were associated with poorer semen parameters. Citation: Mínguez-Alarcón L, Sergeyev O, Burns JS, Williams PL, Lee MM, Korrick SA, Smigulina L, Revich B, Hauser R. 2017. A longitudinal study of peripubertal serum organochlorine concentrations and semen parameters in young men: the Russian Children’s Study. Environ Health Perspect 125:460–466; http://dx.doi.org/10.1289/EHP25