Polybrominated Diphenyl Ether (PBDE) Flame Retardants and Thyroid Hormone during Pregnancy

Background

Human exposure to polybrominated diphenyl ether (PBDE) flame retardants has increased exponentially over the last three decades. Animal and human studies suggest that PBDEs may disrupt thyroid function. Although thyroid hormone (TH) of maternal origin plays an essential role in normal fetal brain development, there is a paucity of human data regarding associations between exposure to PBDEs and maternal TH levels during pregnancy.

Objectives

Our goal was to determine whether PBDE serum concentrations are associated with TH levels in pregnant women.

Methods

We measured the concentration of 10 PBDE congeners, free thyroxine (T₄), total T_4, and thyroid-stimulating hormone (TSH) in 270 pregnant women around the 27th week of gestation.

Results

Serum concentrations of individual PBDE congeners with detection frequencies > 50% (BDEs 28, 47, 99, 100, and 153) and their sum (∑PBDEs) were inversely associated with TSH levels. Decreases in TSH ranged between 10.9% [95% confidence interval (CI), −20.6 to 0.0] and 18.7% (95% CI, −29.2 to −4.5) for every 10-fold increase in the concentration of individual congeners. Odds of subclinical hyperthyroidism (low TSH but normal T₄) were also significantly elevated in participants in the highest quartile of ∑PBDEs and BDEs 100 and 153 relative to those in the first quartile. Associations between PBDEs and free and total T₄ were not statistically significant. Results were not substantially altered after the removal of outliers and were independent of the method used to adjust for blood lipid levels and to express ∑PBDEs.

Conclusions

Results suggest that exposure to PBDEs is associated with lower TSH during pregnancy. Findings may have implications for maternal health and fetal development.     

Maternal Polybrominated Diphenyl Ether (PBDE) Exposure and Thyroid Hormones in Maternal and Cord Sera: The HOME Study,Cincinnati, USA

Background

Polybrominated diphenyl ethers (PBDEs) reduce blood concentrations of thyroid hormones in laboratory animals, but it is unclear whether PBDEs disrupt thyroid hormones in pregnant women or newborn infants.

Objectives

We investigated the relationship between maternal PBDE levels and thyroid hormone concentrations in maternal and cord sera.

Methods

We used data from the Health Outcomes and Measures of the Environment (HOME)Study, a prospective birth cohort of 389 pregnant women in Cincinnati, Ohio, who were enrolled from 2003 through 2006 and delivered singleton infants. Maternal serum PBDE concentrations were measured at enrollment (16 ± 3 weeks of gestation). Thyroid hormone concentrations were measured in maternal serum at enrollment (n = 187) and in cord serum samples (n = 256).

Results

Median maternal serum concentrations of BDEs 28 and 47 were 1.0 and 19.1 ng/g lipid, respectively. A 10-fold increase in BDEs 28 and 47 concentrations was associated with a 0.85-μg/dL [95% confidence interval (CI): 0.05, 1.64] and 0.82-μg/dL (95% CI: 0.12, 1.51) increase in maternal total thyroxine concentrations (TT₄), respectively. Both congeners were also positively associated with maternal free thyroxine (FT₄). We also observed positive associations between BDE-47 and maternal total and free triiodothyronine (TT₃ and FT₃). A 10-fold increase in BDE-28 was associated with elevated FT₃ concentrations (β = 0.14 pg/mL; 95% CI: 0.02, 0.26). In contrast, maternal PBDE levels were not associated with thyroid hormone concentrations in cord serum.

Conclusions

These findings suggest that maternal PBDE exposure, particularly BDEs 28 and 47, are associated with maternal concentrations of T₄ and T₃ during pregnancy.

Citation

Vuong AM, Webster GM, Romano ME, Braun JM, Zoeller RT, Hoofnagle AN, Sjödin A, Yolton K, Lanphear BP, Chen A. 2015. Maternal polybrominated diphenyl ether (PBDE) exposure and thyroid hormones in maternal and cord sera: the HOME Study, Cincinnati, USA. Environ Health Perspect 123:1079–1085; http://dx.doi.org/10.1289/ehp.1408996     

Individual Characteristics Associated with PBDE Levels in U.S. Human Milk Samples

Background

Reported polybrominated diphenyl ether (PBDE) concentrations in human samples in the United States have been higher than in Europe and Asia. Little is known about factors that contribute to individual variability in body burden.

Objective

In this large study we measured PBDE concentrations in human milk from the United States during 2004–2006. We assessed characteristics associated with concentrations in milk and change in milk concentration between 3 and 12 months postpartum.

Methods

We analyzed 303 milk samples obtained 3 months postpartum for PBDEs. A second sample was analyzed for 83 women still lactating 12 months postpartum. PBDE concentrations in milk and variability by individual characteristics such as age, parity, and prepregnancy body mass index (BMI) were evaluated using generalized linear models.

Results

PBDE congeners BDEs 28, 47, 99, 100, and 153 were detected in > 70% of samples. BDE-47 concentrations were the highest, ranging from below the limit of detection to 1,430 ng/g lipid, with a median of 28 ng/g lipid. Concentrations of most individual PBDE congeners and the sum of BDEs 28, 47, 99, 100, and 153 (∑PBDE) were lower among mothers > 34 years of age compared with those 25–29 years of age and higher among mothers with high compared with normal BMI, after adjustment for other covariates. Parity was not associated with PBDE concentration. The change in ∑PBDE concentration in milk between 3 and 12 months postpartum was highly variable (median increase, 14%; interquartile range, −26% to 50%).

Conclusions

PBDEs were detected in nearly all human milk samples, varying by maternal weight and age and over the course of breast-feeding.     

In Utero and Childhood Polybrominated Diphenyl Ether Exposures and Body Mass at Age 7 Years: The CHAMACOS Study

Background

Polybrominated diphenyl ethers (PBDEs) are lipophilic flame retardants that bioaccumulate in humans. Child serum PBDE concentrations in California are among the highest worldwide. PBDEs may be associated with obesity by disrupting endocrine systems.

Objective

In this study, we examined whether pre- and postnatal exposure to the components of pentaBDE mixture was associated with childhood obesity in a population of Latino children participating in a longitudinal birth cohort study in the Salinas Valley, California.

Methods

We measured PBDEs in serum collected from 224 mothers during pregnancy and their children at 7 years of age, and examined associations with body mass index (BMI) at age 7 years.

Results

Maternal PBDE serum levels during pregnancy were associated with higher BMI z-scores in boys (BMI z-score β_adjusted = 0.26; 95% CI: –0.19, 0.72) but lower scores in girls (BMI z-score β_adjusted = –0.41; 95% CI: –0.87, –0.05) at 7 years of age (p_interaction = 0.04). In addition, child’s serum BDE-153 concentration (log₁₀), but not other pentaBDE congeners, demonstrated inverse associations with BMI at age 7 years (BMI z-score β_adjusted = –1.15; 95% CI: –1.53, –0.77), but there was no interaction by sex.

Conclusions

We estimated sex-specific associations with maternal PBDE levels during pregnancy and BMI at 7 years of age, finding positive associations in boys and negative associations in girls. Children’s serum BDE-153 concentrations were inversely associated with BMI at 7 years with no difference by sex. Future studies should examine the longitudinal trends in obesity with PBDE exposure and changes in hormonal environment as children transition through puberty, as well as evaluate the potential for reverse causality.

Citation

Erkin-Cakmak A, Harley KG, Chevrier J, Bradman A, Kogut K, Huen K, Eskenazi B. 2015. In utero and childhood polybrominated diphenyl ether exposures and body mass at age 7 years: the CHAMACOS Study. Environ Health Perspect 123:636–642; http://dx.doi.org/10.1289/ehp.1408417     

Polybrominated Diphenyl Ether Exposure and Thyroid Function Tests in North American Adults

Background:

Polybrominated diphenyl ethers (PBDEs) are flame-retardant chemicals that are added to many consumer products. Multiple animal studies have shown PBDEs to be thyroid hormone (TH) disruptors. Epidemiologic evidence of PBDE exposure associated with TH disruption has been inconclusive.

Objectives:

We used repeated measures to estimate associations between serum PBDE concentrations and THs in a North American adult cohort.

Methods:

From 2010 to 2011, we collected ≤ 3 serum samples at approximately 6-month intervals from 52 healthy adult office workers from Boston, Massachusetts, for analysis of PBDE congeners and THs.

Results:

The geometric mean sum concentrations of the most prevalent PBDE congeners (BDE-28, BDE-47, BDE-99, BDE-100, and BDE-153) were 22 ng/g lipid in winter 2010, 23 ng/g lipid in summer 2010, and 19 ng/g lipid in winter 2011. BDE-47 was the predominant congener. Based on a multivariable mixed regression model, we estimated that on average, a 1-ng/g serum increase in BDE-47 was associated with a 2.6-μg/dL decrease in total thyroxine (T4) (95% CI: –4.7, –0.35). Total T4 was inversely associated with each PBDE congener. Serum concentrations of PBDEs were not strongly associated with total triiodothyronine (T3), free T4, or thyroid-stimulating hormone (TSH).

Conclusion:

These results are consistent with those from animal studies showing that exposure to PBDEs is associated with a decrease in serum T4. Because the other TH concentrations did not appear to be associated with BDE exposures, our findings do not indicate effects on the pituitary–thyroid axis. Taken together, our findings suggest that PBDE exposure might decrease the binding of T4 to serum T4 binding proteins.

Citation:

Makey CM, McClean MD, Braverman LE, Pearce EN, He XM, Sjödin A, Weinberg JM, Webster TF. 2016. Polybrominated diphenyl ether exposure and thyroid function tests in North American adults. Environ Health Perspect 124:420–425; http://dx.doi.org/10.1289/ehp.1509755     

Serum Polybrominated Diphenyl Ether (PBDE) Levels Are Higher in Children (2–5 Years of Age) than in Infants and Adults

Background

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in many products and have been detected in human samples worldwide. Limited data show that concentrations are elevated in young children.

Objectives

We investigated the association between PBDEs and age with an emphasis on young children from Australia in 2006–2007.

Methods

We collected human blood serum samples (n = 2,420), which we stratified by age and sex and pooled for analysis of PBDEs.

Results

The sum of BDE-47, -99, -100, and -153 concentrations (∑₄PBDE) increased from 0–0.5 years (mean ± SD, 14 ± 3.4 ng/g lipid) to peak at 2.6–3 years (51 ± 36 ng/g lipid; p < 0.001) and then decreased until 31–45 years (9.9 ± 1.6 ng/g lipid). We observed no further significant decrease among ages 31–45, 45–60 (p = 0.964), or > 60 years (p = 0.894). The mean ∑₄PBDE concentration in cord blood (24 ± 14 ng/g lipid) did not differ significantly from that in adult serum at ages 15–30 (p = 0.198) or 31–45 years (p = 0.140). We found no temporal trend when we compared the present results with Australian PBDE data from 2002–2005. PBDE concentrations were higher in males than in females; however, this difference reached statistical significance only for BDE-153 (p = 0.05).

Conclusions

The observed peak concentration at 2.6–3 years of age is later than the period when breast-feeding is typically ceased. This suggests that in addition to the exposure via human milk, young children have higher exposure to these chemicals and/or a lower capacity to eliminate them.     

Insights into PBDE Uptake,Body Burden,and Elimination Gained from Australian Age–Concentration Trends Observed Shortly after Peak Exposure

Background

Population pharmacokinetic models combined with multiple sets of age–concentration biomonitoring data facilitate back-calculation of chemical uptake rates from biomonitoring data.

Objectives

We back-calculated uptake rates of PBDEs for the Australian population from multiple biomonitoring surveys (top-down) and compared them with uptake rates calculated from dietary intake estimates of PBDEs and PBDE concentrations in dust (bottom-up).

Methods

Using three sets of PBDE elimination half-lives, we applied a population pharmacokinetic model to the PBDE biomonitoring data measured between 2002–2003 and 2010–2011 to derive the top-down uptake rates of four key PBDE congeners and six age groups. For the bottom-up approach, we used PBDE concentrations measured around 2005.

Results

Top-down uptake rates of Σ₄BDE (the sum of BDEs 47, 99, 100, and 153) varied from 7.9 to 19 ng/kg/day for toddlers and from 1.2 to 3.0 ng/kg/day for adults; in most cases, they were—for all age groups—higher than the bottom-up uptake rates. The discrepancy was largest for toddlers with factors up to 7–15 depending on the congener. Despite different elimination half-lives of the four congeners, the age–concentration trends showed no increase in concentration with age and were similar for all congeners.

Conclusions

In the bottom-up approach, PBDE uptake is underestimated; currently known pathways are not sufficient to explain measured PBDE concentrations, especially in young children. Although PBDE exposure of toddlers has declined in the past years, pre- and postnatal exposure to PBDEs has remained almost constant because the mothers’ PBDE body burden has not yet decreased substantially.

Citation

Gyalpo T, Toms LM, Mueller JF, Harden FA, Scheringer M, Hungerbühler K. 2015. Insights into PBDE uptake, body burden, and elimination gained from Australian age–concentration trends observed shortly after peak exposure. Environ Health Perspect 123:978–984; http://dx.doi.org/10.1289/ehp.1408960     

Diet Contributes Significantly to the Body Burden of PBDEs in the General U.S. Population

Background

Exposure of the U.S. population to polybrominated diphenyl ethers (PBDEs) is thought to be via exposure to dust and diet. However, little work has been done to empirically link body burdens of these compounds to either route of exposure.

Objectives

The primary goal of this research was to evaluate the dietary contribution to PBDE body burdens in the United States by linking serum levels to food intake.

Methods

We used two dietary instruments—a 24-hr food recall (24FR) and a 1-year food frequency questionnaire (FFQ)—to examine food intake among participants of the 2003–2004 National Health and Nutrition Examination Survey. We regressed serum concentrations of five PBDEs (BDE congeners 28, 47, 99, 100, and 153) and their sum (∑PBDE) against diet variables while adjusting for age, sex, race/ethnicity, income, and body mass index.

Results

∑PBDE serum concentrations among vegetarians were 23% (p = 0.006) and 27% (p = 0.009) lower than among omnivores for 24FR and 1-year FFQ, respectively. Serum levels of five PBDE congeners were associated with consumption of poultry fat: Low, medium, and high intake corresponded to geometric mean ∑PBDE concentrations of 40.6, 41.9, and 48.3 ng/g lipid, respectively (p = 0.0005). We observed similar trends for red meat fat, which were statistically significant for BDE-100 and BDE-153. No association was observed between serum PBDEs and consumption of dairy or fish. Results were similar for both dietary instruments but were more robust using 24FR.

Conclusions

Intake of contaminated poultry and red meat contributes significantly to PBDE body burdens in the United States.     

Correlation of body mass index levels with menarche in adolescent girls in Shaanxi,China: a cross sectional study

Background

Menarche is a milestone for adolescent girls. The timing of menarche is influenced by genetics, social status and nutritional status (e.g., height, weight and body mass index [BMI]) and impacts future health (e.g., obesity and breast cancer). There have been many studies on trends in age at menarche among adolescent girls in China, but few have investigated associations between growth status and the timing of menarche. This study examined the association between age at menarche and growth status among adolescent girls in Western China.

Methods

The participants in this cross sectional study came from three geographical regions of Shaanxi Province. A total of 533 adolescent girls from urban and rural areas were randomly selected. Trained investigators administered a standard questionnaire to each participant during a face-to-face interview and carried out anthropometric measurements.

Results

The average age at menarche was 13.3 years. There were statistically significant differences in BMI z-scores between pre-menarcheal and post-menarcheal girls of the same age and these differences were related to socioeconomic factors. Girls who had reached menarche, in particular those aged 13–14 years, were significantly taller (P?<?0.01) and had higher BMI (P?<?0.01) than girls in the same age group who had not reached menarche.

Conclusions

BMI is associated with the timing of menarche but socioeconomic factors are also important.

     

Brominated Flame Retardants and Other Persistent Organohalogenated Compounds in Relation to Timing of Puberty in a Longitudinal Study of Girls

Background

Exposure to hormonally active chemicals could plausibly affect pubertal timing, so we are investigating this in the Breast Cancer and the Environment Research Program.

Objectives

Our goal was to examine persistent organic pollutants (POPs) in relation to pubertal onset.

Methods

Ethnically diverse cohorts of 6- to 8-year-old girls (n = 645) provided serum for measure of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and lipids. Tanner stages [breast (B) and pubic hair (PH)], and body mass index (BMI) were measured at up to seven annual clinic visits. Using accelerated failure time models, we calculated time ratios (TRs) for age at Tanner stages 2 or higher (2+) and POPs quartiles (Q1–4), adjusting for confounders (race/ethnicity, site, caregiver education, and income). We also calculated prevalence ratios (PRs) of Tanner stages 2+ at time of blood sampling.

Results

Cross-sectionally, the prevalence of B2+ and PH2+ was inversely related to chemical serum concentrations; but after adjustment for confounders, only the associations with B2+, not PH2+, were statistically significant. Longitudinally, the age at pubertal transition was consistently older with greater chemical concentrations; for example: adjusted TR for B2+ and Q4 for ΣPBDE = 1.05; 95% CI: 1.02, 1.08, for ΣPCB = 1.05; 95% CI: 1.01, 1.08, and for ΣOCP = 1.10; 95% CI: 1.06, 1.14, indicating median ages of about 6 and 11 months older than least exposed, and with similar effect estimates for PH2+. Adjusting for BMI attenuated associations for PCBs and OCPs but not for PBDEs.

Conclusions

This first longitudinal study of puberty in girls with serum POPs measurements (to our knowledge) reveals a delay in onset with higher concentrations.

Citation

Windham GC, Pinney SM, Voss RW, SjÖdin A, Biro FM, Greenspan LC, Stewart S, Hiatt RA, Kushi LH. 2015. Brominated flame retardants and other persistent organohalogenated compounds in relation to timing of puberty in a longitudinal study of girls. Environ Health Perspect 123:1046–1052; http://dx.doi.org/10.1289/ehp.1408778     

Contamination of U.S. butter with polybrominated diphenyl ethers from wrapping paper

Objectives

Our aim was to report the first known incidence of U.S. butter contamination with extremely high levels of polybrominated diphenyl ethers (PBDEs).

Methods

Ten butter samples were individually analyzed for PBDEs. One of the samples and its paper wrapper contained very high levels of higher-brominated PBDEs. Dietary estimates were calculated using the 2007 U.S. Department of Agriculture Loss-Adjusted Food Availability data, excluding the elevated sample.

Results

The highly contaminated butter sample had a total upper bound PBDE level of 42,252 pg/g wet weight (ww). Levels of brominated diphenyl ether (BDE)-206, -207, and -209 were 2,000, 2,290, and 37,600 pg/g ww, respectively. Its wrapping paper contained a total upper-bound PBDE concentration of 804,751 pg/g ww, with levels of BDE-206, -207, and -209 of 51,000, 11,700, and 614,000 pg/g, respectively. Total PBDE levels in the remaining nine butter samples ranged from 180 to 1,212 pg/g, with geometric mean of 483 and median of 284 pg/g. Excluding the outlier, total PBDE daily intake from all food was 22,764 pg/day, lower than some previous U.S. dietary intake estimates.

Conclusion

Higher-brominated PBDE congeners were likely transferred from contaminated wrapping paper to butter. A larger representative survey may help determine how frequently PBDE contamination occurs. Sampling at various stages in food production may identify contamination sources and reduce risk.     

Longitudinal influences of friends and parents upon unprotected vaginal intercourse in adolescents

Background

Both friends and parents may influence occurrence of adolescent sexual intercourse, but these influences have not been studied together and prospectively.

Study Design

We conducted a longitudinal analysis of a nationally representative sample of adolescents aged 15–18 years (n=6649), the National Longitudinal Study of Adolescent Health (Add Health). Baseline in-home and school interviews were conducted during 1995 and follow-up interviews in 1996. The main outcome measure was self-reported unprotected vaginal intercourse.

Results

In models which adjusted for age, race, parental attitudes towards contraception and pregnancy, and adolescent sexual intercourse practices at baseline, having a friend who engaged in sexual intercourse at baseline, either unprotected (OR 2.2, 95% CI 1.6–3.2) or protected (OR 1.8, 95% CI 1.4–2.4), increased the odds of unprotected intercourse vs. never intercourse in the adolescent at follow-up (p<.001). A distant relationship with the father (OR 2.4, 95% CI 1.3–4.3) vs. a close relationship at baseline also increased the odds of unprotected intercourse at follow-up compared to never intercourse (p=.028). Parental attitudes were not associated with the outcome after consideration of the adolescent's attitudes and baseline sexual practices.

Conclusions

Having a friend who engages in sexual intercourse, unprotected or protected, increases the risk of unprotected intercourse. Parental attitudes are less influential after consideration of adolescent baseline attitudes and sexual practices, suggesting that parental influences are strongest before 15 years of age. Our results suggest that early intervention among both parents and adolescents may decrease the risk of unprotected intercourse.     

Menstrual effects among women exposed to polychlorinated biphenyls and dibenzofurans

Background

Polychlorinated biphenyls (PCBs), dibenzofurans (PCDFs), and dibenzo-dioxins (PCDDs) may affect the female reproductive system in humans. A mass poisoning occurred in Taiwan due to PCBs/PCDFs-contaminated cooking oil, and was called the Yucheng (oil-disease in Chinese). We aimed to determine whether Yucheng women were affected in their menstruation.

Methods

After the event, we followed the exposed individuals and an age-matched neighborhood reference group. Menstrual cycle characteristics and age at menarche were obtained by a telephone interview. We used multiple linear and logistic regression to examine the association between PCBs/PCDFs and menstrual cycle characteristics, after adjusting for confounding factors.

Results

Totally 445 women responded satisfactorily and were included in the analyses of menstrual characteristics. Menstrual cycle irregularity and dysmenorrheal did not differ between Yucheng and referents. Yucheng women's menstrual cycles were 0.5 (95% CI: 0.0–0.5; p=0.03) days shorter than those of the referents. The Yucheng women with skin lesions caused by PCBs/PCDFs were more prominently affected, with the cycles 1.2 days shorter than the referents. Yucheng women exposed to PCBs/PCDFs at the premenacheal period had reduced cycle length (−0.7 day, 95% CI: −1.4 to 0.0; p=0.04) and longer days of menstrual flow (0.5 day, 95% CI: 0.0–1.0; p=0.04). Among those women who were exposed at an age of 5–9 years, menarche started slightly earlier with borderline significance.

Conclusions

Shorter menstrual cycle length and a longer duration of bleeding in each cycle were found among women previously exposed to PCBs/PCDFs. These effects were more obviously observed among those exposed at premenarcheal ages.     

Impact of age on the association between body mass index and all-cause mortality in patients with atrial fibrillation

Objectives

To explore the impact of age on the association between body mass index (BMI) and all-cause mortality in patients with atrial fibrillation (AF).

Methods

A total of 1991 patients with AF (69 ± 13 years, 54.9% female) were divided into three age groups: < 65 years, 65-75 years, and > 75 years, and followed for one year. The primary outcome was defined as all-cause mortality, with secondary outcomes including thromboembolism and major bleeding. Cox regression models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

Compared to patients aged < 65 years, elder groups had much lower BMI and more comorbidities other than a lower prevalence of valvular heart disease. During one-year follow-up, 277 (13.9%) patients died, 158 (7.9%) underwent thromboembolism events and 26 (1.3%) had major bleeding. Mortality and thromboembolism risk were both notably higher in patients with advanced age (all P values < 0.001). Using normal weight patients as reference, mortality risk was significantly lower in overweight (HR 0.548; 95% CI 0.404-0.744) and obese patients (HR 0.536; 95% CI 0.325-0.883) for the entire cohort, with reduced death risk mainly observed in overweight patients aged 65-75 years (HR 0.285; 95% CI 0.131-0.621) and aged > 75 years (HR 0.686; 95% CI 0.473-0.993), but not in patients aged < 65 years. Continuous analyses of BMI indicated consistent results.

Conclusion

High BMI is associated with reduced mortality rate in patients with AF, and this association is affected by age, with the so-called “obesity paradox” confined to those with advanced age rather than young patients.

     

Why do studies show different associations between intrauterine exposure to maternal smoking and age at menarche?

Purpose

Studies suggests that intrauterine exposure to maternal smoking both accelerates or delays age at menarche. We hypothesize that these opposing findings relate to different infant and childhood growth patterns across cohorts.

Birth delivery mode modifies the associations between prenatal polychlorinated biphenyl (PCB) and polybrominated diphenyl ether (PBDE) and neonatal thyroid hormone levels

Background

Developing infants may be especially sensitive to hormone disruption from chemicals including polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs).

Objective

We investigated relationships between cord serum levels of PCBs and PBDEs and thyroid hormones measured in cord blood serum and neonatal blood spots.

Methods

We measured PCBs and PBDEs, thyrotropin (TSH), thyroxine (T₄) and free T₄ (FT₄) in cord blood serum from 297 infants who were delivered at the Johns Hopkins Hospital in 2004–2005. We abstracted results of total T₄ (TT₄) measured in blood spots collected in the hospital and at neonatal visits. We used delivery mode (augmented vaginal deliveries and nonelective cesarean deliveries) as a surrogate for intrapartum stress, which is known to alter cord blood thyroid hormones.

Results

In the full study population, no compounds were associated with a change in average TSH, FT₄, or TT₄. BDE-100 was associated with increased odds of low cord TT₄, BDE-153 with increased odds of low cord TT₄ and FT₄, and no compounds were associated with increased odds of high TSH. For infants born by spontaneous, vaginal, unassisted deliveries, PCBs were associated with lower cord TT₄ and FT₄ and lower TT₄ measured in neonatal blood spots. PBDEs showed consistent but mainly nonsignificant negative associations with TT₄ and FT₄ measurements.

Conclusions

Prenatal PCB and PBDE exposures were associated with reduced TT₄ and FT₄ levels among infants born by spontaneous, unassisted vaginal delivery. Intrapartum stress associated with delivery mode may mask hormonal effects of PCBs and PBDEs.     

Association Between Insulin-Like Growth Factor-1 and Frailty Among Older Adults

Objectives

Frailty is a course experienced in advanced aging. Identification of a biological factor associated with frailty is required. Although serum insulin-like growth factor-1 (IGF-1) is a potential factor related with frailty, consensus has not been reached regarding this relationship. This study aimed to investigate the association between IGF-1 and frailty in older adults.

Design

Cross-sectional study.

Setting

Cohort study that was part of the “National Center for Geriatrics and Gerontology–Study of Geriatric Syndromes.”

Participants

The study participants were 4133 older adults (mean age, 71.8 ± 5.4 years).

Measurements

We assessed serum IGF-1 levels and frailty status and collected demographic variables, including cognitive function, as covariates.

Results

Frailty and pre-frailty were present in 274 subjects (7%) and 1930 subjects (47%), respectively. Subjects were divided into four groups based on quartiles of IGF-1 levels. Multinomial logistic analysis showed that the lowest group had significant odds of pre-frailty (crude model: odds ratio [OR] 1.58, 95% confidence interval [CI] 1.30–1.90, p <.001; adjusted model: OR 1.38, 95% CI 1.13–1.68, p =.002) and frailty (crude model: OR 3.42, 95% CI 2.38-4.92, p <.001; adjusted model: OR 1.54, 95% CI 1.02–2.32, p =.039), compared with the highest group.

Conclusion

Lower serum IGF-1 levels were independently related with frailty in older adults.

     

Hydroxylated Metabolites of Polybrominated Diphenyl Ethers in Human Blood Samples from the United States

Background

A previous study from our laboratory showed that polybrominated diphenyl ethers (PBDEs) were metabolized to hydroxylated PBDEs (HO-PBDEs) in mice and that para-HO-PBDEs were the most abundant and, potentially, the most toxic metabolites.

Objective

The goal of this study was to determine the concentrations of HO-PBDEs in blood from pregnant women, who had not been intentionally or occupationally exposed to these flame retardants, and from their newborn babies.

Methods

Twenty human blood samples were obtained from a hospital in Indianapolis, Indiana, and analyzed for both PBDEs and HO-PBDEs using electron-capture negative-ionization gas chromatographic mass spectrometry.

Results

The metabolite pattern of HO-PBDEs in human blood was quite different from that found in mice; 5-HO-BDE-47 and 6-HO-BDE-47 were the most abundant metabolites of BDE-47, and 5′-HO-BDE-99 and 6′-HO-BDE-99 were the most abundant metabolites of BDE-99. The relative concentrations between precursor and corresponding metabolites indicated that BDE-99 was more likely to be metabolized than BDE-47 and BDE-100. In addition, three bromophenols were also detected as products of the cleavage of the diphenyl ether bond. The ratio of total hydroxylated metabolites relative to their PBDE precursors ranged from 0.10 to 2.8, indicating that hydroxylated metabolites of PBDEs were accumulated in human blood.

Conclusions

The quite different PBDE metabolite pattern observed in humans versus mice indicates that different enzymes might be involved in the metabolic process. Although the levels of HO-PBDE metabolites found in human blood were low, these metabolites seemed to be accumulating.