Pre- and postnatal polychlorinated biphenyl exposure and cognitive and behavioral development at age 45 Months in a cohort of Slovak children.

Evidence of associations of pre- and postnatal exposure to polychlorinated biphenyls (PCBs) with cognitive development beyond early childhood is inconsistent. A previous report from this cohort observed adverse associations between early life PCB exposures and infant Bayley scores at age 16 months. The present study examines pre- and postnatal PCB exposures in relation to both behavior and cognitive development at age 45 months. Participants were 472 mother-child pairs residing in an area of eastern Slovakia characterized by environmental contamination with PCBs, which resulted in elevated blood serum concentrations. PCB-153 and PCB-118 concentrations were measured in maternal and in infant 6-, 16-, and 45-month serum samples. At age 45 months, children were administered five subtests of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), and mothers completed the Child Behavior Checklist (CBCL). Negative binomial and multiple linear regressions were used to estimate PCB-CBCL and PCB-WPPSI-III subtest score associations, respectively. Pre- and postnatal levels of PCB-153 and PCB-118 were not associated with cognitive performance on the WPPSI-III in this cohort. There was some suggestion that higher postnatal PCB concentrations were associated with more sleep problems and feelings of depression and anxiousness.

A cohort study of developmental polychlorinated biphenyl (PCB) exposure in relation to post-vaccination antibody response at 6-months of age.

BACKGROUND: Extensive experimental data in animals indicate that exposure to polychlorinated biphenyls (PCBs) during pregnancy leads to changes in offspring immune function during the postnatal period. Whether developmental PCB exposure influences immunologic development in humans has received little study. METHODS: The study population was 384 mother-infant pairs recruited from two districts of eastern Slovakia for whom prospectively collected maternal, cord, and 6-month infant blood specimens were available. Several PCB congeners were measured in maternal, cord, and 6-month infant sera by high-resolution gas chromatography with electron capture detection. Concentrations of IgG-specific anti-haemophilus influenzae type b, tetanus toxoid, and diphtheria toxoid were assayed in 6-month infant sera using ELISA methods. Multiple linear regression was used to estimate the relation between maternal, cord, and 6-month infant PCB concentrations and the antibody concentrations evaluated at 6-months of age. RESULTS: Overall, there was little evidence of an association between infant antibody concentrations and PCB measures during the pre- and early postnatal period. In addition, our results did not show specificity in terms of associations limited to a particular developmental period (e.g. pre- vs. postnatal), a particular antibody, or a particular PCB congener. CONCLUSIONS: At the PCB concentrations measured in this cohort, which are high relative to most human populations today, we did not detect an association between maternal or early postnatal PCB exposure and specific antibody responses at 6-months of age.

Prenatal polychlorinated biphenyl exposures in eastern Slovakia modify effects of social factors on birthweight.

Polychlorinated biphenyls (PCB) were widely used for industrial purposes and consumer products, but because of their toxicity, production was banned by most industrialised countries in the late 1970s. In eastern Slovakia, they were produced until 1985. During 2002-04, a birth cohort of mothers (n = 1057) residing in two Slovak districts was enrolled at delivery, and their specimens and information were collected after birth. Congeners of PCBs were measured in maternal serum by high-resolution gas chromatography with electron capture detection. In this study, we used multiple linear regression to examine the effects of prenatal PCB exposure on birthweight adjusted for gestational age, controlling for inter-pregnancy interval, and maternal smoking, age, education, ethnicity, pre-pregnancy body mass index and height. The association between total maternal serum PCB levels and birthweight was not statistically significant. However, an interaction model indicated that maternal PCB concentrations were associated with lower birthweight in Romani boys. Based on the fitted regression model, the predicted birthweight of Romani boys at the 90th percentile of maternal PCBs (12.8 ng/mL) was 133 g lower than the predicted birthweight at the 10th percentile of maternal PCBs (1.6 ng/mL). This is a similar magnitude of effect to that observed for maternal smoking and birthweight. These results suggest that higher levels of PCBs in maternal blood sera may inhibit growth in boys, particularly in those already affected by social factors related to ethnicity. This study is consistent with previous findings that boys are more susceptible than girls to growth restriction induced by in utero organochlorine exposures, and further indicates that high PCBs may magnify the influence of social disadvantage in this vulnerable group of boys.

The effect of area HMO market share on cancer screening.

OBJECTIVE: Managed care may have widespread impacts on health care delivery for all patients in the areas where they operate. We examine the relationship between area managed care activity and screening for breast, cervical, and prostate cancer among patients enrolled in more managed care plans and patients who are enrolled in less managed plans. DATA AND METHODS: Data on cancer screening from the 1996 Medical Expenditure Panel Survey (MEPS) were linked to data on health maintenance organization (HMO) and preferred provider organization (PPO) market share and HMO competition at the metropolitan statistical area (MSA) level. Logistic regression analysis was used to examine the relationship between area managed care prevalence and the use of mammography, clinical breast examination, Pap smear, and prostate cancer screening in the past two years, controlling for important covariates. RESULTS: Among all patients, increases in area-level HMO market share are associated with increases in the appropriate use of mammography, clinical breast exam, and Pap smear (OR for high relative to low managed care areas are 1.75, p < .01, for mammography, 1.58, p < .05, for clinical breast exam, and 1.71, p < .01, for Pap smear). In analyses of subgroups, the relationship is significant only for individuals who are enrolled in the nonmanaged plans; there is no relationship for individuals in more managed plans. No relationship is observed between area HMO market share and prostate cancer screening in any analysis. Neither the level of competition between area HMOs nor area PPO market share is associated with screening rates. CONCLUSIONS: Area-level managed care activity can influence preventive care treatment patterns.

Prenatal and postnatal serum PCB concentrations and cochlear function in children at 45 months of age.

BACKGROUND: Some experimental and human data suggest that exposure to polychlorinated biphenyls (PCBs) may induce ototoxicity, though results of previous epidemiologic studies are mixed and generally focus on either prenatal or postnatal PCB concentrations exclusively. OBJECTIVES: Our aim was to evaluate the association between pre- and postnatal PCB concentrations in relation to cochlear status, assessed by distortion product otoacoustic emissions (DPOAEs), and to further clarify the critical periods in development where cochlear status may be most susceptible to PCBs. METHODS: A total of 351 children from a birth cohort in eastern Slovakia underwent otoacoustic testing at 45 months of age. Maternal pregnancy, cord, and child 6-, 16-, and 45-month blood samples were collected and analyzed for PCB concentrations. At 45 months of age, DPOAEs were assessed at 11 frequencies in both ears. Multivariate, generalized linear models were used to estimate the associations between PCB concentrations at different ages and DPOAEs, adjusting for potential confounders. RESULTS: Maternal and cord PCB-153 concentrations were not associated with DPOAEs at 45 months. Higher postnatal PCB concentrations at 6-, 16-, and 45-months of age were associated with lower (poorer) DPOAE amplitudes. When all postnatal PCB exposures were considered as an area-under-the-curve metric, an increase in PCB-153 concentration from the 25th to the 75th percentile was associated with a 1.6-dB SPL (sound pressure level) decrease in DPOAE amplitude (95% CI: -2.6, -0.5; p = 0.003). CONCLUSIONS: In this study, postnatal rather than maternal or cord PCB concentrations were associated with poorer performance on otoacoustic tests at age 45 months.

Toxicokinetic modeling of persistent organic pollutant levels in blood from birth to 45 months of age in longitudinal birth cohort studies.

BACKGROUND: Despite experimental evidence that lactational exposure to persistent organic pollutants (POPs) can impact health, results from epidemiologic studies are inconclusive. Inconsistency across studies may reflect the inability of current methods to estimate children's blood levels during specific periods of susceptibility. OBJECTIVES: We developed a toxicokinetic model to simulate blood POP levels in children from two longitudinal birth cohorts and aimed to validate it against blood levels measured at 6, 16, and 45 months of age. METHODS: The model consisted of a maternal and a child lipid compartment connected through placental diffusion and breastfeeding. Simulations were carried out based on individual physiologic parameters; duration of breastfeeding; and levels of POPs measured in maternal blood at delivery, cord blood, or breast milk. Model validity was assessed through regression analyses of simulated against measured blood levels. RESULTS: Simulated levels explained between 10% and 83% of measured blood levels depending on the cohort, the compound, the sample used to simulate children's blood levels, and child's age when blood levels were measured. Model accuracy was highest for estimated blood POP levels at 6 months based on maternal or cord blood levels. However, loss in model precision between the 6th and the 45th month was small for most compounds. CONCLUSIONS: Our validated toxicokinetic model can be used to estimate children's blood POP levels in early to mid-childhood. Estimates can be used in epidemiologic studies to evaluate the impact of exposure during hypothesized postnatal periods of susceptibility on health.

Pre- and postnatal polychlorinated biphenyl concentrations and longitudinal measures of thymus volume in infants.

BACKGROUND: Previously, we reported an association between higher maternal polychlorinated biphenyl (PCB) concentrations and smaller thymus volume in newborns in a birth cohort residing in eastern Slovakia. OBJECTIVE: In the present report we address whether thymus volume at later ages is influenced by prenatal and early postnatal PCB exposure. METHODS: At the time of delivery, 1,134 mother-infant pairs were enrolled. Maternal and 6- and 16-month infant blood samples were collected and analyzed for 15 PCB congeners. Thymus volume was measured in infants shortly after birth and at ages 6 and 16 months using ultrasonography. RESULTS: Higher maternal PCB concentration was associated with reduced thymus volume at birth [a 0.21 SD reduction in thymus volume for an increase in total maternal PCB concentration from the 10th to the 90th percentile; 95% confidence interval (CI): -0.37, -0.05], whereas maternal PCB concentration was not predictive of 6- and 16-month thymus volume. Six-month infant PCB concentration was associated with a 0.40 SD decrease in 6-month thymus volume (95% CI: -0.76, -0.04). There was also some suggestion that thymus volume at 16 months was positively associated with concurrent infant PCB concentration. CONCLUSIONS: The potential adverse effects of in utero PCB exposure on thymic development may extend beyond the neonatal period. Results from this highly exposed cohort provide suggestive evidence that postnatal PCB concentrations may be influential, but a smaller set of 6-month PCB measurements limited statistical power at that time point. Implications regarding impaired immunologic maturation or long-term clinical implications remain to be determined.

Analysis of the toxicogenomic effects of exposure to persistent organic pollutants (POPs) in Slovakian girls: correlations between gene expression and disease risk.

The chemical composition of persistent organic pollutants (POPs) in the environment is not uniform throughout the world, and these contaminants contain many structurally different lipophilic compounds. In a well-defined study cohort in the Slovak Republic, the POP chemicals present in the peripheral blood of exposed children were chemically analyzed. The chemical analysis data revealed that the relative concentration and profile of structurally different organic pollutants, including polychlorinated biphenyls (PCBs), 2,2'-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE), 2,2'-bis(4-chlorophenyl)-1,1,1-trichloro-ethane (p,p'-DDT), hexachlorobenzene (HCB) and ß-hexachlorocyclohexane (ß-HCH), may vary from individual to individual, even within the same exposure area. These chemicals can be broadly classified into two groups. The first group, the PCB congeners, primarily originated from industrial compounds and their byproducts. The second group of compounds originated from or was commonly used in the agricultural sector (e.g., DDT, HCB). The objective of this study was to examine the effects of the two POP exposure profiles on gene expression. For the study population, we selected pre-pubertal girls (mean age of 46.2±1.4 months) with high POP concentrations in their blood (>75% tile of total POP) and classified them in the high 'PCB' group when the total PCB concentration was significantly higher than the total concentration of other POP components and in the 'Other Than PCB' (OTP) group, when the total PCB concentration was significantly lower than the concentration of the other major POP constituents. A matched control group of girls (<25% tile of total POP) was selected for comparison purpose (n=5 per group). Our aims were to determine whether there were any common effects of high POP exposure at a toxicogenomic level and to investigate how exposure may affect physiological functions of the children in two different exposure scenarios. Global gene expression analysis using a microarray (Affymetrix Gene Chip Human genome U133 Plus 2.0 Array) platform was conducted on the total RNA of peripheral blood mononuclear cells from the girls. The results were analyzed by Partek GS, Louis, MI, which identified twelve genes (ATAD2B, BIVM, CD96, CXorf39, CYTH1 ETNK1, FAM13A, HIRA, INO80B, ODG1, RAD23B, and TSGA14) and two unidentified probe sets, as regulated differentially in both the PCB and OTP groups against the control group. The qRT-PCR method was used to validate the microarray results. The Ingenuity Pathway Analysis (IPA) software package identified the possible molecular impairments and disease risks associated with each gene set. Connective tissue disorders, genetic disorders, skeletal muscular disorders and neurological diseases were associated with the 12 common genes. The data therefore identified the potential molecular effects of POP exposure on a genomic level. This report underscores the importance of further study to validate the results in a random population and to evaluate the use of the identified genes as biomarkers for POP exposure.

Differential gene expression and a functional analysis of PCB-exposed children: understanding disease and disorder development.

The goal of the present study is to understand the probable molecular mechanism of toxicities and the associated pathways related to observed pathophysiology in high PCB-exposed populations. We have performed a microarray-based differential gene expression analysis of children (mean age 46.1 months) of Central European descent from Slovak Republic in a well-defined study cohort. The subset of children having high blood PCB concentrations (>75 percentile) were compared against their low PCB counterparts (<25 percentile), with mean lipid-adjusted PCB values of 3.02±1.3 and 0.06±0.03 ng/mg of serum lipid, for the two groups, respectively (18.1±4.4 and 0.3±0.1 ng/ml of serum). The microarray was conducted with the total RNA from the peripheral blood mononuclear cells of the children using an Affymetrix platform (GeneChip Human genome U133 Plus 2.0 Array) and was analyzed by Gene Spring (GX 10.0). A highly significant set of 162 differentially expressed genes between high and low PCB groups (p value <0.00001) were identified and subsequently analyzed using the Ingenuity Pathway Analysis tool. The results indicate that Cell-To-Cell Signaling and Interaction, Cellular Movement, Cell Signaling, Molecular Transport, and Vitamin and Mineral Metabolism were the major molecular and cellular functions associated with the differentially altered gene set in high PCB-exposed children. The differential gene expressions appeared to play a pivotal role in the development of probable diseases and disorders, including cardiovascular disease and cancer, in the PCB-exposed population. The analyses also pointed out possible organ-specific effects, e.g., cardiotoxicity, hepatotoxicity and nephrotoxicity, in high PCB-exposed subjects. A few notable genes, such as BCL2, PON1, and ITGB1, were significantly altered in our study, and the related pathway analysis explained their plausible involvement in the respective disease processes, as mentioned. Our results provided insight into understanding the associated molecular mechanisms of complex gene-environment interactions in a PCB-exposed population. Future endeavors of supervised genotyping of pathway-specific molecular epidemiological studies and population biomarker validations are already underway to reveal individual risk factors in these PCB-exposed populations.

Serum PCB concentrations in relation to locally produced food items in eastern Slovakia.

Ingestion has been a primary route of PCB exposure for people, especially those not working directly in industrial settings. During 2002-2004, women were recruited at delivery from two districts in eastern Slovakia: Michalovce with high PCB contamination from a chemical manufacturing plant, and Svidnik located 70 km to the northwest, having lower environmental levels of PCBs. Concentrations of 15 PCB congeners were measured in maternal serum using high-resolution gas chromatography with electron capture detection. A food frequency questionnaire was developed and validated at the Research Institute of Nutrition and School of Medicine in Bratislava, Slovakia. The questionnaire was comprised of 88 food items representative of the national dietary habits and designed to ascertain (1) the source of food items as reported by the women (locally produced or purchased from a retail outlet) and (2) quantities consumed of high-fat food categories representative of the national dietary habits. Our primary goal was to identify specific food sources, either locally produced or purchased from retail stores, that might predict serum concentrations of PCBs. We used multiple linear regression to examine the relationship of dietary fats to lipid-adjusted serum PCB levels in 948 adult women (Michalovce N=662, Svidnik N=284) who had recently given birth. We adjusted for residential district, age, body mass index, education and duration of previous lactation. Consumption of fat from locally produced foods was significantly associated with higher levels of lipid-adjusted serum PCB (beta=0.06, P=0.007). Fat from foods purchased in retail outlets showed no significant association (beta=-0.02, P=0.36). There was no interaction between district and diet in predicting serum PCB levels. Comparing women in Michalovce consuming 20 g of fat per day from local sources with those consuming 1 g of fat per day from local sources, lipid-adjusted serum concentrations were predicted to be higher by 81 ng/g lipid or 14.8% 630 ng/g lipid versus 549 ng/g lipid.

Effect of managed care insurance on the use of preventive care for specific ethnic groups in the United States.

BACKGROUND: Ethnic disparities in access to health care is a persistent problem in the US. Despite the broad implementation of managed care, there is little information that specifically addresses how this type of coverage may affect ethnic disparities. OBJECTIVES: To examine the effect of managed care insurance on the use of preventive care for different ethnic groups. RESEARCH DESIGN: Observational cohort using the 1996 Medical Expenditure Panel Survey. SUBJECTS: Adults with health insurance who report their ethnicity as white, black, Hispanic, or Asian/Pacific Islander. MAIN OUTCOME MEASURES: (1) Mammography within the past 2 years for women between 50 and 75 years of age; (2) clinical breast exam within the past 2 years for women between 40 and 75 years; (3) Papanicolaou smear within the past 2 years for women between 18 and 65 years; and (4) cholesterol screening within the past 5 years for men and women older than the age of 20 years. RESULTS: Hispanic people enrolled in a managed care plan report higher rates of mammography, breast exam, and Papanicolaou smear compared with Hispanic people with fee-for-service insurance. For example, the adjusted predicted probability of a mammogram for Hispanic women with managed care was 85.6% compared with 72.4% for Hispanic women with fee-for-service coverage (risk difference: 13.2%; 95% CI for the risk difference 0.7%-25.7%). White persons with managed care are also more likely than white persons with fee-for-service coverage to receive mammography and cholesterol screening. Managed care is not associated with less preventive care for any ethnic group. CONCLUSIONS: In this nationally representative household survey, it was found that managed care is associated with greater use of some preventive care for Hispanic persons and white persons than fee-for-service insurance. Despite a focus on prevention, the benefits of managed care are not apparent for black persons or Asian/Pacific Islanders.

Is the prevalence of gatekeeping in a community associated with individual trust in medical care?

BACKGROUND: Consumer concerns about the restrictions of managed care may lead to distrust. OBJECTIVES: To examine whether a community's level of gatekeeping activity is associated with an individual's trust in medical care. RESEARCH DESIGN: Cross-sectional cohort (N = 49,929). SUBJECTS: Participants in a nationally representative sample derived from the Community Tracking Survey who had health insurance, had a usual source of care, made at least 1 physician visit, and resided in one of the sampled metropolitan areas with corresponding community-level data, including the prevalence of gatekeeping activity. MEASURES: Four questions measuring trust in physician. RESULTS: Individuals from communities with a higher prevalence of gatekeeping activity report less trust than individuals from areas with a lower prevalence of gatekeeping activity, after adjusting for whether that individual had a health plan with a gatekeeper requirement. For example, in communities with the highest prevalence of gatekeeping activity relative to the lowest, the odds ratio for individuals to agree strongly that they trusted their doctor to put their medical needs above all other considerations was 0.77 (95% confidence interval, 0.71-0.84). Also, a higher prevalence of gatekeeping in the community was positively associated with the perception that a physician was strongly influenced by insurance company rules when making decisions about medical care. Conversely, a higher prevalence of gatekeeping in the community was negatively associated with the perception that a doctor might perform an unnecessary test or procedure and with concern about restricted referral for specialty care. CONCLUSION: Individuals' trust in their physicians may be influenced by wider contextual variables, like the prevalence of gatekeeping in the community.

The association of race, socioeconomic status, and health insurance status with the prevalence of overweight among children and adolescents.

OBJECTIVES: We examined the effect of race, socioeconomic status, and health insurance status on the prevalence of overweight among children and adolescents. METHODS: We studied an observational cohort from the 1996 Medical Expenditure Panel Survey Household Component. RESULTS: In the younger group, both Black and Latino children had a greater likelihood of being overweight compared with White children. Among the adolescent group, Latinos and Asian/Pacific Islanders were more likely to be overweight. Among adolescents, lacking health insurance and having public insurance were both positively associated with the prevalence of overweight. A relationship between insurance status and overweight was not observed for younger children. CONCLUSIONS: There are substantial racial differences in the prevalence of overweight for children and adolescents. Health insurance status is associated with the prevalence of overweight among adolescents.

Variation in access to health care for different racial/ethnic groups by the racial/ethnic composition of an individual's county of residence.

BACKGROUND: Although the majority of studies examining racial/ethnic disparities in health care have focused on the characteristics of the individual, more recently there has been growing attention to the notion that an individual's health practices could be influenced by the characteristics of the place where they reside. OBJECTIVE: The objective of this study was to examine whether access to care for individuals of different racial/ethnic groups varies by the prevalence of blacks and the prevalence of Latinos in their county of residence. STUDY DESIGN: We conducted a cross-sectional cohort. PARTICIPANTS: Individuals from the 1996 Medical Expenditure Panel Survey, a nationally representative sample of U.S. households, who described their race/ethnicity as white, black, or Latino, and who resided in 1 of 677 counties (n = 14740) were studied. MEASURES: Counties were assigned to 6 groups based on the prevalence of blacks and Latinos who resided there (<6% referred to as "low prevalence," 6-39% referred to as "midprevalence," >or=40% referred to as "high prevalence" separately for both blacks and Latinos). Outcomes included whether during the past year any family members: 1). experienced difficulty obtaining any type of health care, delayed obtaining care, or did not receive health care they thought they needed (referred to as "difficulty obtaining care"); or (2). did not receive a doctor's care or a prescription medication because the family needed money to buy food, clothing, or pay for housing (referred to as "financial barriers"). RESULTS: After controlling for other individual and area-level covariates, blacks reported lower rates of both outcome variables when they lived in a county with a high prevalence of blacks compared with blacks who lived in a county with a low prevalence of blacks (difficulty obtaining care: 4.3% vs. 18.8%, P <0.005; financial barriers: 1.6% vs. 10.5%, P <0.005). There was a similar association for Latinos by the prevalence of Latinos in the county for difficulty obtaining care (high: 5.0% vs. low: 13.4%, P <0.05), but not the financial barriers outcome (high: 2.2% vs. low: 2.4%, P = 0.90). Whites who lived in an area with a high prevalence of Latinos were more likely to report both outcomes compared with whites who lived in a county with a low prevalence of Latinos (difficulty obtaining care: 17.7% vs. 9.4%, P <0.05; financial barriers: 8.5% vs. 3.2%, P <0.005) . CONCLUSIONS: Blacks and Latinos may perceive fewer barriers to care when they live in a county with a high prevalence of people of similar race/ethnicity. Conversely, whites may perceive more difficulty receiving care when they live in an area with a high prevalence of Latinos. Diminishing disparities in access to health care may require interventions that extend beyond the individual.