Prenatal and childhood lead exposure is prospectively associated with biological markers of aging in adolescence.

Few studies have related early life lead exposure to adolescent biological aging, a period characterized by marked increases in maturational tempo. We examined associations between prenatal and childhood lead exposure and adolescent biological age (mean 14.5 years) utilizing multiple epigenetic clocks including: intrinsic (IEAA), extrinsic (EEAA), Horvath, Hannum, PhenoAge, GrimAge, Skin-Blood, Wu, PedBE, as well as DNA methylation derived telomere length (DNAmTL). Epigenetic clocks and DNAmTL were calculated via adolescent blood DNA methylation measured by Infinium MethylationEPIC BeadChips. We constructed general linear models (GLMs) with individual lead measures predicting biological age. We additionally examined sex-stratified models and lead by sex interactions, adjusting for adolescent age and lead levels, maternal smoking and education, and proportion of cell types. We also estimated effects of lead exposure on biological age using generalized estimating equations (GEE). First trimester blood lead was positively associated with a 0.14 increase in EEAA age in the GLMs though not the GEE models (95%CI 0.03, 0.25). First and 2nd trimester blood lead levels were associated with a 0.02 year increase in PedBE age in GLM and GEE models (1st trimester, 95%CI 0.004, 0.03; 2nd trimester, 95%CI 0.01, 0.03). Third trimester and 24 month blood lead levels were associated with a -0.06 and -0.05 decrease in Skin-Blood age, respectively, in GLM models. Additionally, 3rd trimester blood lead levels were associated with a 0.08 year decrease in Hannum age in GLM and GEE models (95%CI -0.15, -0.01). There were multiple significant results in sex-stratified models and significant lead by sex interactions, where males experienced accelerated biological age, compared to females who saw a decelerated biological age, with respect to IEAA, EEAA, Horvath, Hannum, and PedBE clocks. Further research is needed to understand sex-specific relationships between lead exposure and measures of biological aging in adolescence and the trajectory of biological aging into young adulthood.

Lead exposure, glucocorticoids, and physiological stress across the life course: A systematic review.

The biological pathways linking lead exposure to adverse outcomes are beginning to be understood. Rodent models suggest lead exposure induces dysfunction within the hypothalamic-pituitary-adrenal (HPA) axis and glucocorticoid regulation, a primary physiological stress response system. Over time, HPA axis and glucocorticoid dysfunction has been associated with adverse neurocognitive and cardiometabolic health, much like lead exposure. This systematic review utilized PRISMA guidelines to synthesize the literature regarding associations between lead exposure and downstream effector hormones of the HPA axis, including cortisol, a glucocorticoid, and dehydroepiandrosterone (DHEA), a glucocorticoid antagonist. We additionally determined the state of the evidence regarding lead exposure and allostatic load, a measure of cumulative body burden resultant of HPA axis and glucocorticoid dysfunction. A total of 18 articles were included in the review: 16 assessed cortisol or DHEA and 3 assessed allostatic load. Generally, the few available child studies suggest a significant association between early life lead exposure and altered cortisol, potentially suggesting the impact of developmental exposure. In adulthood, only cross sectional studies were available. These reported significant associations between lead and reduced cortisol awakening response and increased cortisol reactivity, but few associations with fasting serum cortisol. Two studies reported significant associations between increasing lead exposure and allostatic load in adults and another between early life lead exposure and adolescent allostatic load. The paucity of studies examining associations between lead exposure and allostatic load or DHEA and overall heterogeneity of allostatic load measurements limit conclusions. However, these findings cautiously suggest associations between lead and dysregulation of physiological stress pathways (i.e., glucocorticoids) as seen through cortisol measurement in children and adults. Future research would help to elucidate these associations and could further examine the physiological stress pathway as a mediator between lead exposure and detrimental health outcomes.

Associations of prenatal and childhood Pb exposure with allostatic load in adolescence: Findings from the ELEMENT cohort study.

The biological pathways which link lead (Pb) and long-term outcomes are unclear, though rodent models and a few human studies suggest Pb may alter the body's stress response systems, which over time, can elicit dysregulated stress responses with cumulative impacts. This study examined associations between prenatal and early childhood Pb exposure and adolescent allostatic load, an index of an individual's body burden of stress in multiple biological systems, and further examined sex-based associations. Among 391 (51% male) participants in the ELEMENT birth cohort, we related trimester-specific maternal blood Pb, 1-month postpartum maternal tibia and patella Pb, and child blood Pb at 12-24 months to an allostatic load index in adolescence comprised of biomarkers of cardiovascular, metabolic, neuroendocrine, and immune function. The results were overall mixed, with prenatal exposure, particularly maternal bone Pb, being positively associated with allostatic load, and early childhood Pb showing mixed results for males and females. In adjusted Poisson regression models, 1 mcg/g increase in tibia Pb was associated with a 1% change in expected allostatic load (IRR = 1.01; 95%CI 0.99, 1.02). We found a significant Pb × sex interaction (IRR = 1.05; 95%CI 1.01, 1.10); where males saw an increasing percent change in allostatic load as 12 month Pb levels increased compared to females who saw a decreasing allostatic load. Further examination of allostatic load will facilitate the determination of potential mechanistic pathways between developmental toxicant exposures and later-in-life cardiometabolic outcomes.

Overweight and obesity status from the prenatal period to adolescence and its association with non-alcoholic fatty liver disease in young adults: cohort study.

OBJECTIVE: To examine the associations of maternal and child overweight status across multiple time-points with liver fat content in the offspring during young adulthood. DESIGN: Cohort study. SETTING: ELEMENT Cohort in Mexico City. POPULATION: Pregnant women with singleton births (n = 97). METHODS: We quantified hepatic triglyceride content (liver fat content) by proton magnetic resonance spectroscopy (1H MRS) and conventional T2-weighted MRIs (3T scanner) in 97 young adults from the ELEMENT birth cohort in Mexico City. Historical records of the cohort were used as a source of pregnancy, and childhood and adolescence anthropometric information, overweight and obesity (OWOB) were defined. Adjusted structural equation models were run to identify the association between OWOB in different life stages with liver fat content (log-transformed) in young adulthood. MAIN OUTCOME: Maternal OWOB at the time of delivery was directly and indirectly associated with the liver fat content in the offspring at young adulthood. RESULTS: Seventeen percent of the participants were classified as having NAFLD. We found a strong association of OWOB between all periods assessed. Maternal OWOB at time of delivery (ß = 1.97, 95% CI 1.28-3.05), and OWOB status in the offspring at young adulthood (ß = 3.17, 95% CI 2.10-4.77) were directly associated with the liver fat content in the offspring. Also, maternal OWOB was indirectly associated with liver fat content through offspring OWOB status. CONCLUSION: We found that maternal OWOB status is related to fatty liver content in the offspring as young adults, even after taking into account OWOB status and lifestyle factors in the offspring. TWEETABLE ABSTRACT: There was an association between pre-pregnancy overweight and the development of NAFLD in adult offspring.

Diurnal cortisol and obesity in adolescents with and without Down syndrome.

BACKGROUND: The prevalence of obesity in adolescents with Down syndrome (DS) far exceeds that in the general population. Cortisol, an adrenal hormone, can be obesogenic when dysregulated. However, the diurnal patterns of this hormone have not been examined among individuals with DS. Variations in adiposity may also mediate cortisol regulation. This study sought to examine diurnal cortisol patterns in adolescents with DS as well as associations between cortisol function and obesity. METHOD: A total of 32 adolescents, including 16 with DS and 16 controls with typical development (TD) of similar sex, age and Tanner pubertal stage (P > 0.05), participated in this preliminary study. Participants completed a dual-energy X-ray absorptiometry scan to measure body composition and collected saliva samples for cortisol measurements in the morning, afternoon and night. Linear mixed models with random intercepts and repeated measures were used to examine the daily trajectory of log-transformed cortisol concentrations between adolescents with and without DS. A second model examined the interaction between DS and presence of elevated body fatness. RESULTS: Adolescents with DS had higher morning cortisol concentrations (intercept = 0.37 µg/dL), but this was not significantly different than in TD (0.35 µg/dL, P = 0.16). Cortisol significantly declined across hours (b = -0.026 µg/dL/h, P < 0.001), but this decline also did not differ from that observed in TD (b = -0.024 µg/dL/h, P = 0.43). While cortisol levels were slightly higher among adolescents with elevated body fatness, this difference was not statistically significant (P > 0.05; d = 0.30). CONCLUSIONS: This study is the first to examine diurnal cortisol in DS but is limited in sample size. These preliminary findings suggest that diurnal cortisol patterns are not significantly different between adolescents with DS and TD and that cortisol levels are not associated with adiposity in this population. Despite these non-significant differences, youth with DS continue to be an 'at-risk' population for paediatric obesity in need of clinical intervention.

Prenatal lead exposure in relation to age at menarche: results from a longitudinal study in Mexico City.

Animal and cross-sectional epidemiological studies suggest that prenatal lead exposure is related to delayed menarche, but this has not been confirmed in longitudinal studies. We analyzed this association among 200 girls from Mexico City who were followed since the first trimester of gestation. Maternal blood lead levels were analyzed once during each trimester of pregnancy, and daughters were asked about their first menstrual cycle at a visit between the ages of 9.8 and 18.1 years. We estimated hazard ratios (HRs) and 95% confidence intervals (CI) for probability of menarche over the follow-up period using interval-censored Cox models, comparing those with prenatal blood lead level ⩾5 µg/dl to those with prenatal blood lead <5 µg/dl. We also estimated HRs and 95% CI with conventional Cox regression models, which utilized the self-reported age at menarche. In adjusted analyses, we accounted for maternal age, maternal parity, maternal education, and prenatal calcium treatment status. Across trimesters, 36-47% of mothers had blood lead levels ⩾5 µg/dl. Using interval-censored models, we found that during the second trimester only, girls with ⩾5 µg/dl prenatal blood lead had a later age at menarche compared with girls with prenatal blood lead levels <5 µg/dl (confounder-adjusted HR=0.59, 95% CI 0.28-0.90; P=0.05). Associations were in a similar direction, although not statistically significant, in the conventional Cox regression models, potentially indicating measurement error in the self-recalled age at menarche. In summary, higher prenatal lead exposure during the second trimester could be related to later onset of sexual maturation.

Maternal intake of omega-3 and omega-6 polyunsaturated fatty acids during mid-pregnancy is inversely associated with linear growth.

This study investigates relations of maternal N-3 and N-6 polyunsaturated fatty acids (PUFA) intake during pregnancy with offspring body mass index (BMI), height z-score and metabolic risk (fasting glucose, C-peptide, leptin, lipid profile) during peripuberty (8-14 years) among 236 mother-child pairs in Mexico. We used food frequency questionnaire data to quantify trimester-specific intake of N-3 alpha-linolenic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); N-6 linoleic acid and arachidonic acid (AA); and N-6:N-3 (AA:EPA+DHA), which accounts for the fact that the two PUFA families have opposing effects on physiology. Next, we used multivariable linear regression models that accounted for maternal education and parity, and child's age, sex and pubertal status, to examine associations of PUFA intake with the offspring outcomes. In models where BMI z-score was the outcome, we also adjusted for height z-score. We found that higher second trimester intake of EPA, DHA and AA were associated with lower offspring BMI and height z-score. For example, each 1-s.d. increment in second trimester EPA intake corresponded with 0.25 (95% CI: 0.03, 0.47) z-scores lower BMI and 0.20 (0.05, 0.36) z-scores lower height. Accounting for height z-score in models where BMI z-score was the outcome attenuated estimates [e.g., EPA: -0.16 (-0.37, 0.05)], suggesting that this relationship was driven by slower linear growth rather than excess adiposity. Maternal PUFA intake was not associated with the offspring metabolic biomarkers. Our findings suggest that higher PUFA intake during mid-pregnancy is associated with lower attained height in offspring during peripuberty. Additional research is needed to elucidate mechanisms and to confirm findings in other populations.

Exposure to Bisphenol A and phthalates metabolites in the third trimester of pregnancy and BMI trajectories.

BACKGROUND: Bisphenol A (BPA) and phthalates metabolites are linked to a variety of adverse health consequences but studies have not explored their association with growth trajectories. OBJECTIVE: Explore body mass index (BMI) trajectories for tertile exposures to BPA and phthalates metabolites in the third trimester of pregnancy. METHODS: We constructed BMI (kg/m2 ) trajectories from birth to 14 years in a birth cohort of 249 children from Mexico City using tertiles of third trimester maternal urinary concentrations of BPA and phthalates metabolites. Fractional age polynomials and mixed effects models were fit separately by sex. Predicted models were plotted for each metabolite tertile with the covariates mother's education and BMI centered at average values. RESULTS: Highest predicted BMI trajectories for female children were observed for third tertile exposure to the phthalate metabolite mono(2-ethyl-5-carboxypentyl) phthalate. In male children, first tertile exposure to mono-isobutyl phthalate and monobenzyl phthalate and second tertile exposure to mono(2-ethylhexyl) phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate predicted the highest BMI trajectory by adolescence. There was no relationshsip between BPA and child growth trajectory. CONCLUSIONS: These results suggest sex-specific differences in BMI trajectories by levels of metabolite exposure. Additional studies are needed to consider growth through adolescence in assessing the association of pregnancy exposures on child's BMI.

Birth order and sibship composition as predictors of overweight or obesity among low-income 4- to 8-year-old children.

OBJECTIVE: This study aimed to examine the association of birth order and number and sex of siblings with overweight or obesity among 4- to 8-year-olds. METHODS: This is a cross-sectional study involving 273 low-income mother-child dyads. Questionnaires and anthropometry were completed. Multiple logistic regression was used to examine the association of birth order, having younger siblings, having older siblings, having at least one brother and having at least one sister with odds of overweight or obesity. Analyses were repeated to additionally include non-biological siblings. Models were adjusted for potential confounders and intermediate variables. RESULTS: Prevalence of child overweight or obesity was 42.5%. Adjusting for covariates, only children and youngest siblings had higher odds of overweight or obesity compared with oldest siblings (odds ratio [OR]: 4.18, 95% confidence interval [CI]: 1.67, 10.46 and OR: 3.21, 95% CI: 1.41, 7.33, respectively). Having one or more younger siblings and having at least one brother were associated with lower odds (OR: 0.38, 95% CI: 0.21, 0.69 and OR: 0.47, 95% CI: 0.28, 0.81, respectively). Including non-biological siblings did not meaningfully change the associations. CONCLUSION: Birth order and sibship composition are associated with overweight or obesity among 4- to 8-year-olds. Future studies identifying the underlying behavioural mechanism can help inform family-based intervention programmes.

Childhood overweight and maternal depressive symptoms.

AIM: Given the rising global prevalence of overweight associated with the nutrition transition, the objective of this study was to evaluate whether maternal depressive symptoms are related to overweight in infants aged 6-24 months. METHODS: Participants in this cross-sectional study included 589 mother-child dyads from low-income urban communities in Teresina, Piauí, northeast Brazil. While adjusting for sociodemographic and biological determinants of child growth, the study assessed the relationship between mothers' depressive symptom scores, measured with the Center for Epidemiologic Studies Depression Scale and child weight-for-height using multivariable logistic regression. Child overweight was calculated with the World Health Organization growth curves using 85th and 95th percentile cutoffs of the weight-for-height z-score (WHZ). RESULTS: Children of mothers with high depressive symptoms had 1.7 and 2.3 higher odds of being over WHZ cutoffs for the 85th and 95th percentile, respectively. Child age between 18 and 24 months (compared with children 6-12 months old), being low birth weight, not receiving the Family Health Programme and breastfeeding between 6 and 12 months (compared with <6 months) were other factors inversely related to at least one of the overweight indicators (odds ratio (OR) range 0.3 to 0.6). Having a mother with fewer than 8 years of education was positively associated with child overweight (OR 1.4, 95% CI 1.0 to 2.1, for WHZ >85th%). CONCLUSION: Results suggest that maternal depressive symptoms are related to overweight in children aged 6-24 months.

Coexistence of maternal central adiposity and child stunting in Mexico.

OBJECTIVE: To assess the coexistence of maternal adiposity and child stunting (CS) in Mexico, estimate its national prevalence and identify the associated socio-demographic factors. METHODS: A secondary analysis from the Mexican Nutrition Survey 1999, a nationally representative survey, was conducted. Mother and children subsamples were matched and a total of 6225 mother/child pairs were obtained. Stunting was defined as height-for-age z-scores <-2.0. Maternal body mass index (BMI) was classified according to World Health Organization recommended cutoff points. Waist-to-hip ratio (WHR) was calculated by dividing waist by hip circumferences. Logistic regression models were fitted to explore the coexistence of CS and maternal central adiposity (MCA) (WHR> or =0.85) while controlling for biological and socio-demographic factors. RESULTS: A total of 5974 pairs had complete information. MCA coexisted with CS in 6.2% of the mother/child pairs. The phenomenon was more prevalent in rural locations, in the south region and among indigenous families (14.5, 12.5 and 23.9%). After controlling for child age and maternal BMI, a 78% increase in the likelihood of CS was related to maternal WHR > or =0.85 (odds ratio (OR)=1.78, 95% confidence interval (CI)=1.53, 2.10). After controlling for maternal height, the magnitude of the OR decreased (OR=1.33, 95%CI=1.13, 1.57), but remained significant. Therefore, it is suggested that women with a WHR approximately 1 have had twice the probability of having a stunted child as those with a WHR of 0.65. CONCLUSION: Although MCA and CS are two conditions frequently regarded as result of opposite determinants, our observation suggests that this is not necessarily the case, particularly in populations undergoing the nutrition transition. MCA was associated not only to chronic diseases, but also to child stunting.

Influence of proinflammatory cytokines and chemokines on the neuropathogenesis of oncornavirus and immunosuppressive lentivirus infections.

Retroviral infection of the CNS can lead to severe debilitating neurological diseases in humans and other animals. Four general types of pathogenic effects with various retroviruses have been observed including: hemorrhage (TR1.3), spongiform encephalopathy (CasBrE, FrCasE, PVC211, NT40, Mol-ts1), demyelination with inflammatory lesions (HTLV-1, visna, CAEV), and encephalopathy with gliosis and proinflammatory chemokines and cytokines, usually with microglial giant cells and nodules [human immunodeficiencyvirus (HIV), feline immunodeficiencyvirus (FIV), simian immunodeficiency virus (SIV), Fr98]. This review focuses on this fourth group of retroviruses. In this latter group, proinflammatory cytokine and chemokine upregulation accompanies the disease process, and may influence pathogenesis by direct effects on resident CNS cells. The review first discusses the Fr98 murine polytropic virus system with particular reference to the roles of cytokines and chemokines in the pathogenic process. The Fr98 data are then compared and contrasted to the cytokine and chemokine data in the lentivirus systems, HIV, SIV, and FIV. Finally, various mechanisms are presented by which tumor necrosis factor (TNF) and several chemokines may alter the pathogenesis of retrovirus infection of the CNS.

Design of an intervention addressing multiple levels of influence on dietary and activity patterns of low-income, postpartum women.

Low-income, multi-ethnic women are at elevated risk for obesity and chronic diseases, yet influences at different levels may act as barriers to changing risk behaviors. Following the birth of a child, childrearing and social isolation can exacerbate these influences. The social ecological framework integrates behavior-change strategies at different levels, providing a strong theoretical base for developing interventions in this high-risk population. The primary purpose of this randomized controlled trial is to test the efficacy of an educational model delivered by community-based paraprofessionals in improving diet, activity and weight loss among new mothers over a 12-month postpartum period and a 6-month maintenance period. This model fosters institutional change to support behavior changes influenced at intrapersonal and interpersonal levels, through collaboration with federal programs for low-income families: the Special Supplemental Food Program for Women, Infants and Children (WIC), and the Expanded Food and Nutrition Education Program (EFNEP). Participants are randomized to the Usual Care, e.g. WIC nutrition and breastfeeding education, or Enhanced EFNEP intervention arm, consisting of Usual WIC Care plus a sustained, multi-component intervention including home visits, group classes and monthly telephone counseling. If shown to be efficacious, this program will be readily sustainable through existing federal agencies.

HIV status and sociodemographic correlates of maternal body size and wasting during pregnancy.

OBJECTIVE: To examine HIV status and sociodemographic variables as correlates of body size (height, body mass index (BMI), and mid-upper-arm circumference (MUAC)) and wasting (MUAC <22 cm) in pregnant women. DESIGN: Cross-sectional study. SETTING: Four antenatal clinics in Dar es Salaam, Tanzania. SUBJECTS: Women presenting for first prenatal visit before the 23rd week of gestation, between April 1995 and July 1997 (n=13 760). RESULTS: Mean MUAC, BMI and height were 25.5 cm, 23.5 kg/m(2) and 155.1 cm, respectively. The prevalence of HIV infection was 13.1% and the overall prevalence of wasting was 4.7%. Wasting was 34% (95% CI=3%, 73%) more prevalent among HIV-infected than in uninfected mothers, after adjusting for week of gestation, height and sociodemographic indicators. The risk of wasting associated with HIV infection was highest among women with low level of education or unable to contribute to the household income. From a multiple linear regression model, BMI was positively associated with mother's age, level of education and money spent on food, but not with HIV infection, after adjusting for week of gestation. In multivariate analysis, height increased monotonically by categories of maternal age and level of education, and was also positively correlated with the ability to contribute to household income, the amount of money spent on food per person per day, and having a professional partner. CONCLUSION: HIV infection is a significant risk factor for wasting among pregnant women, particularly in groups of low socioeconomic status (SES). SES indicators are strongly correlated with maternal height and with BMI during the first and second trimesters of pregnancy independently of HIV status. SPONSORSHIP: The National Institute of Child Health and Human Development (NICHD R01 32257), and the Fogarty International Center (NIH D43 TW00004).

The effect of social desirability trait on self-reported dietary measures among multi-ethnic female health center employees.

PURPOSE: To evaluate the effect of social desirability trait, the tendency to respond in a manner consistent with societal expectations, on self-reported fruit, vegetable, and macronutrient intake. METHODS: A 61-item food frequency questionnaire (FFQ), 7-item fruit and vegetable screener, and a single question on combined fruit and vegetable intake were completed by 132 female employees at five health centers in eastern Massachusetts. Intake of fruit and vegetables derived from all three methods and macronutrients from the FFQ were fit as dependent variables in multiple linear regression models (overall and by race/ethnicity and education); independent variables included 3-day mean intakes derived from 24-hour recalls (24HR) and score on the 33-point Marlowe-Crowne Social Desirability scale (the regression coefficient for which reflects its effect on estimates of dietary intake based on the comparison method relative to 24HR). RESULTS: Results are based on the 93 women with complete data and FFQ-derived caloric intake between 450 and 4500 kcal/day. In women with college education, FFQ-derived estimates of total caloric were associated with under-reporting by social desirability trait (e.g., the regression coefficient for total caloric intake was -23.6 kcal/day/point in that group versus 36.1 kcal/day/point in women with education less than college) (difference = 59.7 kcal/day/point, 95% confidence interval (CI) = 13.2, 106.2). Except for the single question on which women with college education tended to under-report (difference =.103 servings/day/point, 95% CI = 0.003, 0.203), there was no association of social desirability trait with self-reported fruit and vegetable intake. CONCLUSIONS: The effect of social desirability trait on FFQ reports of macronutrient intake appeared to differ by education, but not by ethnicity or race. The results of this study may have important implications for epidemiologic studies of diet and health in women.

Immunosuppression by CD4+ regulatory T cells induced by chronic retroviral infection.

Normal levels of CD4(+) regulatory T cells are critical for the maintenance of immunological homeostasis and the prevention of autoimmune diseases. However, we now show that the expansion of CD4(+) regulatory T cells in response to a chronic viral infection can lead to immunosuppression. Mice persistently infected with Friend retrovirus develop approximately twice the normal percentage of splenic CD4(+) regulatory T cells and lose their ability to reject certain tumor transplants. The role of CD4(+) regulatory T cells was demonstrated by the transmission of immunosuppression to uninfected mice by adoptive transfers of CD4(+) T cells. CD4(+) T cells from chronically infected mice were also immunosuppressive in vitro, inhibiting the generation of cytolytic T lymphocytes in mixed lymphocyte cultures. Inhibition occurred at the level of blast-cell formation through a mechanism or mechanisms involving transforming growth factor-beta and the cell surface molecule CTLA-4 (CD152). These results suggest a possible explanation for HIV- and human T cell leukemia virus-I-induced immunosuppression in the absence of T cell depletion.

Effect of maternal lead burden on infant weight and weight gain at one month of age among breastfed infants.

INTRODUCTION: Transfer of lead from bone to the bloodstream increases during lactation. However, the effect of maternal lead burden on growth in breastfed newborns is still unknown. This study examined early postnatal growth in a cohort of healthy breastfed newborns in relation to maternal bone lead burden. METHODS: Lead levels were measured among 329 mother-infant pairs in umbilical cord blood at birth and in maternal and infant venous blood at 1 month postpartum. Maternal evaluations at 1 month postpartum included lead measures in blood and bone (measured in the tibia and the patella). Blood lead was determined by graphite furnace atomic absorption spectrophotometry. Bone lead was measured by (109)Cd Kx-radiograph fluorescence instrument. The primary endpoints were attained weight 1 month of age, and weight gain from birth to 1 month of age, which were analyzed in relation to lead biomarkers and relevant covariates by linear regression models. RESULTS: Infants studied had an average weight gain of 33.1 g/day (standard deviation [SD] = 11.6). Mean infant (at 1 month of age) and maternal blood lead levels were 5.6 microg/dL (SD = 3.0) and 9.7 microg/dL (SD = 4.1), respectively. Mean maternal bone lead levels were 10.1 microg of lead/g (SD = 10.3) and 15.29 microg of lead/g (SD = 15.2) of bone mineral for tibia and patella, respectively. Infant blood lead levels were inversely associated with weight gain, with an estimated decline of 15.1 g per microg/dL of blood lead. Children who were exclusively breastfed had significantly higher weight gains; however, this gain decreased significantly with increasing levels of patella lead. The multivariate regression analysis predicted a 3.6-g decrease in weight at 1 month of age per microg of lead per gram bone mineral increase in maternal patella lead levels. CONCLUSIONS: Maternal lead burden is negatively associated to infant attained weight at 1 month of age and to postnatal weight gain from birth to 1 month of age. Additional studies are needed to better understand this source of exposure and to develop interventions to minimize its impact.

Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis.

BACKGROUND: The rising prevalence of obesity in children has been linked in part to the consumption of sugar-sweetened drinks. Our aim was to examine this relation. METHODS: We enrolled 548 ethnically diverse schoolchildren (age 11.7 years, SD 0.8) from public schools in four Massachusetts communities, and studied them prospectively for 19 months from October, 1995, to May, 1997. We examined the association between baseline and change in consumption of sugar-sweetened drinks (the independent variables), and difference in measures of obesity, with linear and logistic regression analyses adjusted for potentially confounding variables and clustering of results within schools. FINDINGS: For each additional serving of sugar-sweetened drink consumed, both body mass index (BMI) (mean 0.24 kg/m2; 95% CI 0.10-0.39; p=0.03) and frequency of obesity (odds ratio 1.60; 95% CI 1.14-2.24; p=0.02) increased after adjustment for anthropometric, demographic, dietary, and lifestyle variables. Baseline consumption of sugar-sweetened drinks was also independently associated with change in BMI (mean 0.18 kg/m2 for each daily serving; 95% CI 0.09-0.27; p=0.02). INTERPRETATION: Consumption of sugar-sweetened drinks is associated with obesity in children.

Head lice resistance: itching that just won't stop.

OBJECTIVE: To evaluate the reports of resistance and cross-resistance to pediculicides in the head louse (Pediculus capitis), as well as the mechanisms involved. DATA SOURCES: Literature identified through a MEDLINE search (1966-April 2000) and through other secondary literature databases and/or bibliographies of pertinent articles. DATA SYNTHESIS: Head lice infestation is a common, worldwide problem. The widespread use of insecticide treatments together with inadequate treatment methods has led to a concern regarding the potential development of resistant head lice. This literature review examines the reports of resistance of the head louse as well as the purported mechanisms involved. CONCLUSIONS: Current research suggests that head lice resistance exists, but little is known regarding the actual incidence of this resistance or whether this incidence is increasing. More research is needed to assess the status of this problem. Proposed mechanisms for head lice resistance include knock-down resistance, glutathione S-transferase-based resistance, and monooxygenase-based resistance.

Differences in cytokine and chemokine responses during neurological disease induced by polytropic murine retroviruses Map to separate regions of the viral envelope gene.

Infection of the central nervous system (CNS) by several viruses can lead to upregulation of proinflammatory cytokines and chemokines. In immunocompetent adults, these molecules induce prominent inflammatory infiltrates. However, with immunosuppressive retroviruses, such as human immunodeficiency virus (HIV), little CNS inflammation is observed yet proinflammatory cytokines and chemokines are still upregulated in some patients and may mediate pathogenesis. The present study examined expression of cytokines and chemokines in brain tissue of neonatal mice infected with virulent (Fr98) and avirulent (Fr54) polytropic murine retroviruses. While both viruses infect microglia and endothelia primarily in the white matter areas of the CNS, only Fr98 induces clinical CNS disease. The pathology consists of gliosis with minimal morphological changes and no inflammation, similar to HIV. In the present experiments, mice infected with Fr98 had increased cerebellar mRNA levels of proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha), TNF-beta, and interleukin-1 alpha and chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, monocyte chemoattractant protein 1 (MCP-1), gamma-interferon-inducible protein 10 (IP-10), and RANTES compared to mice infected with Fr54 or mock-infected controls. The increased expression of these genes occurred prior to the development of clinical symptoms, suggesting that these cytokines and chemokines might be involved in induction of neuropathogenesis. Two separate regions of the Fr98 envelope gene are associated with neurovirulence. CNS disease associated with the N-terminal portion of the Fr98 env gene was preceded by upregulation of cytokines and chemokines. In contrast, disease associated with the central region of the Fr98 env gene showed no upregulation of cytokines or chemokines and thus did not require increased expression of these genes for disease induction.