Faculty Bibliography

BACKGROUND: Socioeconomic analysis is currently used in the Europe Union as part of the regulatory process in Regulation Registration, Evaluation and Authorisation of Chemicals (REACH), with the aim of assessing and managing risks from dangerous chemicals. The political impact of the socio-economic analysis is potentially high in the authorisation and restriction procedures, however, current socio-economic analysis dossiers submitted under REACH are very heterogeneous in terms of methodology used and quality. Furthermore, the economic literature is not very helpful for regulatory purposes, as most published calculations of health costs associated with chemical exposures use epidemiological studies as input data, but such studies are rarely available for most substances. The quasi-totality of the data used in the REACH dossiers comes from toxicological studies. METHODS: This paper assesses the use of the integrated probabilistic risk assessment, based on toxicological data, for the calculation of health costs associated with endocrine disrupting effects of triclosan. The results are compared with those obtained using the population attributable fraction, based on epidemiological data. RESULTS: The results based on the integrated probabilistic risk assessment indicated that 4894 men could have reproductive deficits based on the decreased vas deferens weights observed in rats, 0 cases of changed T3 levels, and 0 cases of girls with early pubertal development. The results obtained with the Population Attributable Fraction method showed 7,199,228 cases of obesity per year, 281,923 girls per year with early pubertal development and 88,957 to 303,759 cases per year with increased total T3 hormone levels. The economic costs associated with increased BMI due to TCS exposure could be calculated. Direct health costs were estimated at euro5.8 billion per year. CONCLUSIONS: The two methods give very different results for the same effects. The choice of a toxicological-based or an epidemiological-based method in the socio-economic analysis will therefore significantly impact the estimated health costs and consequently the political risk management decision. Additional work should be done for understanding the reasons of these significant differences.

Context: Common environmental contaminants can disrupt normal thyroid function, which plays essential but varying roles at different ages. Objective: To evaluate the relationship of perchlorate, thiocyanate, and nitrate, three sodium-iodide symporter (NIS) inhibitors, and thyroid function in different age-sex-stratified populations. Design, Setting, Participants, and Intervention: This was a cross-sectional analysis of data from the 2009-2012 National Health and Nutrition Examination Surveys (NHANES) evaluating the exposure to perchlorate, thiocyanate, and nitrate in 3,151 participants aged 12-80. Main Outcome Measure: Blood serum free thyroxine (FT4) as both a continuous and categorical variable. We also assessed blood serum thyroid stimulating hormone (TSH). Results: Controlling for serum cotinine, BMI, total daily energy consumption, race/ethnicity, and poverty-to-income ratio, for each log unit increase in perchlorate, FT4 decreased by 0.03 ng/dL in both the general population (p=0.004) and in all women (p=0.005), and by 0.06 ng/dL in adolescent girls (p=0.029), corresponding to 4% and 8% decreases relative to median FT4, respectively. For each log unit increase thiocyanate, FT4 decreased by 0.07 ng/dL in adolescent boys (p=0.003), corresponding to a 9% decrease relative to median FT4, respectively. Conclusions: Our results indicate that adolescent boys and girls represent vulnerable subpopulations to the thyroid-blocking effects of NIS symporter inhibitors. These results suggest a valuable screening and intervention opportunity.

BACKGROUND: Previous studies identified associations between maternal obesity and childhood neurodevelopment, but few examined paternal obesity despite potentially distinct genetic/epigenetic effects related to developmental programming. METHODS: Upstate KIDS (2008-2010) recruited mothers from New York State (excluding New York City) at approximately 4 months postpartum. Parents completed the Ages and Stages Questionnaire (ASQ) when their children were 4, 8, 12, 18, 24, 30, and 36 months of age corrected for gestation. The ASQ is validated to screen for delays in 5 developmental domains (ie, fine motor, gross motor, communication, personal-social functioning, and problem-solving ability). Analyses included 3759 singletons and 1062 nonrelated twins with >/=1 ASQs returned. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated by using generalized linear mixed models accounting for maternal covariates (ie, age, race, education, insurance, marital status, parity, and pregnancy smoking). RESULTS: Compared with normal/underweight mothers (BMI <25), children of obese mothers (26% with BMI >/=30) had increased odds of failing the fine motor domain (aOR 1.67; confidence interval 1.12-2.47). The association remained after additional adjustment for paternal BMI (1.67; 1.11-2.52). Paternal obesity (29%) was associated with increased risk of failing the personal-social domain (1.75; 1.13-2.71), albeit attenuated after adjustment for maternal obesity (aOR 1.71; 1.08-2.70). Children whose parents both had BMI >/=35 were likely to additionally fail the problem-solving domain (2.93; 1.09-7.85). CONCLUSIONS: Findings suggest that maternal and paternal obesity are each associated with specific delays in early childhood development, emphasizing the importance of family information when screening child development.

In a longitudinal population-based study of 2,905 children, we investigated if infants' neuromotor development was associated with autistic traits in childhood. Overall motor development and muscle tone were examined by trained research assistants with an adapted version of Touwen's Neurodevelopmental Examination between ages 2 and 5 months. Tone was assessed in several positions and items were scored as normal, low, or high tone. Parents rated their children's autistic traits with the Social Responsiveness Scale (SRS) and the Pervasive Developmental Problems (PDP) subscale of the Child Behavior Checklist at 6 years. We defined clinical PDP if scores were >98th percentile of the norm population. Diagnosis of autism spectrum disorder (ASD) was clinically confirmed in 30 children. We observed a modest association between overall neuromotor development in infants and autistic traits. Low muscle tone in infancy predicted autistic traits measured by SRS (adjusted beta = 0.05, 95% CI for B: 0.00-0.02, P = 0.01), and PDP (adjusted beta = 0.08, 95% CI for B: 0.04-0.10, P < 0.001). Similar results emerged for the association of low muscle tone and clinical PDP (adjusted OR = 1.36, 95% CI: 1.08-1.72, P = 0.01) at age 6 years. Results remained unchanged if adjusted for child intelligence. There was no association between high muscle tone and SRS or PDP. Exclusion of children with ASD diagnosis did not change the association. This large study showed a prospective association of infant muscle tone with autistic traits in childhood. Our findings suggest that early detection of low muscle tone might be a gateway to improve early diagnosis of ASD. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.

INTRODUCTION: Prenatal smoking exposure may lead to permanent changes in neonatal inflammation and immune response that have lifelong implications, including increased risks for atopy and respiratory disorders. METHODS: The effect of maternal smoking on neonatal biomarkers of inflammation and immune response was assessed among 3459 singletons and twins in the Upstate KIDS Study. The following inflammatory biomarkers were measured using newborn dried blood spots (DBSs): interleukin (IL)-1alpha, IL-1 receptor antagonist, IL-6, IL-8, C-reactive protein, and tumor necrosis factor alpha. Immunoglobulins (IgE, IgA, IgM, and IgG subclasses) were also assessed. We used generalized estimating equations to calculate mean differences (beta) in biomarker levels by timing of pregnancy smoking, cigarette load, and secondhand smoke exposure after adjusting for sociodemographic and lifestyle factors including maternal body mass index. RESULTS: Of the 344 (12%) women reporting smoking during pregnancy, about 40% continued throughout pregnancy and 13% reported smoking more than 1 pack per day. After covariate adjustment and Bonferroni correction for multiple comparisons, maternal smoking throughout pregnancy remained significantly associated with increased levels of IL-8 (beta = 0.20, 95% confidence interval: 0.07, 0.32; p < .003). No significant associations were found with cigarette load or secondhand smoke exposure. Higher IgG3 levels were also associated with maternal smoking throughout pregnancy, although the association became nominally significant after adjustment for covariates (beta = 0.09; 95% confidence interval: 0.0007, 0.17; p < .05). CONCLUSIONS: Maternal smoking throughout pregnancy was independently associated with increased IL-8 levels in newborns. Importantly, neonates of women who stopped smoking anytime in pregnancy did not have increased IL-8 levels. IMPLICATIONS: This study evaluated a range of inflammatory biomarkers and immunoglobulins in association with maternal smoking and timing/duration of smoking along with secondhand smoke exposure. By using DBSs, we present data from a large cohort of children born in Upstate New York. Our findings suggest that early differences in immunoregulation of neonates exposed to maternal smoking for full duration in utero may already be detected at birth.

BACKGROUND/OBJECTIVES: Maternal obesity may influence neonatal and childhood morbidities through increased inflammation and/or altered immune response. Less is known about paternal obesity. We hypothesized that excessive parental weight contributes to elevated inflammation and altered immunoglobulin (Ig) profiles in neonates. SUBJECTS/METHODS: In the Upstate KIDS Study maternal pre-pregnancy body mass index (BMI) was obtained from vital records and paternal BMI from maternal report. Biomarkers were measured from newborn dried blood spots (DBS) among neonates whose parents provided consent. Inflammatory scores were calculated by assigning one point for each of five pro-inflammatory biomarkers above the median and one point for an anti-inflammatory cytokine below the median. Linear regression models and generalized estimating equations were used to estimate mean differences (beta) and 95% confidence intervals (CI) in the inflammatory score and Ig levels by parental overweight/obesity status compared with normal weight. RESULTS: Among 2974 pregnancies, 51% were complicated by excessive maternal weight (BMI>25), 73% by excessive paternal weight and 28% by excessive gestational weight gain. Maternal BMI categories of overweight (BMI 25.0-29.9) and obese class II/III (BMI>/=35) were associated with increased neonatal inflammation scores (beta=0.12, 95% CI: 0.02, 0.21; P=0.02 and beta=0.13, CI: -0.002, 0.26; P=0.05, respectively) but no increase was observed in the obese class I group (BMI 30-34.9). Mothers with class I and class II/III obesity had newborns with increased IgM levels (beta=0.11, CI: 0.04, 0.17; P=0.001 and beta=0.12, CI: 0.05, 0.19); P<0.001, respectively). Paternal groups of overweight, obese class I and obese class II/III had decreased neonatal IgM levels (beta=-0.08, CI: -0.13,-0.03, P=0.001; beta=-0.07, CI: -0.13, -0.01, P=0.029 and beta=-0.11, CI:-0.19,-0.04, P=0.003, respectively). CONCLUSIONS: Excessive maternal weight was generally associated with increased inflammation and IgM supporting previous observations of maternal obesity and immune dysregulation in offspring. The role of paternal obesity requires further study.

The World Trade Center (WTC) disaster released large amounts of various chemical substances into the environment, including perfluoroalkyl substances (PFASs). Yet, no studies have examined exposures in children living or attending schools near the disaster site. We measured serum PFASs in WTC Health Registry (WTCHR) respondents who were