High plasma IL-6 levels may enhance the adverse effects of mouse allergen exposure in urban schools on asthma morbidity in children.

BACKGROUND: Few data on the relationships between environmental exposures, asthma morbidity, and systemic IL-6 inflammation exist. OBJECTIVE: We sought to determine whether baseline plasma IL-6 level is associated with increased asthma morbidity in children exposed to mouse allergen in inner-city classrooms. METHODS: Data from the longitudinal School Inner-City Asthma Studies of 215 children with asthma, aged 4 to 14 years and recruited from urban elementary schools, were analyzed. Given the unknown threshold of IL-6 risk levels and skewness of the distribution, the children were stratified into tertiles as follows: low baseline IL-6 level (<0.013 pg/mL), moderate baseline IL-6 level (0.013-0.302 pg/mL), and high baseline IL-6 level (>0.302 pg/mL). Relationships between plasma IL-6 level and body mass index (BMI) percentile, inflammatory markers, lung function, mouse allergen exposure, and asthma outcomes were assessed. RESULTS: Cross-sectional analysis demonstrated that increasing IL-6 level was associated with higher BMI percentile (P < .0001), C-reactive protein level (P = .0006), and blood neutrophil count (P = .0024). IL-6 was not associated with type 2 inflammatory markers, including blood eosinophil count, allergic sensitization, or fractional exhaled nitric oxide level. Longitudinal analysis showed that children with high IL-6 levels had a higher number of days with asthma symptoms than did those children with moderate (incidence rate ratio = 1.74 [95% CI = 1.10-2.77]; P = .0187) or low (incidence rate ratio =1.83 [95% CI = 1.21-2.77]; P = .0043) IL-6 levels. Children with high IL-6 levels who were exposed to increasing levels of mouse allergen exhibited lower ratios of FEV1 value to forced vital capacity than did children with moderate IL-6 levels (ß = -0.0044 [95% CI = -0.0073 to -0.0015]; pairwise interaction P = .0028) or low IL-6 levels (ß = -0.0042 [95% CI = - 0.0070 to -0.0013]; pairwise interaction P = .0039). CONCLUSIONS: Inner-city children with asthma and high plasma IL-6 levels are more likely to have an increased BMI, elevated C-reactive protein level, elevated blood neutrophil count, and greater asthma symptoms. High IL-6 level appears to increase susceptibility to the effects of classroom exposure to mouse allergen on lung function in urban children.

Associations of early life urinary triclosan concentrations with maternal, neonatal, and child thyroid hormone levels.

BACKGROUND: Triclosan, an antimicrobial agent used in some consumer products, reduces endogenous thyroid hormone concentrations in rodents. Despite ubiquitous triclosan exposure and the importance of thyroid hormones for normal fetal development, few human studies have examined the impact of triclosan exposure on maternal, neonatal, or child thyroid hormones. METHODS: In the HOME Study, a prospective cohort from Cincinnati, OH, we measured urinary triclosan concentrations up to three times in pregnant women between 16weeks and delivery, and up to three times in children between age 1-3years. We quantified serum concentrations of thyroid stimulating hormone and total and free thyroxine and triiodothyronine in mothers at 16-weeks gestation (n=202), neonates at delivery (n=274), and children at age 3years (n=153). We estimated covariate-adjusted differences in thyroid hormones with a 10-fold increase in triclosan using linear regression and multiple informants models. RESULTS: Triclosan was not associated with thyroid hormones during pregnancy. We observed a few associations of triclosan concentrations with thyroid hormone concentrations in neonates at delivery and children at age 3years. Higher gestational triclosan, particularly around the time of delivery, was associated with lower cord serum total thyroxine (ß: 0.3µg/dL; 95% CI: -0.6, -0.0). Childhood triclosan, particularly at age 1year, was positively associated with total thyroxine at age 3years (ß: 0.7µg/dL; 95% CI: 0.3, 1.2). CONCLUSION: Our findings suggest that triclosan exposure may influence some features of neonatal and early child thyroid function. Given the large number of comparisons we made, these findings should be replicated in other cohorts.

Gestational triclosan exposure and infant birth weight: A systematic review and meta-analysis.

BACKGROUND: Exposure to triclosan, an antimicrobial chemical used in some personal care and cleaning products, has been associated with reduced birth weight in some, but not all epidemiological studies. OBJECTIVES: We conducted a systematic review and meta-analysis to characterize the relation of gestational triclosan exposure with infant birth weight and identify sources of heterogeneity between studies. METHODS: We identified original studies measuring urinary triclosan concentrations during pregnancy and reporting their association with infant birth weight, gestational age (GA) adjusted birth weight (g), or GA-standardized birth weight z-scores. Using a random effects model, we estimated differences in these outcomes per 10-fold increase in triclosan concentrations and considered triclosan levels and infant sex as sources of heterogeneity. Using Navigation Guide Methods, we evaluated risk of bias within individual studies and across the body of evidence. RESULTS: Among thirteen studies, median triclosan concentrations varied by almost 2-orders of magnitude (0.6-29 ng/mL), with higher concentrations in North American and some European studies compared to Asian ones. Associations between triclosan and birth weight (ß:-20 g; 95% CI:-65, 26; n = 6) were stronger than those for GA-adjusted birth weight (ß:-12 g; 95% CI:-29, 5; n = 9). Triclosan was not associated with GA-standardized birth weight z-scores (ß:-0.04; 95% CI:-0.16, 0.07; n = 5). The association between triclosan and GA-adjusted birth weight was stronger in studies with median triclosan values ≥10 ng/mL compared to studies with median values < 10 ng/mL (ß:-27 g; 95% CI:-61, 7; n = 4 vs. ß:6g; 95% CI:-20, 31; n = 5). With a limited number of studies, we observed suggestive evidence that inverse associations were more apparent in studies with ≥ 2 prospective triclosan measures compared to those with one measure. DISCUSSION: Available evidence, with "low" risk of bias, provides limited evidence that triclosan exposure and reduces infant birth weight. We observed stronger inverse associations between triclosan concentrations and birth weight in populations with higher triclosan exposure.

Does fetal leptin and adiponectin influence children's lung function and risk of wheeze?

Adipocytokines, which are secreted during fetal development by both mothers and fetuses, may influence fetal lung development, but little human data are available. We used data from the HOME Study to investigate the associations of cord blood adipocytokine concentrations with children's lung forced expiratory volume (FEV1; N = 160) and their risk of wheeze (N = 281). We measured umbilical cord serum adipocytokine concentrations using enzyme-linked immunosorbent assays and FEV1 using a portable spirometer at ages 4 and 5 to calculate the percent predicted FEV1 (%FEV1). Parents completed standardized questionnaires of their child's wheeze symptoms every 6 months from birth to age 5, then again at ages 6 and 8. We used multivariable linear mixed models and modified Poisson regression with generalized estimating equations to estimate associations of adipocytokine concentrations (log2-transformed) with children's %FEV1 and the risk of wheeze, respectively, adjusting for sociodemographic, perinatal, and child factors. Cord serum leptin was not associated with children's %FEV1. Higher cord serum adiponectin concentrations were associated with higher %FEV1 in girls (ß = 3.1, 95% confidence interval [CI]: 0.6, 5.6), but not in boys (ß = -1.3, 95% CI: -5.9, 3.3) (sex × adiponectin p-value = 0.05). Higher leptin was associated with lower risk of wheeze in girls (RR = 0.74, 95% CI: 0.66, 0.84), but not boys (RR = 0.87, 95% CI: 0.69, 1.11) (sex × leptin p-value = 0.01). In contrast, higher adiponectin concentrations were associated with lower risk of wheeze (RR = 0.84, 95% CI: 0.73, 0.96) in both boys and girls. These data suggest that fetal adipocytokines may impact lung development and function in early childhood. Future studies are needed to confirm these findings and explore the mechanisms underlying these associations.

PFAS (per- and polyfluoroalkyl substances) and asthma in young children: NHANES 2013-2014.

Per- and polyfluoroalkyl substances (PFAS) are a class of persistent chemicals used as industrial surfactants, fire-fighting foams, and textile treatments. Early childhood exposure to perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) may affect the immune system to increase the risk of allergic and respiratory diseases. However, there are substantial gaps in our knowledge about the relationship between PFAS and immune-mediated outcomes such as asthma in children. Thus, we examined the cross-sectional associations of serum PFOA, PFOS, PFNA, and PFHxS concentrations with childhood asthma. We used data from children aged 3-11 years who participated in the National Health and Nutrition Examination Survey (2013-2014). Serum PFAS concentrations were measured in serum using analytical chemistry methods. Asthma was assessed by parent-reported, doctor-diagnosed, asthma using a standardized questionnaire. Controlling for covariates, we estimated odds ratios for asthma per standard deviation increase in ln-transformed serum PFAS concentrations (n = 607). We also examined effect measure modification by child age, sex, and race/ethnicity. PFOA (1.1; 95% CI: 0.8, 1.4), PFOS (1.2; 95% CI: 0.8, 1.7), PFNA (1.1; 95% CI: 0.8, 1.6), and PFHxS (1.1; 95% CI: 0.9, 1.6) were weakly associated with an increased odds of asthma. Age modified associations between serum PFOS, but not other serum PFAS concentrations, and odds of asthma (age x PFOS interaction term p-value = 0.03). Sex and race/ethnicity did not modify these associations. We observed some evidence that serum PFAS concentrations are weakly associated with increased asthma prevalence in US children.

Gestational and childhood urinary triclosan concentrations and academic achievement among 8-year-old children.

BACKGROUND: Early life exposure to triclosan, an antimicrobial chemical and suspected endocrine disruptor, may adversely affect neurodevelopment. No studies have examined gestational and early childhood exposure to triclosan and children's academic achievement. METHODS: Using data from 193 mother-child pairs from the HOME Study, we quantified triclosan in maternal and child urine samples up to nine times between the second trimester of gestation (16-weeks) and age 8 years. At age 8 years, we administered the reading and math components of the Wide Range Achievement Test-4 (WRAT-4) to children. Using multiple informants models, we estimated covariate-adjusted associations of triclosan concentrations during each time period with WRAT-4 scores. We also tested whether associations differed by exposure period and child sex. RESULTS: There was evidence that timing of exposure modified the associations between triclosan and reading composite scores (triclosan-exposure period interaction p-value = 0.20), but not math scores (interaction p-value = 0.72). Each 10-fold increase in triclosan concentrations at delivery was associated with lower reading composite scores (ß:-2.6; 95 % CI:-5.0, -0.1). Additionally, we observed weaker and less precise inverse association of math scores with triclosan concentrations at delivery (ß:-1.9; 95 % CI:-4.6, 0.8) and at age 1 year (ß:-2.0; 95 % CI:-6.0, 2.1). There was not strong evidence that child sex modified the pattern of associations between repeated triclosan measures and WRAT-4 reading composite or math scores (sex-triclosan-exposure period interaction p-values>0.20). CONCLUSION: Urinary triclosan concentrations at delivery and at age 1 year, but not other times during gestation or childhood, were associated with lower reading composite and to a lesser extent math test scores at age 8 years in this cohort of U.S. children.

The Impact of Early-Life Exposure to Antimicrobials on Asthma and Eczema Risk in Children.

PURPOSE OF REVIEW: We examined recent research on associations of prenatal and early-childhood exposure to the antimicrobial compounds, triclosan, and parabens, with the risk of asthma and eczema in children. We will discuss potential biological mechanisms of this association and highlight strengths and limitations of the study design and exposure assessment of current findings. RECENT FINDINGS: Results of available toxicological and epidemiologic studies indicate a potential link of triclosan and paraben exposures with asthma and eczema in children, as well as changes in microbiome diversity and immune dysfunction, which could possibly mediate an association with the health outcomes. A small number of studies suggest that triclosan and paraben exposures could be related to the risk of asthma and eczema in children. Although current findings are far from conclusive, there is emerging evidence that changes in microbiome diversity and immune function from antimicrobial exposure may mediate these relations.

Early-life triclosan exposure and parent-reported behavior problems in 8-year-old children.

BACKGROUND: Triclosan exposure may decrease circulating thyroxine levels or cause neuron apoptosis, which in turn may adversely affect neurodevelopment. However, few studies have examined the association of early life triclosan exposure with child behavior. OBJECTIVE: To quantify the association between early-life triclosan exposure and child behavior at age 8-years in 202 mother-child pairs from the HOME study (Cincinnati, OH; enrolled: 2003-2006). METHODS: We quantified urinary triclosan concentrations up to 3 times in mothers (16-weeks, 26-weeks, and delivery) and up to 6 times in children (1, 2, 3, 4, 5, and 8 years). Parents rated children's problem behaviors at age 8-years using the Behavioral Assessment System for Children-2 (BASC-2). Adjusting for covariates and accounting for exposure measurement error, we estimated changes in behavior problem scores per 10-fold increase in mean gestational and childhood triclosan concentrations. In addition, we estimated sex-specific associations. RESULTS: Child sex modified the association of gestational and childhood triclosan with several BASC-2 scales (sex × triclosan p-values < 0.2). In boys, increasing gestational triclosan was associated with higher behavioral symptom index (ß: 4.5; 95% CI: 1.0, 8.1), externalizing problems (ß: 5.0; 95% CI: 1.2, 9.0), attention problem (ß: 6.6; 95% CI: 2.4, 11), hyperactivity (ß: 6.4; 95% CI: 2.1, 11), and somatization (ß: 3.8; 95% CI: 0.3, 7.3) scores. In contrast, triclosan-BASC-2 associations in girls were generally null and not statistically significant. We observed similar patterns of associations between childhood triclosan and these same behavioral scores; however, their magnitude decreased substantially after adjusting for gestational triclosan and associations were not statistically significant. CONCLUSION: In this cohort, increasing gestational and childhood urinary triclosan concentrations were associated with higher behavior problem scores in 8-year old boys, but not girls.

Identifying Vulnerable Periods of Neurotoxicity to Triclosan Exposure in Children.

BACKGROUND: Exposure to triclosan, an endocrine disrupting chemical, may affect thyroid hormone homeostasis and adversely affect neurodevelopment. OBJECTIVE: Using a longitudinal pregnancy and birth cohort, we investigated associations between triclosan exposures during different time windows, and cognitive test scores at 8 y of age in 198 children from the HOME Study. METHODS: We quantified triclosan in urine samples from mother-child pairs up to nine times between the second trimester of gestation and 8 y of age. The Wechsler Intelligence Scale for Children-IV [i.e., Full-Scale Intelligence Quotient (IQ)] assessment was administered to HOME Study children at 8 y of age. We estimated covariate-adjusted triclosan-IQ associations at each visit. We also tested whether associations between triclosan concentrations and cognitive test scores varied among exposure at different time periods. RESULTS: Full-Scale IQ was not significantly associated with urinary triclosan concentrations during gestation or childhood but was significantly associated with a 10-fold increase in maternal urinary triclosan concentration at delivery [-4.5 points (95% CI: -7.0, -2.0)]. Perceptual Reasoning Index (PRI) scores were significantly decreased in association with urinary triclosan concentrations at delivery and at 2 y of age. Associations between repeated triclosan concentrations and cognitive test scores significantly varied among exposure at different time periods for Full-Scale IQ, PRI, Verbal Comprehension Index, and Working Memory (triclosan-visit interaction p≤0.04). CONCLUSION: Urinary triclosan concentrations at delivery, but not during mid to late pregnancy and childhood, were associated with significantly lower children's cognitive test scores at 8 y of age in this cohort of U.S. children. https://doi.org/10.1289/EHP2777.

Web-based Real-Time Case Finding for the Population Health Management of Patients With Diabetes Mellitus: A Prospective Validation of the Natural Language Processing-Based Algorithm With Statewide Electronic Medical Records.

BACKGROUND: Diabetes case finding based on structured medical records does not fully identify diabetic patients whose medical histories related to diabetes are available in the form of free text. Manual chart reviews have been used but involve high labor costs and long latency. OBJECTIVE: This study developed and tested a Web-based diabetes case finding algorithm using both structured and unstructured electronic medical records (EMRs). METHODS: This study was based on the health information exchange (HIE) EMR database that covers almost all health facilities in the state of Maine, United States. Using narrative clinical notes, a Web-based natural language processing (NLP) case finding algorithm was retrospectively (July 1, 2012, to June 30, 2013) developed with a random subset of HIE-associated facilities, which was then blind tested with the remaining facilities. The NLP-based algorithm was subsequently integrated into the HIE database and validated prospectively (July 1, 2013, to June 30, 2014). RESULTS: Of the 935,891 patients in the prospective cohort, 64,168 diabetes cases were identified using diagnosis codes alone. Our NLP-based case finding algorithm prospectively found an additional 5756 uncodified cases (5756/64,168, 8.97% increase) with a positive predictive value of .90. Of the 21,720 diabetic patients identified by both methods, 6616 patients (6616/21,720, 30.46%) were identified by the NLP-based algorithm before a diabetes diagnosis was noted in the structured EMR (mean time difference = 48 days). CONCLUSIONS: The online NLP algorithm was effective in identifying uncodified diabetes cases in real time, leading to a significant improvement in diabetes case finding. The successful integration of the NLP-based case finding algorithm into the Maine HIE database indicates a strong potential for application of this novel method to achieve a more complete ascertainment of diagnoses of diabetes mellitus.