This article discusses critical issues and opportunities going forward in nanotechnology environmental, health, and safety (nanoEHS) research from the perspective of Federal Government Agency participants in the United States (U.S.) National Nanotechnology Initiative (NNI) interagency Nanotechnology Environmental and Health Implications Working Group (NEHI). NEHI is responsible for coordination of Federal Science Agency nanoEHS research. As participants in NEHI, we examine these critical issues from an integrated, transdisciplinary perspective, noting examples of impactful research efforts that are advancing knowledge in these areas. Major themes identified include detection, measurement, and characterization of real-world nanomaterial exposures, understanding the biological transformation of nanomaterials and their potential (eco) toxicological implications, understanding the landscape of nanotechnology-enabled products in commerce, and advancing the EHS knowledge infrastructure related to nanomaterials and nanotechnology. Significant investments in nanoEHS research over two decades have led to establishment of a unique and diverse multidisciplinary, multisector community of practice. These investments must be leveraged and adapted not only to future nanotechnology, but also to use as a model for accelerating acquisition of safe and reliable risk information for tomorrow's emerging technologies for a more sustainable and competitive world. © 2023 The Royal Society of Chemistry.

BACKGROUND: Fetal alcohol syndrome (FAS) typically is observed among individuals with high prenatal alcohol exposures (PAE), but exposure histories obtained in clinical diagnostic settings are often inaccurate. The present analysis used the Lifestyle During Pregnancy Study (LDPS) to assess the potential effects of low to moderate average weekly alcohol consumption and binge drinking in early pregnancy on facial features associated with FAS among children five years of age. METHODS: The analysis is a prospective follow-up study of 670 women and their children sampled from the LDPS cohort based on maternal alcohol consumption during pregnancy. The 4-Digit Code FAS Facial Photographic software was used to measure the magnitude of expression of the three diagnostic facial features of FAS from standardized digital photographs. Logistic regression was used to estimate the odds of presenting with the FAS/Partial FAS (PFAS) facial phenotypes relative to different patterns of prenatal alcohol exposure. RESULTS: Ten children presented with the FAS/PFAS facial phenotypes. None of the children sampled met the central nervous system (CNS) criteria for FAS or PFAS at age 5 years. All remained at risk for PFAS since some types of CNS dysfunction associated with this diagnosis may only be assessed at older ages. The FAS/PFAS facial phenotypes were 8.5-fold more likely among children exposed to an average of 1-4 drinks per week, and 2.5-fold more likely among children with a single binge exposure in gestational weeks 3-4 compared to children with no such exposures. The magnitude of expression of the FAS facial phenotype was significantly correlated with all other diagnostic features of FAS: growth deficiency, microcephaly, and measures of CNS dysfunction. CONCLUSIONS: These findings suggest that low to moderate levels of PAE or isolated binge exposures may place some fetuses at risk for FAS/PFAS. Thus, conservative advice is still for women to abstain from alcohol consumption during pregnancy. This article is protected by copyright. All rights reserved.

In 2012, the Centers for Disease Control and Prevention (CDC) adopted its Advisory Committee on Childhood Lead Poisoning Prevention recommendation to use a population-based reference value to identify children and environments associated with lead hazards. The current reference value of 5 mug/dL is calculated as the 97.5th percentile of the distribution of blood lead levels (BLLs) in children 1 to 5 years old from 2007 to 2010 NHANES data. We calculated and updated selected percentiles, including the 97.5th percentile, by using NHANES 2011 to 2014 blood lead data and examined demographic characteristics of children whose blood lead was ≥90th percentile value. The 97.5th percentile BLL of 3.48 microg/dL highlighted analytical laboratory and clinical interpretation challenges of blood lead measurements ≤5 mug/dL. Review of 5 years of results for target blood lead values <11 microg/dL for US clinical laboratories participating in the CDC's voluntary Lead and Multi-Element Proficiency quality assurance program showed 40% unable to quantify and reported a nondetectable result at a target blood lead value of 1.48 microg/dL, compared with 5.5% at a target BLL of 4.60 microg/dL. We describe actions taken at the CDC's Environmental Health Laboratory in the National Center for Environmental Health, which measures blood lead for NHANES, to improve analytical accuracy and precision and to reduce external lead contamination during blood collection and analysis.

BACKGROUND: There have been increasing concerns over health effects of low level exposure to cadmium, especially those on bones and kidneys. OBJECTIVE: To explore how age-adjusted geometric means of blood cadmium in adults varied by race/Hispanic origin, sex, and smoking status among U.S. adults and the extent to which the difference in blood cadmium by race/Hispanic origin and sex may be explained by intensity of smoking, a known major source of cadmium exposure. METHODS: Our sample included 7,368 adults from National Health and Nutrition Examination Survey (NHANES) 2011-2014. With direct age adjustment, geometric means of blood cadmium and number of cigarettes smoked per day were estimated for subgroups defined by race/Hispanic origin, smoking status, and sex using interval regression, which allows mean estimation in the presence of left- and right-censoring. RESULTS: Among never and former smoking men and women, blood cadmium tended to be higher for non-Hispanic Asian adults than adults of other race/Hispanic origin. Among current smokers, who generally had higher blood cadmium than never and former smokers, non-Hispanic white, black, and Asian adults had similarly elevated blood cadmium compared to Hispanic adults. A separate analysis revealed that non-Hispanic white adults tended to have the highest smoking intensity regardless of sex, than adults of the other race/Hispanic origin groups. CONCLUSIONS: The observed pattern provided evidence for smoking as a major source of cadmium exposure, yet factors other than smoking also appeared to contribute to higher blood cadmium of non-Hispanic Asian adults.

BACKGROUND: General population human biomonitoring programs such as the National Health and Nutrition Examination Survey (NHANES) in the United States suggest that chemical exposures are common. Exposures during childhood may affect health later in life, but biomonitoring data in NHANES among pre-school aged children are limited. METHODS: A convenience group of 122 3-5year old American boys and girls were recruited in 2013 for a pilot study to assess the feasibility of collecting urine from young children and analyzing it for select chemical exposure biomarkers for future NHANES. Children were primarily Hispanic (64.8%); the remainder was divided between non-Hispanic black, and non-Hispanic white and "other." We measured 52 urinary biomarkers: 13 phthalates and one non-phthalate plasticizer, five phenols and four parabens, 10 polycyclic aromatic hydrocarbons (PAHs), and 19 pesticides. For each biomarker, we calculated descriptive statistics. We also calculated the number of biomarkers detected within each child, and performed principal components analysis (PCA). RESULTS: NHANES staff obtained permission to attempt collection of 60mL urine from 3 to 5year olds who participated in the 2013 NHANES health examination; 83% of children successfully provided the target volume. We detected 24 individual biomarkers of pesticides, phenols and parabens, phthalates/non-phthalate plasticizers, and PAHs in 95-100% of children. The median number of biomarkers detected was 37: nine pesticides, five phenols and parabens, 13 phthalates and non-phthalate plasticizers, and 10 PAHs. Biomarkers concentrations appear to be similar to national estimates among 6-11year old children from previous NHANES. PCA suggested high within-class correlations among biomarkers. CONCLUSIONS: These young children successfully adhered to the collection protocol and produced enough urine for the quantification of environmental biomarkers currently being measured in NHANES participants 6 years of age and older. Using the same analytical methods employed for the analysis of samples collected from older NHANES participants, in this sample of pre-school aged children we detected multiple chemicals including plasticizers, combustion products, personal-care product chemicals, and pesticides. Starting with NHANES 2015-2016, the NHANES biomonitoring program will include urinary biomarkers for 3-5year old children to provide exposure data to select chemicals at the national level among this age group.

The sodium iodide-symporter (NIS) mediates uptake of iodide into thyroid follicular cells. This key step in thyroid hormone synthesis is inhibited by perchlorate, thiocyanate (SCN) and nitrate (NO3) anions. When these exposures occur during pregnancy the resulting decreases in thyroid hormones may adversely affect neurodevelopment of the human fetus. Our objectives were to describe and examine the relationship of these anions to the serum thyroid indicators, thyroid stimulating hormone (TSH) and free thyroxine (FT4), in third trimester women from the initial Vanguard Study of the National Children's Study (NCS); and to compare urine perchlorate results with those in pregnant women from the National Health and Nutritional Examination Survey (NHANES). Urinary perchlorate, SCN, NO3, and iodine, serum TSH, FT4, and cotinine were measured and a food frequency questionnaire (FFQ) was administered to pregnant women enrolled in the initial Vanguard Study. We used multiple regression models of FT4 and TSH that included perchlorate equivalent concentration (PEC, which estimates combined inhibitory effects of the anions perchlorate, SCN, and NO3 on the NIS). We used multiple regression to model predictors of each urinary anion, using FFQ results, drinking water source, season of year, smoking status, and demographic characteristics. Descriptive statistics were calculated for pregnant women in NHANES 2001-2012. The geometric mean (GM) for urinary perchlorate was 4.04microg/L, for TSH 1.46mIU/L, and the arithmetic mean for FT4 1.11ng/dL in 359 NCS women. In 330 women with completed FFQs, consumption of leafy greens, winter season, and Hispanic ethnicity were significant predictors of higher urinary perchlorate, which differed significantly by study site and primary drinking water source, and bottled water was associated with higher urinary perchlorate compared to filtered tap water. Leafy greens consumption was associated with higher urinary NO3 and higher urinary SCN. There was no association between urinary perchlorate or PEC and TSH or FT4, even for women with urinary iodine <100microg/L. GM urinary perchlorate concentrations in the full sample (n=494) of third trimester NCS women (4.03microg/L) were similar to pregnant women in NHANES (3.58microg/L).

Epidemiologic studies can measure exposure to volatile organic compounds (VOCs) using environmental samples, biomarkers, questionnaires, or observations. These different exposure assessment approaches each have advantages and disadvantages; thus, evaluating relationships is an important consideration. In the National Children's Vanguard Study from 2009 to 2010, participants completed questionnaires and data collectors observed VOC exposure sources and collected urine samples from 488 third trimester pregnant women at in-person study visits. From urine, we simultaneously quantified 28 VOC metabolites of exposure to acrolein, acrylamide, acrylonitrile, benzene, 1-bromopropane, 1,3-butadiene, carbon disulfide, crotonaldehyde, cyanide, N,N-dimethylformamide, ethylbenzene, ethylene oxide, propylene oxide, styrene, tetrachloroethylene, toluene, trichloroethylene, vinyl chloride, and xylene exposures using ultra high performance liquid chromatography coupled with an electrospray ionization tandem mass spectrometry (UPLC-ESI/MSMS) method. Urinary thiocyanate was measured using an ion chromatography coupled with an electrospray ionization tandem mass spectrometry method (IC-ESI/MSMS). We modeled the relationship between urinary VOC metabolite concentrations and sources of VOC exposure. Sources of exposure were assessed by participant report via questionnaire (use of air fresheners, aerosols, paint or varnish, organic solvents, and passive/active smoking) and by observations by a trained data collector (presence of scented products in homes). We found several significant (p < 0.01) relationships between the urinary metabolites of VOCs and sources of VOC exposure. Smoking was positively associated with metabolites of the tobacco constituents acrolein, acrylamide, acrylonitrile, 1,3-butadiene, crotonaldehyde, cyanide, ethylene oxide, N,N-dimethylformamide, propylene oxide, styrene, and xylene. Study location was negatively associated with the toluene metabolite N-acetyl-S-(benzyl)-l-cysteine (BMA), and paint use was positively associated with the xylene metabolites 2-methylhippuric acid (2MHA) and 3-Methylhippuric acid &amp; 4-methylhippuric acid (3MHA + 4MHA). A near-significant (p = 0.06) relationship was observed between acrylamide metabolites and observation of incense.

This study examined the effects of maternal alcohol consumption and binge drinking during pregnancy on children's Draw-A-Person (DAP) scores. Participants were 1,533 5-year-olds from the Danish National Birth Cohort. Regression analyses revealed an adverse effect of nine or more drinks per week. A drop in mean DAP score of 6.26 (95 % CI: -12.24; -0.39) was observed in the fully adjusted model. A significant interaction between average weekly consumption and binge episodes also was observed. Findings suggest that prenatal exposure to moderate weekly doses of alcohol and binge drinking episodes are associated with lowered scores on the DAP.

OBJECTIVE: To examine the effects of pre-pregnancy alcohol drinking on child neuropsychological functioning. DESIGN: Prospective follow-up study. SETTING AND POPULATION: 154 women and their children sampled from the Danish National Birth Cohort. METHODS: Participants were sampled based on maternal alcohol consumption before pregnancy. At 5 years of age, the children were tested with the Wechsler Preschool and Primary Scale of Intelligence-Revised, the Test of Everyday Attention for Children at Five (TEACh-5), and the Movement Assessment Battery for Children (MABC). The Behaviour Rating Inventory of Executive Function (BRIEF) was completed by the mothers and a preschool teacher. Parental education, maternal IQ, prenatal maternal smoking, child's age at testing, child's sex, and maternal alcohol intake during pregnancy were considered potential confounders. MAIN OUTCOME MEASURES: Performance on the Wechsler Preschool and Primary Scale of Intelligence-Revised, the TEACh-5, the MABC, and the BRIEF. RESULTS: Intake of 15-21 drinks/week on average prior to pregnancy was not associated with any of the outcomes, but intake of ≥22 drinks/week on average was associated with a significantly lower adjusted mean full scale IQ and lower adjusted means in overall attention and sustained attention score, but not in selective attention score or any of the BRIEF index scores or MABC scores. CONCLUSIONS: Intake of ≥22 drinks/week before pregnancy was associated with lower mean full scale IQ, overall attention and sustained attention. Assessment of pre-pregnancy drinking provides additional information regarding potential prenatal alcohol exposure and its implications for child neurodevelopment.

BACKGROUND: Human exposure to the widespread environmental contaminant mercury is a known risk factor for common diseases such as cancer, cardiovascular disease and neurological disorders through poorly characterized mechanisms. Evidence suggests mercury exposure may alter DNA methylation levels, but to date, the effects in early life on a genome-wide scale have not been investigated. METHODS: A study sample of 141 newborns was recruited in Baltimore, MD, USA and total mercury and methylmercury were measured in cord blood samples. We quantified genome-wide DNA methylation data using CHARM 2.0, an array-based method, and used region-finding analyses to identify concentration-associated differentially methylated regions (DMRs). To test for replication of these identified DMRs in the pilot, or Vanguard, phase of the National Children's Study (NCS), we compared bisulfite-pyrosequenced DNA at candidate regions from 85 whole cord blood samples with matched first trimester maternal mercury concentration measures. RESULTS: Total mercury concentration was associated with methylation at DMRs inside ANGPT2 and near PRPF18 genes [false discovery rate (FDR) < 0.05], as well as DMRs near FOXD2 and within TCEANC2 (FDR< 0.1) genes. Methylmercury concentration was associated with an overlapping DMR within TCEANC2 (FDR< 0.05). In NCS replication analyses, methylation levels at three of four cytosine-guanine DNA dinucleotides (CpG sites) within the TCEANC2 DMR were associated with total mercury concentration (P < 0.05), and this association was diminished after adjusting for estimated cell proportions. CONCLUSIONS: Evidence for an association between mercury and DNA methylation at the TCEANC2 region was found, which may represent a mercury-associated shift in cord blood cell composition or a change in methylation within blood cell types. Further confirmatory studies are needed.

BACKGROUND: Arsenic is an ubiquitous element linked to carcinogenicity, neurotoxicity, as well as adverse respiratory, gastrointestinal, hepatic, and dermal health effects. OBJECTIVE: Identify dietary sources of speciated arsenic: monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA). METHODS: Age-stratified, sample-weighted regression of NHANES (National Health and Nutrition Examination Survey) 2003-2010 data ( approximately 8,300 participants ≥6 years old) characterized the association between urinary arsenic species and the additional mass consumed of USDA-standardized food groups (24-hour dietary recall data), controlling for potential confounders. RESULTS: For all arsenic species, the rank-order of age strata for median urinary molar concentration was children 6-11 years > adults 20-84 years > adolescents 12-19 years, and for all age strata, the rank-order was DMA > MMA. Median urinary molar concentrations of methylated arsenic species ranged from 0.56 to 3.52 micromol/mol creatinine. Statistically significant increases in urinary arsenic species were associated with increased consumption of: fish (DMA); fruits (DMA, MMA); grain products (DMA, MMA); legumes, nuts, seeds (DMA); meat, poultry (DMA); rice (DMA, MMA); rice cakes/crackers (DMA, MMA); and sugars, sweets, beverages (MMA). And, for adults, rice beverage/milk (DMA, MMA). In addition, based on US (United States) median and 90th percentile consumption rates of each food group, exposure from the following food groups was highlighted: fish; fruits; grain products; legumes, nuts, seeds; meat, poultry; and sugars, sweets, beverages. CONCLUSIONS: In a nationally representative sample of the US civilian, noninstitutionalized population, fish (adults), rice (children), and rice cakes/crackers (adolescents) had the largest associations with urinary DMA. For MMA, rice beverage/milk (adults) and rice cakes/crackers (children, adolescents) had the largest associations.

BACKGROUND: Despite the public health and toxicologic interest in methyl mercury (MeHg) and ethyl mercury (EHg), these mercury species have been technically difficult to measure in large population studies. METHODS: Using NHANES 2011-2012 data, we calculated reference ranges and examined demographic factors associated with specific mercury species concentrations and the ratio of MeHg to THg. We conducted several multiple regression analyses to examine factors associated with MeHg concentrations and also with the ratio of MeHg to THg. RESULTS: Asians had the highest geometric mean concentrations for MeHg, 1.58microg/L (95% CI 1.29, 1.93) and THg, 1.86microg/L (1.58, 2.19), followed by non-Hispanic blacks with MeHg, 0.52microg/L (0.39, 0.68) and THg, 0.68microg/L (0.54, 0.85). Greater education attainment in adults and male sex were associated with higher MeHg and THg concentrations. Race/ethnicity, age, and sex were significant predictors of MeHg concentrations, which increased with age and were highest in Asians in all age categories, followed by non-Hispanic blacks. Mexican Americans had the lowest adjusted MeHg concentrations. The ratio of MeHg to THg was highest in Asians, varied by racial/ethnic group, and increased with age in a non-linear fashion. The amount of increase in the MeHg to THg ratio with age depended on the initial ratio, with a greater increase as age increased. Of the overall population, 3.05% (95% CI 1.77, 4.87) had MeHg concentrations >5.8microg/L (a value that corresponds to the U.S. EPA reference dose). The prevalence was highest in Asians at 15.85% (95% CI 11.85, 20.56), increased with age, reaching a maximum of 9.26% (3.03, 20.42) at ages 60-69 years. Females 16-44 years old had a 1.76% (0.82-3.28) prevalence of MeHg concentrations >5.8microg/L. CONCLUSIONS: Asians, males, older individuals, and adults with greater educational attainment had higher MeHg concentrations. The ratio of MeHg to THg varied with racial/ethnic group, increased with age, and was nonlinear. U.S. population reference values for MeHg and the ratio of MeHg to THg can assist in more precise assessment of public health risk from MeHg consumed in seafood.

OBJECTIVE: To investigate Acinetobacter baumannii infection, colonization, and transmission related to a long-term care facility (LTCF) providing subacute care (facility A). METHODS: We reviewed facility A and affiliated local hospital records for facility A residents with A. baumannii isolated during the period January 2009 through February 2010 and compared A. baumannii antimicrobial resistance patterns of residents with those of hospital patients. During March 2010, we implemented a colonization survey of facility A residents who received respiratory support or who could provide sputum samples and looked for A. baumannii colonization risks. Available clinical and survey isolates underwent pulsed-field gel electrophoresis (PFGE); PFGE strains were linked with overlapping stays to identify possible transmission. RESULTS: During the period January 2009 through February 2010, 33 facility A residents had A. baumannii isolates; all strains were multidrug resistant (MDR), which was a significantly higher prevalence of MDR strains than that found among isolates from hospital patients (81 [66%] of 122 hospital patient isolates were MDR; P < .001). The sputum survey found that 14 (20%) of 70 residents had A. baumannii colonization, which was associated with ventilator use (adjusted odds ratio, 4.24 [95% confidence interval, 1.06-16.93]); 12 (86%) of 14 isolates were MDR. Four facility A resident groups clustered with 3 PFGE strains and overlapping stays. One of these facility A residents also clustered with 3 patients at an affiliated hospital. CONCLUSIONS: We documented substantial MDR A. baumannii infections and colonization with probable intra- and interfacility spread associated with a single LTCF providing subacute care. Given the limited infection prevention and antimicrobial stewardship resources in such settings, regional collaborations among facilities across the spectrum of health care are needed to address this MDR threat.

Arsenic, cadmium, lead, and mercury present potential health risks to children who are exposed through inhalation or ingestion. Emerging Market countries experience rapid industrial development that may coincide with the increased release of these metals into the environment. A literature review was conducted for English language articles from the 21st century on pediatric exposures to arsenic, cadmium, lead, and mercury in the International Monetary Fund's (IMF) top 10 Emerging Market countries: Brazil, China, India, Indonesia, Mexico, Poland, Russia, South Korea, Taiwan, and Turkey. Seventy-six peer-reviewed, published studies on pediatric exposure to metals met the inclusion criteria. The reported concentrations of metals in blood and urine from these studies were generally higher than US reference values, and many studies identified adverse health effects associated with metals exposure. Evidence of exposure to metals in the pediatric population of these Emerging Market countries demonstrates a need for interventions to reduce exposure and efforts to establish country-specific reference values through surveillance or biomonitoring. The findings from review of these 10 countries also suggest the need for country-specific public health policies and clinician education in Emerging Markets.

Environmental phenols are a group of chemicals with widespread uses in consumer and personal care products, food and beverage processing, and in pesticides. We assessed exposure to benzophenone-3, bisphenol A (BPA), triclosan, methyl- and propyl parabens, and 2,4- and 2,5-dichlorophenol or their precursors in 506 pregnant women enrolled in the National Children's Study (NCS) Vanguard Study. We measured the urinary concentrations of the target phenols by using online solid-phase extraction-isotope dilution high performance liquid chromatography-tandem mass spectrometry. NCS women results were compared to those of 524 similar-aged women in the National Health and Nutrition Examination Survey (NHANES) 2009-2010, and to 174 pregnant women in NHANES 2005-2010. In the NCS women, we found significant racial/ethnic differences (p<0.05) in regression adjusted mean concentrations of benzophenone-3, triclosan, 2,4- and 2,5-dichlorophenol, but not of BPA. Urinary 2,4- and 2,5-dichlorophenol concentrations were highly correlated (r=0.66, p<0.0001). Except for BPA and triclosan, adjusted mean concentrations were significantly different across the 7 study sites. Education was marginally significant for benzophenone-3, triclosan, propyl paraben, and 2,5-dichlorophenol. Urinary concentrations of target phenols in NCS pregnant women and U.S. women and pregnant women were similar. In NCS pregnant women, race/ethnicity and geographic location determined urinary concentrations of most phenols (except BPA), suggesting differential exposures. NCS Main Study protocols should collect urine biospecimens and information about exposures to environmental phenols.

INTRODUCTION: Solid organ transplant recipients have a higher frequency of tuberculosis (TB) than the general population, with mortality rates of approximately 30%. Although donor-derived TB is reported to account for <5% of TB in solid organ transplants, the source of Mycobacterium tuberculosis infection is infrequently determined. METHODS: We report 3 new cases of pulmonary TB in lung transplant recipients attributed to donor infection, and review the 12 previously reported cases to assess whether cases could have been prevented and whether any cases that might occur in the future could be detected and investigated more quickly. Specifically, we evaluate whether opportunities existed to determine TB risk on the basis of routine donor history, to expedite diagnosis through routine mycobacterial smears and cultures of respiratory specimens early post transplant, and to utilize molecular tools to investigate infection sources epidemiologically. FINDINGS: On review, donor TB risk was present among 7 cases. Routine smears and cultures diagnosed 4 asymptomatic cases. Genotyping was used to support epidemiologic findings in 6 cases. CONCLUSION: Validated screening protocols, including microbiological testing and newer technologies (e.g., interferon-gamma release assays) to identify unrecognized M. tuberculosis infection in deceased donors, are warranted.

OBJECTIVE: To examine the effects of low to moderate maternal alcohol consumption and binge drinking in early pregnancy on behaviour in children at the age of 5 years. DESIGN: Prospective cohort study. SETTING: Neuropsychological testing in four Danish cities, 2003-2008. POPULATION: A total of 1628 women and their children sampled from the Danish National Birth Cohort. METHODS: Participants were sampled based on maternal alcohol drinking patterns during early pregnancy. When the children were 5 years of age the parent and teacher versions of the Strengths and Difficulties Questionnaire (SDQ) were completed by the mothers and a preschool teacher, respectively. The full statistical model included the following potential confounding factors: maternal binge drinking or low to moderate alcohol consumption, respectively; parental education; maternal IQ; prenatal maternal smoking; the child's age at testing; the child's gender; maternal age; parity; maternal marital status; family home environment; postnatal parental smoking; prepregnancy maternal body mass index (BMI); and the child's health status. MAIN OUTCOME MEASURE: Behaviour among children assessed by the SDQ parent and teacher forms. RESULTS: Adjusted for all potential confounding factors, no statistically significant associations were observed between maternal low to moderate average weekly alcohol consumption and SDQ behavioural scores (OR 1.1, 95% CI 0.5-2.3; OR 1.1, 95% CI 0.6-2.1 for the total difficulties scores) or between binge drinking and SDQ behavioural scores (OR 1.2, 95% CI 0.8-1.7; OR 0.8, 95% CI 0.6-1.2). CONCLUSION: This study observed no consistent effects of low to moderate alcohol consumption or binge drinking in early pregnancy on offspring behaviour at the age of 5 years.

BACKGROUND: Asthma was the most common chronic condition among adults hospitalized for 2009 pandemic influenza A (H1N1) (pH1N1). OBJECTIVES: We describe the epidemiology and factors for severe outcomes among adults with asthma who were hospitalized or died from pH1N1 in California. METHODS: We reviewed California Department of Public Health pH1N1 reports from April 23, 2009 through August 11, 2009. Reports were included if the patient had pH1N1 (or non-subtypeable influenza A) infection by polymerase chain reaction in an adult (age ≥ 18 years) with asthma who was hospitalized or died. Patients were classified as having intermittent or persistent asthma on the basis of regular medications. Risk factors associated with severe outcomes (i.e., intensive care unit admission or death) vs those with less severe outcomes were assessed by chi-square tests and logistic regression. RESULTS: Among 744 identified patients, 170 (23%) had asthma (61% intermittent, 39% persistent). 132 of 142 (93%) patients had other chronic medical conditions. Severe outcomes occurred in 54 of 162 (33%), more commonly among those with renal disease (64% versus 31%; P = 0.04) and chest radiograph infiltrates (54% versus 11%; P < 0.01), less commonly among those who received antivirals within 48 hours of symptom onset (22% versus 44%; P = 0.02). In multivariable analysis, chest radiograph infiltrates were associated with severe outcomes (adjusted odds ratio 9.38, 95% confidence interval 3.05-28.90). CONCLUSIONS: One third of adults with asthma who died or were hospitalized with pH1N1 experienced severe outcomes. Early empiric antiviral therapy should be encouraged, especially among asthma patients.

BACKGROUND: This report presents iodine data from NHANES and from a sample of pregnant women in the National Children's Study (NCS) Vanguard Study. METHODS: UI was measured in a one third subsample of NHANES 2005-2006, and 2009-2010 participants and in all 2007-2008 participants age six years and older. These measurements are representative of the general U.S. population. UI was also measured in a convenience sample of 501 pregnant women enrolled in the NCS initial Vanguard Study from seven study sites across the U.S. RESULTS: NHANES median UI concentration in 2009-2010 (144 microg/L) was significantly lower than in 2007-2008 (164 microg/L). Non-Hispanic blacks had the lowest UI concentrations (131microg/L) compared to non-Hispanic whites or Hispanics (147 and 148 microg/L, respectively). The median for all pregnant women in NHANES 2005-2010 was less than adequate (129 microg/L), the third trimester women had UI concentrations that were adequate ( median UI 172 microg/L). Third trimester women participating in the NCS study similarly had an adequate level of iodine intake, with a median UI concentration of 167microg/L. Furthermore, NCS median UI concentrations varied by geographic location. CONCLUSIONS: Dairy, but not salt, seafood or grain consumption, was significantly positively associated with median UI concentration in women of childbearing age. Pregnant women in their third trimester in the NHANES 2005-2010 had adequate median UI concentrations, but pregnant women in NHANES who were in their first or second trimesters had median UI concentrations that were less than adequate. Non-Hispanic black pregnant women from both the NHANES 2005-20010 and the NCS consistently had lower UI median concentrations than non-Hispanic whites or Hispanics.

OBJECTIVE: To conduct a combined analysis of the estimated effects of maternal average weekly alcohol consumption, and any binge drinking, in early to mid pregnancy on general intelligence, attention, and executive function in 5-year-old children. DESIGN: Follow-up study. SETTING: Neuropsychological testing in four Danish cities 2003-2008. POPULATION: A cohort of 1628 women and their children sampled from the Danish National Birth Cohort. METHODS: Participants were sampled based on maternal alcohol consumption during early pregnancy. At age 5 years, the children were tested for general intelligence, attention, and executive function. The three outcomes were analysed together in a multivariate model to obtain joint estimates and P values for the association of alcohol across outcomes. The effects of low to moderate alcohol consumption and binge drinking in early pregnancy were adjusted for a wide range of potential confounding factors. MAIN OUTCOME MEASURES: Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), the Test of Everyday Attention for Children at Five (TEACh-5), and the Behavior Rating Inventory of Executive Functions (BRIEF) scores. Results Multivariate analyses showed no statistically significant effects arising from average weekly alcohol consumption or any binge drinking, either individually or in combination. These results replicate findings from separate analyses of each outcome variable. CONCLUSIONS: The present study contributes comprehensive methodological and statistical approaches that should be incorporated in future studies of low to moderate alcohol consumption and binge drinking during pregnancy. Furthermore, as no safe level of drinking during pregnancy has been established, the most conservative advice for women is not to drink alcohol during pregnancy. However, the present study suggests that small volumes consumed occasionally may not present serious concern.

OBJECTIVE: To examine the effects of low to moderate maternal alcohol consumption and binge drinking in early pregnancy on children's executive functions at the age of 5 years. DESIGN: Follow-up study. SETTING: Neuropsychological testing in four Danish cities 2003-2008. POPULATION: A cohort of 1628 women and their children sampled from the Danish National Birth Cohort. METHODS: Participants were sampled based on maternal alcohol drinking patterns during early pregnancy. When the children were 5 years old, the parent and teacher forms of the Behaviour Rating Inventory of Executive Function (BRIEF) were completed by the mothers and a preschool teacher. Parental education, maternal IQ, prenatal maternal smoking, the child's age at testing, and the child's gender were considered core confounding factors. The full model also included maternal binge drinking or low to moderate alcohol consumption, maternal age, parity, maternal marital status, family home environment, postnatal parental smoking, pre-pregnancy maternal body mass index (BMI), and the health status of the child. Main outcome measures The BRIEF parent and teacher forms. RESULTS: Adjusted for all potential confounding factors, no statistically significant associations between maternal low to moderate average weekly consumption and BRIEF index scores were observed. In adjusted analyses, binge drinking in gestational week 9 or later was significantly associated with elevated Behavioural Regulation Index parent scores (OR 2.04, 95% CI 0.33-3.76), and with the risk of high scores on the Metacognitive Index assessed by the teacher (OR 2.06, 95% CI 1.01-4.23). CONCLUSIONS: This study did not observe significant effects of low to moderate alcohol consumption during pregnancy on executive functioning at the age of 5 years. Furthermore, only weak and no consistent associations between maternal binge drinking and executive functions were observed.

OBJECTIVE: To examine the effects of low to moderate maternal alcohol consumption during early pregnancy on children's intelligence (IQ) at age 5 years. DESIGN: Prospective follow-up study. SETTING: Neuropsychological testing in four Danish cities 2003-2008. POPULATION: A cohort of 1628 women and their children sampled from the Danish National Birth Cohort. METHODS: Participants were sampled based on maternal alcohol consumption during pregnancy. At 5 years of age, children were tested with the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R). Parental education, maternal IQ, maternal smoking in pregnancy, the child's age at testing, gender, and tester were considered core confounding factors, whereas the full model also controlled for maternal binge drinking, age, BMI, parity, home environment, postnatal smoking in the home, health status, and indicators for hearing and vision impairments. MAIN OUTCOME MEASURES: The WPPSI-R. RESULTS: No differences in test performance were observed between children whose mothers reported consuming between one and four or between five and eight drinks per week at some point during pregnancy, compared with children of mothers who abstained. For women who reported consuming nine or more drinks per week no differences were observed for mean differences; however, the risks of low full-scale IQ (OR 4.6; 95% CI 1.2-18.2) and low verbal IQ (OR 5.9; 95% CI 1.4-24.9) scores, but not low performance IQ score, were increased. CONCLUSIONS: Maternal consumption of low to moderate quantities of alcohol during pregnancy was not associated with the mean IQ score of preschool children. Despite these findings, acceptable levels of alcohol use during pregnancy have not yet been established, and conservative advice for women continues to be to avoid alcohol use during pregnancy.

The National Children's Study (NCS) is a national longitudinal study that will prospectively investigate the influence of biological, environmental, genetic, and social factors on the health and development of US children. The NCS was mandated by the Children's Health Act of 2000 (Public Law 106-310) and is being implemented by the National Institutes of Health with input from the Centers for Disease Control and Prevention (CDC), the Environmental Protection Agency, and other federal departments and agencies. The NCS is a data-driven, evidence-based, community- and participant-informed study. Given its scale and scope, the NCS is an integrated system using several data acquisition strategies intended to provide evidenced-based design of methodologies and protocols. These strategies include the Vanguard Study, the Main Study, and formative research and sub-studies. The Vanguard Study, a pilot study, is currently underway and has been expanded from 7 to 37 study locations. The original study protocols and recruitment strategy have been field tested and revisions are under consideration. The CDC is collaborating with NCS in a pilot study that evaluates biological specimen protocols and will provide results on a broad array of environmental chemical exposures and nutritional indicators for a sample of Vanguard Study participants. This study is an example of the kind of collaborative opportunity that would benefit the NCS. Medical toxicologists have unique training in basic and clinical toxicology and laboratory assessments, and by partnering with study centers, both the NCS design and future NCS research projects could be enhanced.

BACKGROUND: To examine the effects of low to moderate alcohol consumption during pregnancy on child motor function at age 5. METHODS: A prospective follow-up study of 685 women and their children sampled from the Danish National Birth Cohort based on maternal alcohol consumption during pregnancy. At 5 years of age, the children were tested with the "Movement Assessment Battery for Children" (MABC). Parental education, maternal IQ, prenatal maternal smoking, the child's age at testing, and gender of child were considered core confounders, while the full model also controlled for prenatal maternal binge drinking episodes, age, maternal prepregnancy body mass index, parity, home environment, postnatal parental smoking, health status, and indicators for hearing and vision impairment. RESULTS: There were no systematic or significant differences in motor function between children of mothers reporting low to moderate levels of average alcohol consumption during pregnancy and children of mothers who abstained. CONCLUSIONS: In this study, we found no systematic association between low to moderate maternal alcohol intake during pregnancy and child motor function at age 5.

Tobacco smoke is a major source of adult exposure to cadmium (Cd). Urine Cd levels (CdU) above 1.0, 0.7, and 0.5mugCd/g creatinine have been associated with increased rates of microproteinuria and reduction in glomerular filtration rate. The two study objectives were to determine the prevalence and relative risk (RR) by smoking status for CdU above 1.0, 0.7, and 0.5mugCd/g creatinine in U.S. adults; and to describe geometric mean CdU by smoking status, age, and sex. NHANES 1999-2006 data for adults without chronic kidney disease were used to compute prevalence rates above the three CdU in current and former cigarette smokers, and non-smokers. RRs for smokers adjusted for age and sex were computed by logistic regression. Analysis of covariance was used to calculate geometric means of CdU adjusted for age, sex, smoking status, log urine creatinine, and interaction terms: age-smoking status and sex-smoking status. At selected ages, adjusted RR for exceeding each risk-associated CdU was highest for current smokers (3-13 times), followed by former smokers (2-3 times), compared to non-smokers. Adjusted RR for smokers increased with age and was higher in females than males. Adjusted geometric means of CdUs increased with age, were higher in females than in males regardless of smoking status, and were higher in current smokers than former smokers, who had higher levels than non-smokers at any age. Cigarette smoking greatly increases RR of exceeding renal risk-associated CdU. Former smokers retain significant risk of exceeding these levels compared to non-smokers. CdU increased with age, particularly in current smokers.

Concern for children exposed to elemental mercury prompted the Agency for Toxic Substances and Disease Registry and the Centers for Disease Control and Prevention to review the sources of elemental mercury exposures in children, describe the location and proportion of children affected, and make recommendations on how to prevent these exposures. In this review, we excluded mercury exposures from coal-burning facilities, dental amalgams, fish consumption, medical waste incinerators, or thimerosal-containing vaccines. We reviewed federal, state, and regional programs with data on mercury releases along with published reports of children exposed to elemental mercury in the United States. We selected all mercury-related events that were documented to expose (or potentially expose) children. Primary exposure locations were at home, at school, and at others such as industrial property not adequately remediated or medical facilities. Exposure to small spills from broken thermometers was the most common scenario; however, reports of such exposures are declining. The information reviewed suggests that most releases do not lead to demonstrable harm if the exposure period is short and the mercury is properly cleaned up. Primary prevention should include health education and policy initiatives.

We describe the distribution and demographic characteristics of total blood Hg levels in the U.S. general population among persons ages 1 year and older who participated in the 2003-2006 National Health and Nutrition Examination Survey (NHANES). We also describe trends in the total blood Hg of children ages 1-5 (n=3456) and females ages 16-49 during 1999-2006 (n=7245). In the combined 2003-2006 survey periods, the geometric means for non-Hispanic blacks, 0.853microg/L (95% confidence interval [CI], 0.766-0.950microg/L), and non-Hispanic whites, 0.833microg/L (95% CI, 0.752-0.922microg/L), were higher than the geometric mean for Mexican Americans, 0.580microg/L (95% CI, 0.522-0.645microg/L). Also in 2003-2006, regression analysis of log total blood Hg with age, race/ethnicity and gender showed that total blood Hg levels in the population exhibited a quadratic increase with age (p<0.0001), peaking at ages 50-59 in non-Hispanic blacks and whites, at ages 40-49 in Mexican Americans, and then declining at older ages. Over the four survey periods (1999-2006), regression analysis showed that total blood Hg levels increased slightly for non-Hispanic white children and decreased slightly for non-Hispanic black and Mexican American children. Over the same four survey periods, female children had slightly higher total blood Hg levels than males (0.356 vs. 0.313microg/L, p=0.0050) and total blood Hg levels in non-Hispanic black women aged 16-49 years were significantly higher than in non-Hispanic white women (1.081 vs. 0.850microg/L, p<0.0001) and in Mexican American women (1.081 vs. 0.70microg/L, p<0.0001).