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Additional file 1: Table S1. Comparison of BASC score distributions between the UGAAR population and the reference population. Table S2. Effects of the air cleaner intervention on BASC composite scores at ages 2 and 4 estimated from a mixed effects model among complete cases. Table S3. Comparison of baseline characteristics for participants who did and did not complete the BASC. Figure S1. Directed acyclic graph used to identify adjustment variables in models of the association between PM2.5 and BASC scores. Figure S2. Data analysis scheme for intention-to-treat analyses of combined 2-year and 4-year BASC scores using linear mixed effects models.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are persistent environmental pollutants used as flame retardants. Gestational PBDE exposure has been associated with a variety of behavior problems in children, but little is known about its impact into adolescence, particularly on social skills, which are important for achieving social competence, establishing identity, and forming lasting relationships. OBJECTIVE: We investigated associations between gestational exposure to PBDEs and social skills and problem behaviors in early adolescence in a longitudinal pregnancy and birth cohort in Cincinnati, Ohio (recruited 2003–2006). METHODS: We measured maternal serum concentrations of five PBDE congeners during gestation. At age 12, we collected social skills and problem behaviors scores from 243 adolescents and their caregivers using the Social Skills Improvement System (SSiS). We used multivariable linear regression models to estimate associations between maternal PBDE concentrations and SSiS outcomes, controlling for potential covariates. We report associations for the five congeners and a summary exposure variable (∑(5)BDE: the sum of BDE- 28, 47, 99, 100, and 153, n=197). RESULTS: We found sex-specific associations of ∑(5)BDE concentrations with adolescent-reported Problem Behaviors (∑(5)BDE × sex p(int)=0.02) and caregiver-reported Social Skills (∑(5)BDE × sex p(int)=0.02) despite higher ∑(5)BDE exposure among females (Male GM=35.30 ng/g lipid, GSE=1.09; Female GM=40.15 ng/g lipid, GSE=1.10). In sex-stratified models, log(10) transformed data revealed increased maternal ∑(5)BDE concentration among males was associated with decreased caregiver-reported Social Skills composite score (β=−10.2, 95% CI: −19.5, −1.0), increased adolescent-reported Problem Behaviors composite score (β=12.1, 95% CI: 5.4, 18.8), and increased caregiver-reported Problem Behaviors composite score (β=6.2, 95% CI: 0.7, 11.7). Further analysis on SSiS subscales revealed similar patterns in significant associations among males. There were no statistically significant associations in stratified models among females. DISCUSSION: We found gestational PBDE exposure in males was associated with poorer behavioral outcomes, extending previous findings among this cohort into early adolescence.

Supplemental Table 1. Baseline characteristics of mother-child pairs in the HOME Study according inclusion vs. exclusion status. Supplemental Table 2. Proportion of children who were overweight or obese at ages 4 weeks to 5 years according to World Health Organization definitionsa. Supplemental Table 3. Univariate Statistics of BMI Z-scores at each Study Visit According to Childrenâ s Overweight/Obesity Status Assessed by WHO BMI z-score at Age 8 Yearsa. Supplemental Table 4. Univariate Statistics of BMI Z-scores at each Study Visit According to Childrenâ s Overweight/Obesity Status Assessed by Bioelectric Impedance at Age 8 Yearsa. Supplemental Figure 1. Flowchart describing study participant selection in present study. (DOCX 79 kb)

Additional data visualizations including DAG, correlation heat map, and LASSO and Elastic Net figures and tables for secondary sex-stratified analysis. (DOCX 331 kb)

Summary: Children in America today are at an unacceptably high risk of developing neurodevelopmental disorders that affect the brain and nervous system including autism, attention deficit hyperactivity disorder, intellectual disabilities, and other learning and behavioral disabilities. These are complex disorders with multiple causes—genetic, social, and environmental. The contribution of toxic chemicals to these disorders can be prevented. Approach: Leading scientific and medical experts, along with children’s health advocates, came together in 2015 under the auspices of Project TENDR: Targeting Environmental Neuro-Developmental Risks to issue a call to action to reduce widespread exposures to chemicals that interfere with fetal and children’s brain development. Based on the available scientific evidence, the TENDR authors have identified prime examples of toxic chemicals and pollutants that increase children’s risks for neurodevelopmental disorders. These include chemicals that are used extensively in consumer products and that have become widespread in the environment. Some are chemicals to which children and pregnant women are regularly exposed, and they are detected in the bodies of virtually all Americans in national surveys conducted by the U.S. Centers for Disease Control and Prevention. The vast majority of chemicals in industrial and consumer products undergo almost no testing for developmental neurotoxicity or other health effects. Conclusion: Based on these findings, we assert that the current system in the United States for evaluating scientific evidence and making health-based decisions about environmental chemicals is fundamentally broken. To help reduce the unacceptably high prevalence of neurodevelopmental disorders in our children, we must eliminate or significantly reduce exposures to chemicals that contribute to these conditions. We must adopt a new framework for assessing chemicals that have the potential to disrupt brain development and prevent the use of those that may pose a risk. This consensus statement lays the foundation for developing recommendations to monitor, assess, and reduce exposures to neurotoxic chemicals. These measures are urgently needed if we are to protect healthy brain development so that current and future generations can reach their fullest potential.

Over the past 3 decades, in a series of studies on some of the most extensively studied toxic chemicals and pollutants, scientists have found that the amount of toxic chemical linked with the development of a disease or death-which is central to determining "safe" or "hazardous" levels-is proportionately greater at the lowest dose or levels of exposure. These results, which are contrary to the way the United States Environmental Protection Agency (EPA) and other regulatory agencies assess the risk of chemicals, indicate that we have underestimated the impact of toxic chemicals on death and disease. If widely disseminated chemicals and pollutants-like radon, lead, airborne particles, asbestos, tobacco, and benzene-do not exhibit a threshold and are proportionately more toxic at the lowest levels of exposure, we will need to achieve near-zero exposures to protect public health.

Background: Environmental lead exposure, measured using blood lead concentration, is an established risk factor for hypertension, but the relation of blood lead concentration with cardiovascular di...

Background: Endocrine disrupting chemicals (EDCs) may increase the risk of autism, possibly by perturbing fetal hormone signaling or metabolism, but this complex exposure mixture makes identifying ...

Background: Phthalates are used in PVC plastics, food packaging, and personal care products. Use of phthalates in certain children’s products has been regulated in some countries due to possible to...

Background: Perfluoroalkyl acids (PFASs) are known thyroid toxicants in animal studies, but the effect of PFASs on human thyroid hormones is unclear. Aims: To examine PFAS-thyroid hormone associati...

Background Childhood lead exposure is a purported risk factor for antisocial behavior, but prior studies either relied on indirect measures of exposure or did not follow participants into adulthood to examine the relationship between lead exposure and criminal activity in young adults. The objective of this study was to determine if prenatal and childhood blood lead concentrations are associated with arrests for criminal offenses. Methods and Findings Pregnant women were recruited from four prenatal clinics in Cincinnati, Ohio if they resided in areas of the city with a high concentration of older, lead-contaminated housing. We studied 250 individuals, 19 to 24 y of age, out of 376 children who were recruited at birth between 1979 and 1984. Prenatal maternal blood lead concentrations were measured during the first or early second trimester of pregnancy. Childhood blood lead concentrations were measured on a quarterly and biannual basis through 6.5 y. Study participants were examined at an inner-city pediatric clinic and the Cincinnati Children's Hospital Medical Center in Cincinnati, Ohio. Total arrests and arrests for offenses involving violence were collected from official Hamilton County, Ohio criminal justice records. Main outcomes were the covariate-adjusted rate ratios (RR) for total arrests and arrests for violent crimes associated with each 5 μg/dl (0.24 μmol/l) increase in blood lead concentration. Adjusted total arrest rates were greater for each 5 μg/dl (0.24 μmol/l) increase in blood lead concentration: RR = 1.40 (95% confidence interval [CI] 1.07–1.85) for prenatal blood lead, 1.07 (95% CI 0.88–1.29) for average childhood blood lead, and 1.27 (95% CI 1.03–1.57) for 6-year blood lead. Adjusted arrest rates for violent crimes were also greater for each 5 μg/dl increase in blood lead: RR = 1.34 (95% CI 0.88–2.03) for prenatal blood lead, 1.30 (95% CI 1.03–1.64) for average childhood blood lead, and 1.48 (95% CI 1.15–1.89) for 6-year blood lead. Conclusions Prenatal and postnatal blood lead concentrations are associated with higher rates of total arrests and/or arrests for offenses involving violence. This is the first prospective study to demonstrate an association between developmental exposure to lead and adult criminal behavior., Kim Dietrich and colleagues find an association between developmental exposure to lead and adult criminal behavior., Editors' Summary Background. Violent crime is an increasing problem in many countries, but why are some people more aggressive than others? Being male has been identified as a risk factor for violent criminal behavior in several studies, as have exposure to tobacco smoke before birth, having antisocial parents, and belonging to a poor family. Another potential risk factor for antisocial behavior as an adult is exposure to lead during childhood, although few studies have looked directly at whether childhood lead exposure is linked with criminal behavior in adulthood. Lead is a toxic metal that damages the nervous system when ingested or inhaled. It is present throughout the environment because of its widespread use in the past in paint, solder for water pipes, and gasoline. In 1978, 13.5 million US children had a blood lead level above 10 μg/dl, the current US Centers for Disease Control and Prevention blood lead level of concern (the average US blood lead level is 2 μg/dl). Lead paint and solder were banned in 1978 and 1986, respectively, by the US federal government; leaded gasoline was finally phased out in 1996. By 2002, only 310,000 US children had a blood lead level above 10 μg/dl. However, children exposed to lower levels of lead than this—through ingesting flakes or dust residues of old lead paint, for example—can have poor intellectual development and behavioral problems including aggression. Why Was This Study Done? Although some studies have suggested that childhood lead exposure is associated with later criminal behavior, these studies have often relied on indirect measurements of childhood lead exposure such as bone lead levels in young adults or a history of lead poisoning. Other studies that have measured childhood lead exposure directly have not followed their participants into adulthood. In this new study, the researchers investigate the association between actual measurements of prenatal and childhood blood lead concentrations and criminal arrests in early adulthood to get a clearer idea about whether early lead exposure is associated with subsequent violent behavior. What Did the Researchers Do and Find? Between 1979 and 1984, the researchers recruited pregnant women living in poor areas of Cincinnati, which had a high concentration of older, lead-contaminated housing, into the Cincinnati Lead Study. They measured the women's blood lead concentrations during pregnancy as an indication of their offspring's prenatal lead exposure and the children's blood lead levels regularly until they were six and half years old. They then obtained information from the local criminal justice records on how many times each of the 250 offspring had been arrested between becoming 18 years old and the end of October 2005. The researchers found that increased blood lead levels before birth and during early childhood were associated with higher rates of arrest for any reason and for violent crimes. For example, for every 5 μg/dl increase in blood lead levels at six years of age, the risk of being arrested for a violent crime as a young adult increased by almost 50% (the “relative risk” was 1.48). What Do These Findings Mean? These findings provide strong evidence that early lead exposure is a risk factor for criminal behavior, including violent crime, in adulthood. One possibility, which the authors were unable to assess in this study, is that lead exposure impairs intelligence, which in turn makes it more likely that a criminal offender will be caught (i.e., arrested). The authors discuss a number of limitations in their study—for example, they probably did not capture all criminal behavior (since most criminal behavior does not lead to arrest). Although both environmental lead levels and crime rates have dropped over the last 30 years in the US, the overall reduction was not uniform—inner-city children remain particularly vulnerable to lead exposure. The findings therefore suggest that a further reduction in childhood lead exposure might be an important and achievable way to reduce violent crime. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050101. A PLoS Medicine Perspective article by David Bellinger further discusses this study and a related paper on childhood lead exposure and brain volume reduction in adulthood Study researcher Kim Dietrich can be heard talking about “The Lethal Legacy of Lead”, a brief MP3 about lead exposure and violent crime Toxtown, an interactive site from the US National Library of Medicine, provides information on environmental health concerns including exposure to lead (in English and Spanish) The US Environmental Protection Agency provides information on lead in paint, dust, and soil and on protecting children from lead poisoning (in English and Spanish) MedlinePlus provides a list of links to information on lead poisoning (in English and Spanish) The US Centers for Disease Control and Prevention provides information about its Childhood Lead Poisoning Prevention Program The UK Health Protection Agency also provides information about lead and its health hazards

OBJECTIVE: To evaluate the effect of soil abatement on children's blood lead concentrations and on environmental levels of lead and arsenic. METHODS: Two cross-sectional surveys were conducted. The first (1989) was of a random sample of 6- to 72-month-old children (n=112). The second (1998) included all 6- to 72-month-old children whose parents agreed to participate in the survey (n=215). From 1993 to 1996, soil abatement was conducted around homes with average soil lead concentration >500 parts per million (ppm). Venipuncture blood samples were taken, interviews were conducted, and samples of house dust, soil, water, and paint were tested for lead and arsenic, using identical protocols in both surveys. The expected decline in blood lead concentrations were calculated for children who lived in houses that were abated, compared with children who lived in houses that were not abated. RESULTS: Lead and arsenic in soil and interior dust in homes that underwent soil abatement declined significantly compared to unabated homes (p

Supplemental Table 1. Baseline characteristics of mother-child pairs in the HOME Study according inclusion vs. exclusion status. Supplemental Table 2. Proportion of children who were overweight or obese at ages 4 weeks to 5 years according to World Health Organization definitionsa. Supplemental Table 3. Univariate Statistics of BMI Z-scores at each Study Visit According to Childrenâ s Overweight/Obesity Status Assessed by WHO BMI z-score at Age 8 Yearsa. Supplemental Table 4. Univariate Statistics of BMI Z-scores at each Study Visit According to Childrenâ s Overweight/Obesity Status Assessed by Bioelectric Impedance at Age 8 Yearsa. Supplemental Figure 1. Flowchart describing study participant selection in present study. (DOCX 79 kb)