Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children.OBJECTIVE: The purpose of this study was to examine the association of exposures to tobacco smoke and environmental lead with attention deficit hyperactivity disorder attention deficit hyperactivity disorder (ADHD), formerly called hyperkinesis or minimal brain dysfunction, a chronic, neurologically based syndrome characterized by any or all of three types of behavior: hyperactivity, distractibility, and impulsivity. (ADHD Attention-Deficit/Hyperactivity Disorder (ADHD) Definition Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterized by distractibility, hyperactivity, impulsive behaviors, and the inability to remain focused on tasks or ). METHODS: Data were obtained from the National Health and Nutrition Examination Survey 1999-2002. Prenatal and postnatal postnatal /post·na·tal/ (-na´t'l) occurring after birth, with reference to the newborn. post·na·tal adj. Of or occurring after birth, especially in the period immediately after birth. tobacco exposure was based on parent report; lead exposure was measured using blood lead concentration. ADHD was defined as having current stimulant stimulant, any substance that causes an increase in activity in various parts of the nervous system or directly increases muscle activity. Cerebral, or psychic, stimulants act on the central nervous system and provide a temporary sense of alertness and well-being as medication use and parent report of ADHD diagnosed by a doctor or health professional. RESULTS: Of 4,704 children 4-15 years of age, 4.2% were reported to have ADHD and stimulant medication use, equivalent to 1.8 million children in the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area. . In multivariable analysis, prenatal tobacco exposure [odds ratio (OR) = 2.5; 95% confidence interval confidence interval, n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%. (CI), 1.2-5.2] and higher blood lead concentration (first vs. fifth quintile quin·tile n. 1. The astrological aspect of planets distant from each other by 72° or one fifth of the zodiac. 2. Statistics The portion of a frequency distribution containing one fifth of the total sample. , OR = 4.1; 95% CI, 1.2-14.0) were significantly associated with ADHD. Postnatal tobacco smoke exposure was not associated with ADHD (OR = 0.6; 95% CI, 0.3-1.3; p = 0.22). If causally linked, these data suggest that prenatal tobacco exposure accounts for 270,000 excess cases of ADHD, and lead exposure accounts for 290,000 excess cases of ADHD in U.S. children. CONCLUSIONS: We conclude that exposure to prenatal tobacco and environmental lead are risk factors for ADHD in U.S. children. KEY WORDS: ADHD, attention deficit hyperactivity disorder, blood lead, children, environmental tobacco smoke environmental tobacco smoke (ETS/passive smoke), n the gaseous by-product of burning tobacco products, including but not limited to commercially manufactured cigarettes and cigars; contains toxic elements harmful to the health of adults and children , lead poisoning lead poisoning or plumbism (plŭm`bĭz'əm), intoxication of the system by organic compounds containing lead. , NHANES NHANES National Health and Nutrition Examination Survey (US CDC) , prenatal tobacco exposure, tobacco. Environ Health Perspect 114:1904-1909 (2006). doi:10.1289/ehp.9478 available via http://dx.doi.org/ [Online 19 September 2006] ********** Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood disorders, with an estimated prevalence ranging from 3 to 8% [American Psychiatric Association The American Psychiatric Association (APA) is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the most influential world-wide. Its some 148,000 members are mainly American but some are international. (APA (All Points Addressable) Refers to an array (bitmapped screen, matrix, etc.) in which all bits or cells can be individually manipulated. APA - Application Portability Architecture ) 1994; Costello et al. 2003; Lesesne et al. 2003; Olfson et al. 2003; Pastor and Reuben 2002; Rowland et al. 2002; Wolraich et al. 1996]. Children who have ADHD are at increased risk for conduct disorder Conduct Disorder Definition Conduct disorder (CD) is a behavioral and emotional disorder of childhood and adolescence. Children with conduct disorder act inappropriately, infringe on the rights of others, and violate the behavioral expectations of , antisocial antisocial /an·ti·so·cial/ (-so´sh'l) 1. denoting behavior that violates the rights of others, societal mores, or the law. 2. denoting the specific personality traits seen in antisocial personality disorder. behavior, and drug abuse later in life (Costello et al. 2003; Mannuzza 1993). Moreover, the costs associated with their medical care and education are substantial (Leibson et al. 2001). Although the mechanisms for the development of ADHD remain unclear, both genetic and environmental factors have been implicated im·pli·cate tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates 1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot. 2. (Ernst et al. 2001). Numerous studies have found a significant association between prenatal environmental tobacco smoke (ETS ETS Educational Testing Service (nonprofit private educational testing and measurement organization) ETS Emergency Telecommunications Service ETS Electronic Trading System ETS Engineering (&) Technical Services ) exposure and ADHD or ADHD-related behaviors, even after controlling for postnatal ETS exposures and familial psychopathology psychopathology /psy·cho·pa·thol·o·gy/ (-pah-thol´ah-je) 1. the branch of medicine dealing with the causes and processes of mental disorders. 2. abnormal, maladaptive behavior or mental activity. (Day et al. 2000; Fergusson et al 1993b; Kotimaa et al. 2003; Leech leech, predacious or parasitic annelid worm of the class Hirudinea, characterized by a cylindrical or slightly flattened body with suckers at either end for attaching to prey. et al. 1999; Mick et al. 2002a; Milberger et al. 1996, 1998; Thapar et al. 2003; Wasserman et al. 2001; Williams et al. 1998). In case-control studies, investigators have found a 2-to 4-fold increased risk for ADHD associated with prenatal ETS exposure (Mick et al. 2002a; Milberger et al. 1996, 1998). In contrast, the relationship between postnatal ETS exposure and children's behavior problems has not been fully elucidated (Day et al. 2000; Fergusson et al 1993b; Weitzman et al. 1992; Williams et al. 1998). Moreover, the attributable fraction of childhood ADHD due to ETS exposure is unknown. Environmental lead exposure, measured in blood or dentin dentin /den·tin/ (den´tin) the chief substance of the teeth, surrounding the tooth pulp and covered by enamel on the crown and by cementum on the roots.den´tinal adventitious dentin secondary d. , has been associated with higher rates of inattention in·at·ten·tion n. Lack of attention, notice, or regard. Noun 1. inattention - lack of attention basic cognitive process - cognitive processes involved in obtaining and storing knowledge and impulsivity (Bellinger et al. 1994; Fergusson et al. 1993a; Needleman et al. 1979; Wasserman et al. 1998, 2001). Although lead exposure is often cited as a risk factor for ADHD, existing studies examining the association of lead exposure with a diagnosis of ADHD, which were limited by small sample size, are inconclusive (David et al. 1972; Gittleman and Eskenazi 1983). Moreover, many of the studies examining the association of lead exposure with inattention or impulsivity involved children who had higher blood lead levels than the levels seen in contemporary children, and thus may not be directly relevant to children with lower levels of lead exposure (Bellinger et al. 1994; Needleman et al. 1979; Fergusson et al. 1993a; Wasserman et al. 1998, 2001). Although several recent studies have linked lead to IQ deficits at blood lead levels < 10 [micro]g/dL (Bellinger and Needleman 2003; Canfield et al. 2003; Lanphear et al. 2005)--the current action level set by the Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. (CDC See Control Data, century date change and Back Orifice. CDC - Control Data Corporation )--it remains unclear whether blood lead levels < 10 [micro]g/dL are also associated with behavioral problems in children (CDC 2005b). Studies investigating the effect of environmental exposures on neurobehavioral outcomes have been complicated by evidence from both animal and human studies that toxicants may have differing effects in male and female subjects (Burns et al. 1999; Ernst 2001; McCartney 1999; O'Callaghan et al. 1992; Ribary and Lichtensteiger 1989; Ris et al. 2004; Weissman et al. 1999). The prevalence of ADHD is three times greater among males than among females (Costello et al. 2003; Lesesne et al. 2003; Olfson et al. 2003; Pastor and Reuben 2002). Some studies have documented varying behavioral effects of prenatal ETS exposure in males and females (Fergusson et al. 1998; Weissman et al. 1999), whereas other studies have not (Mick et al. 2002a; Milberger et al. 1996, 1998; Orlebeke et al. 1999). Studies of lead exposure's effects have been similarly complicated: There is some evidence that males are at increased risk for externalizing behaviors (Burns et al. 1999) and attentional problems (Ris et al. 2004) from lead exposure, but the results are not entirely consistent. The purpose of this study was to explore the relationship between exposure to ETS and environmental lead with ADHD using a large nationally representative sample of children. We also explored whether sex modifies the relationships between these neurotoxicants and ADHD. Finally we provide estimates of population attributable fraction of prenatal ETS exposure and lead exposure for ADHD in U.S. children. Methods Data source. The data for this analysis came from the National Health and Nutrition Examination Survey (NHANES), conducted from 1999 to 2002. The NHANES is a cross-sectional household survey of the noninstitutionalized civilian population. NHANES used a complex, multistage mul·ti·stage adj. 1. Functioning in more than one stage: a multistage design project. 2. Relating to or composed of two or more propulsion units. probability sampling design, with oversampling Creating a more accurate digital representation of an analog signal. In order to work with real-world signals in the computer, analog signals are sampled some number of times per second (frequency) and converted into digital code. of children (< 5 years of age), Mexican Americans This is a list of notable Mexican-Americans. Athletes Baseball players
Assessment of ADHD and exposures to environmental toxicants. The primary dependent variables that we used to assess ADHD status were parent report of a diagnosis of ADHD and stimulant medication use. Parent-reported ADHD was based on the parent or guardian's response to the question "Has a doctor or health professional ever told you that your child had attention deficit disorder attention deficit (hyperactivity) disorder (ADD or ADHD) formerly hyperactivity Behavioral syndrome in children, whose major symptoms are inattention and distractibility, restlessness, inability to sit still, and difficulty concentrating on one thing for any ?" To improve the specificity of the diagnosis of parent- reported ADHD, we used parent-reported ADHD and stimulant medication use as the main outcome. Stimulant medication use was based on National Drug Codes 03700, 17900, 39500, and 82000 (CDC 2005a). These codes correspond to amphetamine amphetamine (ămfĕt`əmēn), any one of a group of drugs that are powerful central nervous system stimulants. Amphetamines have stimulating effects opposite to the effects of depressants such as alcohol, narcotics, and barbiturates. aspartate/amphetamine sulfate/dextroamphetamine aspartate/dextroamphetamine sulfate sulfate, chemical compound containing the sulfate (SO4) radical. Sulfates are salts or esters of sulfuric acid, H2SO4, formed by replacing one or both of the hydrogens with a metal (e.g., sodium) or a radical (e.g., ammonium or ethyl). , dextroamphetamine sulfate dex·tro·am·phet·a·mine sulfate n. A white crystalline isomer of amphetamine that acts as a central nervous stimulant and is used to treat narcolepsy and attention deficit hyperactivity disorder. Also called dexamphetamine sulfate. , methylphenidate hydrochloride methylphenidate hydrochloride Concerta, Daytrana, Equasym (UK), Metadate CD, Metadate ER, Methylin, Methylin ER, PHL-Methylphenidate (CA), PMS-Methylphenidate (CA), Riphenidate (CA), Ritalin, Ritalin LA, Ritalin-SR Pharmacologic class: , and unspecified ADHD medication, respectively. Children who had only stimulant medication use or parent report of ADHD were excluded from the primary analysis. Secondary analyses investigated report of ADHD diagnosis and ADHD medication use as separate outcomes to confirm the validity of our primary analysis results. We used parent report to measure children's exposure to tobacco products. Measurement of prenatal ETS exposure consisted of the question "Did the child's biological mother smoke at any time while she was pregnant with him/her?" No information on the quantity or brand of cigarettes smoked during pregnancy was collected. We assessed postnatal ETS exposure using parent-reported exposure to household ETS by asking "Does anyone who lives here smoke cigarettes, cigars, or pipes anywhere inside this home?" In a secondary analysis, we explored using the child's serum cotinine cotinine (kō´tinēn), n a substance that remains in body fluids after nicotine has been used. Presence of this chemical in body fluids is considered proof of recent nicotine use. concentration, a metabolite metabolite, organic compound that is a starting material in, an intermediate in, or an end product of metabolism. Starting materials are substances, usually small and of simple structure, absorbed by the organism as food. of nicotine, as a biomarker of ETS exposure (Bernert et al 2000). All children with cotinine values < 0.05 ng/mL were imputed Attributed vicariously. In the legal sense, the term imputed is used to describe an action, fact, or quality, the knowledge of which is charged to an individual based upon the actions of another for whom the individual is responsible rather than on the individual's from the left tail of the log-normal distribution In probability and statistics, the log-normal distribution is the single-tailed probability distribution of any random variable whose logarithm is normally distributed. If Y is a random variable with a normal distribution, then X = exp(Y using Cohen's method (Cohen cohen or kohen (Hebrew: “priest”) Jewish priest descended from Zadok (a descendant of Aaron), priest at the First Temple of Jerusalem. The biblical priesthood was hereditary and male. 1959). We focused primarily on reported presence of a smoker in the home as the independent variable because serum cotinine values were missing for 921 children. We determined blood lead concentration by graphite furnace atomic absorption Graphite furnace atomic absorption spectrometry (GFAAS) (also known as Electrothermal Atomic Absorption Spectrometry (ETAAS)) is a type of spectrometry that uses a graphite-coated furnace to vaporize the sample. spectrophotometry spectrophotometry Branch of spectroscopy dealing with measurement of radiant energy transmitted or reflected by a body as a function of wavelength. The measurement is usually compared to that transmitted or reflected by a system that serves as a standard. (Miller et al. 1987; Parsons and Slavin 1993). The limit of detection was reported to be 0.3 [micro]g/dL: 48 children had blood lead levels below this threshold. Nondetectable values were given values of 0.2 (0.3 divided by [square root of 2]). Covariates. We examined multiple covariates and potential confounders for the association of prenatal ETS exposure and lead exposure with ADHD. Demographic variables included the child's age, sex, race, and socioeconomic status socioeconomic status, n the position of an individual on a socio-economic scale that measures such factors as education, income, type of occupation, place of residence, and in some populations, ethnicity and religion. [as measured by poverty-to-income ratio (PIR "Parent in room." See digispeak. )]. PIR is the ratio of family income to the poverty threshold The poverty threshold, or poverty line, is the minimum level of income deemed necessary to achieve an adequate standard of living. In practice, like the definition of poverty, the official or common understanding of the poverty line is significantly higher in developed for the year of the interview. Children with PIR values < 1 are considered to be living below the poverty level. Health insurance coverage was also included as a covariate. In addition, a review of the literature suggested that preschool attendance, low birth weight, and ferritin ferritin /fer·ri·tin/ (-i-tin) the iron-apoferritin complex, one of the chief forms in which iron is stored in the body. fer·ri·tin n. levels (an indicator of iron status) should be considered potential confounders because of their prior documented associations with child behavioral problems and environmental toxicants [Knopik et al. 2005; Kordas et al. 2004; Mick 2002b; National Institute of Child Health and Human Development (NICHD NICHD National Institute of Child Health and Human Development. ) 2003; St. Sauver et al. 2004; Wasserman et al. 2001]. Child's birth weight and admission to a neonatal intensive care unit Noun 1. neonatal intensive care unit - an intensive care unit designed with special equipment to care for premature or seriously ill newborn NICU ICU, intensive care unit - a hospital unit staffed and equipped to provide intensive care (NICU NICU abbr. neonatal intensive-care unit ) were included as markers of perinatal distress. Statistical analysis. We used logistic regression In statistics, logistic regression is a regression model for binomially distributed response/dependent variables. It is useful for modeling the probability of an event occurring as a function of other factors. analysis with a binary outcome of ADHD to identify predictors of ADHD. Variables found to be associated with ADHD based on chi-square (p < 0.2) in bivariable analyses were included in the logistic regression analyses. Postnatal ETS exposure was forced into all multivariable models. Because NICU admission and birth weight may be acting as intervening variables on the pathway from prenatal ETS exposure to ADHD, we included these two variables in secondary analyses to examine whether their inclusion altered our findings (Kiely 1991). We also examined the relationship of lead exposure and ADHD at blood lead levels [less than or equal to] 5 [micro]g/dL in secondary analyses. Among children 4-15 years of age, 5,171 were available for analysis. We found that children who did not have routine access to health care were unlikely to be treated with stimulant medications; therefore, we excluded these children from the main analysis (n = 458). Regression diagnostics were conducted to identify influential observations and collinearity collinearity very high correlation between variables. . Influential observations were excluded from analyses to examine whether their inclusion altered the results (n = 9). The exclusion of these outliers did not significantly influence the estimates of prenatal ETS exposure or environmental lead exposure. After excluding outliers and children without routine access to health care, 4,704 children were available for bivariate bi·var·i·ate adj. Mathematics Having two variables: bivariate binomial distribution. Adj. 1. analyses; of those children, 3,879 had complete data available for multivariate analyses. After developing a multivariable main effects model, we tested for an interaction between sex and prenatal ETS exposure, and between sex and blood lead concentration. For prenatal ETS exposure, we first analyzed the complete sample and modeled the potential interaction using a variable with four categories: unexposed females (reference category), exposed females, unexposed males, and exposed males (Rothman 2002). We also tested whether a formal sex-by-exposure interaction term was statistically significant for blood lead concentration and prenatal ETS exposure. We calculated population-attributable fraction (PAF PAF platelet activating factor. PAF abbr. platelet-aggregating factor PAF platelet activating factor. ) for risk factors independently associated with ADHD using Miettinen's formula (Hanley 2001). Because these independent risk factors are not mutually exclusive Adj. 1. mutually exclusive - unable to be both true at the same time contradictory incompatible - not compatible; "incompatible personalities"; "incompatible colors" of other risk factors, we also estimated the PAF of children having either environmental lead and prenatal ETS exposures. Analyses were performed using the SUDAAN statistical package to account for the multistage, complex sampling design (Research Triangle Institute The Research Triangle Institute (RTI) is a non-profit research organization based in the Research Triangle Park (RTP) of North Carolina. RTI is the oldest tenant of this major research park, and the sister organization to the Research Triangle Foundation. 2004). Sample weights were applied according to according to prep. 1. As stated or indicated by; on the authority of: according to historians. 2. In keeping with: according to instructions. 3. the National Center for Health Statistics National Center for Health Statistics (NCHS) is part of the Centers for Disease Control and Prevention (CDC), which is part of the United States Department of Health and Human Services. NCHS is the United States' principal health statistics agency. guidelines (CDC 2004) to produce accurate national estimates, adjusting for the oversampling of minorities and young children. This study was approved by the National Center for Health Statistics Institutional Review Board, Cincinnati Children's Hospital Medical Center Cincinnati Children's Hospital Medical Center is a hospital in Cincinnati, Ohio. In June of 1883, a meeting of women from parish communities around Cincinnati established a mission to create a Diocesan Hospital for Children. Institutional Review Board, and the University of Milwaukee College of Nursing Institutional Review Board. Consent was obtained from all participants. Results Of the 4,704 eligible children 4-15 years of age, 344 (8.2%) had only parent-reported ADHD and 154 (4.3%) reported stimulant medication use, equivalent to 3.8 million and 2.0 million U.S. children and adolescents, respectively. Of the 4,704 children, 135 (4.2% weighted percent) had parent report of both ADHD and stimulant medication use, equivalent to 1.8 million children in the United States. (Table 1). In bivariate analyses, we found a significant association between parent-reported ADHD and stimulant medication use with prenatal ETS exposure (p = 0.023), preschool attendance (p = 0.003), male sex (p < 0.001), increasing age in years (p < 0.001), and health insurance coverage (p < 0.001) (Table 1). Non-Hispanic white children were more likely than other racial groups to report ADHD (p = 0.001). In multivariable analysis, prenatal ETS exposure and blood lead concentration were significant predictors of ADHD (Table 2). The adjusted odds ratio (AOR AOR The ISO 4217 currency code for Angolan Reajustado Kwanza. ) for prenatal ETS exposure was 2.5 [95% confidence interval (CI), 1.2-5.2]. We also found a significant dose-response relationship The Dose-response relationship describes the change in effect on an organism caused by differing levels of exposure (or doses) to a stressor (usually a chemical). This may apply to individuals (eg: a small amount has no observable effect, a large amount is fatal), or to populations between lead exposure and ADHD (Figure 1). Compared with children in the lowest quintile of blood lead concentration, children with blood lead levels in the fifth quintile (AOR = 4.1; 95% CI, 1.2-14.0) were at significantly higher risk for ADHD. The risk of ADHD was also significantly associated with male sex (AOR = 3.7; 95% CI, 2.1-6.6). Mexican-American and non-Hispanic black children had lower risks for reported ADHD diagnosis and stimulant medication use (AOR = 0.3; 95% CI, 0.1-0.7 and AOR = 0.5; 95% CI, 0.3-0.8, respectively) compared with non-Hispanic white children. Postnatal ETS exposure, as measured by the presence of a smoker in the home, was not a significant predictor of ADHD status in adjusted models (AOR = 0.6; 95% CI, 0.3-1.3; p = 0.224). The risk for ADHD was significantly associated with preschool attendance (AOR = 2.4; 95% CI, 1.1-5.1). Next, we tested for interactions between sex and prenatal exposure to ETS, sex and blood lead concentration, and prenatal exposure to ETS and blood lead concentration. We did not find a significant interaction between prenatal ETS exposure and sex using a formal interaction term (p = 0.141). Compared with unexposed females, females who were prenatally exposed to ETS were at a 4.6-fold higher risk for ADHD compared with unexposed females (OR = 4.6; 95% CI, 1.7-12.4), whereas exposed males were at an almost significant 2-fold higher risk for ADHD than unexposed males (OR = 2.1; 95% CI, 0.9-4.7; p = 0.073) (Figure 2). There was not a significant interaction between blood lead levels by sex (p = 0.242) or blood lead levels by maternal smoking (p = 0.837). We conducted secondary analyses to examine the effects of lead exposure at blood lead levels < 5 [micro]g/dL and to test the stability of our results. When the sample was restricted to children with concurrent blood lead concentrations [less than or equal to] 5 [micro]g/dL, there was still a significant association between higher blood lead levels and ADHD. Compared with children in the lowest quintile (nondetectable to 0.7 [micro]g/dL), children with blood lead levels in the highest quintile (2.0-5 [micro]g/dL) had a 4.5-fold (95% CI, 1.3-15.3) higher risk for ADHD. When birth weight and NICU were added to the primary model, the adjusted OR for prenatal ETS exposure and the fifth quintile of blood lead levels did not change, remaining at 2.2 (95% CI, 1.0-5.1; p = 0.055) and 4.5 (95% CI, 1.3-15.6; p = 0.019), respectively. Consistent with postnatal ETS exposure measured by parent report, postnatal ETS exposure using serum cotinine was not associated with ADHD (AOR = 0.99; 95% CI, 0.97-1.00; p = 0.092). Using the same multivariable model, we found that when the ADHD outcome was defined simply by parent report or by stimulant medication use, rather than the combination of the two, the AOR of maternal smoking and blood lead level did not differ appreciably. Finally, there was no substantive change in the relationship of either prenatal ETS exposure or blood lead concentration when we included children without routine access to health care in the model. The PAF for prenatal ETS exposure for both males and females was 18.4% (95% CI, 5.1-24.8%), corresponding to 270,000 cases of ADHD in children 4-15 years of age (Table 3). Although there was a significant dose-response relationship between lead exposure and ADHD, we estimated the population attributable fraction only for children who had blood lead levels in the fifth quintiles Quintiles Transnational Corp. is a contract research organization which serves the pharmaceutical, biotechnology and healthcare industries. History Quintiles was founded in 1982 by Dennis Gillings and as of 2007 it has 18,000 employees. of blood lead concentration. Our estimates indicate that 21.1% (95% CI, 4.6-25.9%) of ADHD cases among children 4-15 years of age were attributable to having a blood lead > 2.0 [micro]g/dL. This corresponds to 290,000 excess cases of ADHD among U.S. children 4-15 years of age (Table 3). Finally, we calculated the PAF for having either prenatal ETS exposure or blood lead concentration > 2.0 [micro]g/dL to account for children who had both exposures. Our estimates indicate that 32.2% (95% CI, 4.2-41.3%) of ADHD cases among children 4-15 years of age were attributable to having either prenatal ETS exposure or blood lead > 2.0 [micro]g/dL, which corresponds to 480,000 excess cases of ADHD among U.S. children 4-15 years of age. Discussion Overall, 4.2% of children surveyed had parent-reported ADHD and were taking stimulant medication, equivalent to approximately 1.8 million U.S. children in the 4- to 15-yearold population. This rate is consistent with previous estimates of ADHD prevalence, which have ranged from 3 to 8% (APA 1994; Lesesne et al. 2003; Olfson 2003; Pastor and Reuben 2002). Our analysis confirms prior studies linking prenatal ETS exposure with ADHD and, for the first time, demonstrates a significant dose-response relationship between childhood lead exposure and ADHD. In contrast, we did not find a significant association between postnatal ETS exposure and ADHD. In this sample, the overall adjusted risk for ADHD was 2.5-fold higher for children exposed prenatally to ETS, which is consistent with previous case-control studies (Mick et al. 2002a; Milberger et al. 1996, 1998). Previous studies using large cohorts have reported a 1.5-to 2.0-fold increase in risk for behavior problems among children whose mothers smoked during pregnancy, but they did not specifically examine ADHD status (Fergusson et al. 1993b; Weitzman et al. 1992; Williams et al. 1998). Using a large national sample, we confirmed that prenatal ETS exposure was a strong risk factor for ADHD, especially for females. Although the difference in risks by sex was not statistically significant, these results suggest that females may be more susceptible to tobacco-associated ADHD. Females exposed prenatally to ETS had a 4.6-fold increased risk of ADHD compared with unexposed females, whereas males exposed prenatally to ETS were at a 2.1-fold increased risk for ADHD compared with unexposed males. When females are exposed prenatally to ETS, their risk of ADHD becomes equivalent to that of unexposed males. Postnatal ETS exposure was not associated with ADHD in this analysis. We used parent report of household ETS and serum cotinine, but neither was associated with parent-reported ADHD. In previous research, investigators found a significant association of current tobacco consumption of the mother and externalizing behavior problems in children using continuous measures of behavior (Day et al. 2000; Weitzman et al. 1992; Williams et al 1998). It is possible that our results differ because we used a dichotomous di·chot·o·mous adj. 1. Divided or dividing into two parts or classifications. 2. Characterized by dichotomy. di·chot outcome measure, thus limiting our sensitivity to detect an association between postnatal ETS exposure and ADHD-related behavior problems. Furthermore, the cross-sectional measures of reported postnatal ETS exposure and serum cotinine levels may have failed to detect postnatal ETS exposure at critical times in development that may be associated with ADHD or ADHD-related behaviors. We found a significant dose--response relationship of higher blood lead levels and ADHD. Compared with the lowest quintile of blood lead levels, children with blood lead levels > 2.0 [micro]g/dL were at a 4.1-fold increased risk of ADHD. When we limited the analysis to children with blood lead levels [less than or equal to] 5 [micro]g/dL, the association between increased blood lead levels and ADHD remained. These results are consistent with previous reports that have found significant associations between blood or dentin lead levels and behavior problems (Bellinger et al. 1994; Fergusson et al. 1993a; Sood et al. 2001; Wasserman et al. 1998, 2001). Our results further indicate that blood lead levels below the CDC action level of 10 [micro]g/dL are associated with an increased risk for ADHD in children (CDC 2005b). This result is consistent with previous studies that have found cognitive deficits in children with blood lead levels < 10 [micro]g/dL (Canfield et al. 2003; Lanphear et al. 2000, 2005). An interesting finding in this study was the increased likelihood of ADHD for children who attended preschool or child care. Presumably pre·sum·a·ble adj. That can be presumed or taken for granted; reasonable as a supposition: presumable causes of the disaster. , children who attend preschool or child care are more likely to have problem behaviors noted by staff, thus increasing their chance for referral and diagnosis of ADHD by a health professional. Results from the NICHD child care study also suggest that children who are more aggressive and disobedient are more likely to be placed in child care at younger ages and for longer periods of time (NICHD 2003). Regardless of the reason for this finding, staff at these facilities may play an important role in identifying and referring children with behavior problems for early intervention ear·ly intervention n. Abbr. EI A process of assessment and therapy provided to children, especially those younger than age 6, to facilitate normal cognitive and emotional development and to prevent developmental disability or delay. . This study has several limitations. First, the cross-sectional nature of our data makes it difficult to infer a causal relationship from our observed associations. Second, although some might argue that concurrent blood lead tests are not an adequate biomarker of a child's lifetime exposure, recent studies indicate that concurrent blood lead level is a stronger predictor of lead-associated IQ decrements than blood lead measured during early childhood (Chen et al. 2005; Lanphear et al. 2005). Still, the stronger association between neurodevelopment and concurrent lead exposure has been observed only within cognitive domains and not behavioral domains. Third, although we were able to adjust for many important covariates and potential confounders, we were unable to adjust for others, such as maternal alcohol use during pregnancy and parental psychopathology. An additional limitation of our cross-sectional data Cross-sectional data in statistics and econometrics is a type of one-dimensional data set. Cross-sectional data refers to data collected by observing many subjects (such as individuals, firms or countries/regions) at the same point of time, or without regard to differences in time. is susceptibility to recall bias. Mothers of children with behavior problems may be more likely to recall gestational intake of potentially harmful substances, such as tobacco, owing to owing to prep. Because of; on account of: I couldn't attend, owing to illness. owing to prep → debido a, por causa de a drive to identify a cause of their child's disorder. On the other hand, mothers may fail to report tobacco use during pregnancy due to guilt or social stigma Social stigma is severe social disapproval of personal characteristics or beliefs that are against cultural norms. Social stigma often leads to marginalization. Examples of existing or historic social stigmas can be physical or mental disabilities and disorders, as well as (i.e., social desirability bias Social desirability bias is the inclination to present oneself in a manner that will be viewed favorably by others. Being by nature social creatures, people are generally inclined to seek some degree of social acceptance, and as with other psychological terms, "social desirability" ). The reliance of our outcome variable on parent report is also a potential limitation. Nevertheless, by combining parent report of ADHD with stimulant medication use for our main outcome, we maximized the likelihood that all children counted as ADHD cases had been evaluated and diagnosed by a medical professional. On the other hand, these criteria required us to limit our analyses to children with routine access to health care services. Excluding children without routine access to health care enhances the specificity of the diagnosis of ADHD, but it also likely underestimates the total number of ADHD cases that are attributable to prenatal ETS exposure and environmental lead exposure. Using a dichotomous measure of ADHD is less preferable than the administration of a DSM 1. DSM - Data Structure Manager. An object-oriented language by J.E. Rumbaugh and M.E. Loomis of GE, similar to C++. It is used in implementation of CAD/CAE software. DSM is written in DSM and C and produces C as output. (Diagnostic and Statistical Manual of Mental Disorders Diagnostic and Statistical Manual of Mental Disorders /Di·ag·nos·tic and Sta·tis·ti·cal Man·u·al of Men·tal Dis·or·ders/ (DSM) a categorical system of classification of mental disorders, published by the American Psychiatric Association, that delineates objective )-based ADHD diagnostic instrument, which would offer increased specificity to detect behavior problems and specific ADHD subtypes, as well as the possibility of behavioral symptom behavioral symptom Neurology In Alzheimer's disease, any of the Sx that relate to action or emotion, such as wandering, depression, anxiety, hostility, sleep disturbances. See Alzheimer's disease. counts. More continuous measures of ADHD symptoms or of specific underlying neurobehavioral domains may be the most powerful way to detect lead and tobacco effects, because ADHD may represent the tail of a continuum of behavioral effects produced by environmental chemical exposures and other etiologic factors (Mercugliano 1999). However, due to the considerable time and cost involved in the administration of DSM-based diagnostic instruments, previous national estimates of ADHD, such as the present investigation, have relied on medication use or parent report as measures of ADHD status (APA 1994; Lesesne et al. 2003; Olfson 2003; Pastor and Reuben 2002). This study confirms the previously observed association of prenatal ETS exposure and ADHD. We also found a significant dose-response relationship between childhood lead exposure and ADHD. This analysis indicates that 270,000 ADHD cases in children 4-15 years of age are attributable to prenatal ETS exposure, and 290,000 cases of ADHD among U.S. children 4-15 years of age are attributable to environmental lead exposure. The findings of this study underscore the profound behavioral health Behavioral health was first used in the 1980's to name the combination of the fields mental health and substance abuse. As an example, an organization serving both mental health and substance abuse clients might refer to its practice as behavioral health or impact of these prevalent exposures, and highlight the need to strengthen public health efforts to reduce prenatal ETS exposure and childhood lead exposure. REFERENCES APA. 1994. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington DC:American Psychiatric Associations. Bellinger D, Hu H, Titlebaum L, Needleman HL. 1994. Attentional correlates of dentin and bone lead levels in adolescents. 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Blood lead, anemia, and short stature Short stature refers to a height of a human being which is below expected. Shortness is a vague term without a precise definition and with significant relativity to context. are independently associated with cognitive performance in Mexican school children. J Nutr 134(2):363-371. Kotimaa AJ, Moilanen I, Taanila A, Ebeling H, Smalley SL, McGough JJ, et al. 2003. Maternal smoking and hyperactivity in 8-year-old children. J Am Acad Child Adolesc Psychiatry 42(7):826-833. Lanphear BP, Dietrich K, Auinger P, Cox C. 2000. Cognitive deficits associated with blood lead concentrations < 10 microg/dL in US children and adolescents. Public Health Rep 115(6):521-529. Lanphear BP, Hornung R, Khoury J, Yolton K, Baghurst P, Bellinger DC, et al. 2005. Low-level environmental lead exposure and children's intellectual function: an international pooled analysis. Environ Health Perspect 113:894-899. Leech SL, Richardson GA, Goldschmidt L, Day NL. 1999. 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Adult outcome of hyperactive hy·per·ac·tive adj. 1. Highly or excessively active, as a gland. 2. Having behavior characterized by constant overactivity. 3. Afflicted with attention deficit disorder. boys: Educational achievement, occupational rank and psychiatric status. Arch Gen Psychiatry 50:565-576. Mercugliano M. 1999. What is attention-deficit/hyperactivity disorder? Pediatr Clin N Am 46(5):831-843. Mick E, Biederman J, Faraone SV, Sayer J, Kleinman S. 2002a. Case control study of attention deficit disorder and maternal smoking, alcohol use, and drug using during pregnancy. J Am Acad Child Adolesc Psychiatry 41(4):378-384. Mick E, Biederman J, Prince J, Fischer MJ, Faraone SV. 2002b. Impact of low birth weight on attention-deficit hyperactivity disorder Attention-deficit hyperactivity disorder (ADHD) A condition in which a person (usually a child) has an unusually high activity level and a short attention span. People with the disorder may act impulsively and may have learning and behavioral problems. . J Dev Behav Pediatr 2002 23(1):16-22. Milberger S, Biederman J, Faraone SV, Chen L, Jones J. 1996. Is maternal smoking during pregnancy a risk factor for attention deficit hyperactivity disorder in children? Am J Psychiatry 153(9):1138-1142. Milberger S, Biederman J, Faraone SV, Jones J. 1998. Further evidence of an association between maternal smoking during pregnancy and attention deficit hyperactivity disorder: findings from a high-risk sample of siblings. J Clin Child Psychol 27(2):352-358. Miller DT, Paschal DC, Gunter EW, Stroud PE, D'Angelo J. 1987. Determination of blood lead with electrothermal e·lec·tro·ther·mal adj. 1. Of, relating to, or involving both electricity and heat. 2. Of or relating to the production of heat by electricity. atomic absorption using a L'vov platform and matrix modifier (programming) modifier - An operation that alters the state of an object. 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Of or relating to the profession of obstetrics or the care of women during and after pregnancy. obstetrical, obstetric pertaining to or emanating from obstetrics. complications and their association with early onset of illness: a controlled study. BMJ BMJ n abbr (= British Medical Journal) → vom BMA herausgegebene Zeitschrift 305(6864):1256-1259. Olfson M, Gameroff MJ, Marcus SC, Jensen PS. 2003. National trends in the treatment of attention deficit hyperactivity disorder. Am J Psychiatry 160(6):1071-1077. Orlebeke JF, Knol DL, Verhulst FC. 1999. Child behavior problems increased by maternal smoking during pregnancy. Arch Environ Health 54(1):15-19. Parsons PJ, Slavin W. 1993. A rapid Zeeman graphite furnace atomic absorption spectrometric method for the determination of lead in blood. Spectrochimica Acta 48B(6/7):925-939. Pastor PN, Reuben CA. 2002. Attention deficit disorder and learning disability: United States, 1997-98. National Center for Health Statistics. Vital Health Stat 10(206):1-12. Research Triangle Institute. 2004. SUDAAN Language Manual, Release 9.0. Research Triangle Park Research Triangle Park, research, business, medical, and educational complex situated in central North Carolina. It has an area of 6,900 acres (2,795 hectares) and is 8 × 2 mi (13 × 3 km) in size. Named for the triangle formed by Duke Univ. , NC:Research Triangle Institute. Ribary U, Lichtensteiger W. 1989. Effects of acute and chronic prenatal nicotine treatment on central catecholamine catecholamine (kăt'əkôl`əmēn), any of several compounds occurring naturally in the body that serve as hormones or as neutrotransmitters in the sympathetic nervous system. systems of male and female rat fetuses and offspring. J Pharmacol Exp Ther 248(2):786-792. Ris MD, Dietrich KN, Succop PA, Berger OG, Bornschein RL. 2004. Early exposure to lead and neuropsychological neu·ro·psy·chol·o·gy n. The branch of psychology that deals with the relationship between the nervous system, especially the brain, and cerebral or mental functions such as language, memory, and perception. outcome in adolescence. J Int Neuropsychol Soc 10(2):261-270. Rothman KJ. 2002. Epidemiology: An Introduction. New York New York, state, United States New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of :Oxford University Press. Rowland AS, Umbach DM, Stallone L, Naftel AJ, Bohlig EM, Sandler DP. 2002. Prevalence of medication treatment for attention deficit-hyperactivity disorder attention deficit-hyperactivity disorder Attention deficit disorder Psychiatry An inability to control behavior due to difficulty in processing neural stimuli, resulting in ↑ motor activity, ↓ attention span Epidemiology ADHD is the most common among elementary school elementary school: see school. children in Johnston County, North Carolina Johnston County is a county located in the U.S. state of North Carolina. As of 2000, the population was 121,965. Its county seat is Smithfield6. History The county was formed in 1746 from Craven County. . Am J Public Health 92(2):231-244. St Sauver JL, Barbaresi WJ, Katusic SK, Colligan RC, Weaver AL, Jacobsen SJ. 2004. Early life risk factors for attentiondeficit/yperactivity disorder: a population-based cohort study. Mayo Clin Proc 79(9):1124-1131. Sood B, Delaney-Black V, Covington C, Nordstrom-Klee B, Ager J, Templin T, et al. 2001. Prenatal alcohol exposure and childhood behavior at age 6 to 7 years. I. Dose-response effect. Pediatrics 108(2):e34. Thapar A, Fowler T, Rice F, Scourfield J, van den Bree M, Thomas H, et al. 2003. Maternal smoking during pregnancy and attention deficit hyperactivity disorder symptoms in offspring. Am J Psychiatry 160(11):1985-1989. Wasserman GA, Liu X, Pine D, Graziano JH. 2001. Contribution of maternal smoking during pregnancy and lead exposure to early child behavior problems. Neurotoxicol Teratol 23:13-21. Wasserman GA, Staghezza-Jaramillo B, Shrout P, Popovac D, Graziano J. 1998. The effect of lead exposure on behavior problems in preschool children. Am J Public Health 88(3):481-486. Weissman MM, Warner V, Wickramaratne PJ, Kandel DB. 1999. Maternal smoking during pregnancy and psychopathology in offspring followed to adulthood. J Am Acad Child Adolesc Psychiatry 38(7):892-899. Weitzman M, Gortmaker S, Sobol A. 1992. Maternal smoking and behavior problems of children. Pediatrics 90(3):342-349. Williams GM, O'Callaghan M, Najman JM, Bor W, Andersen MJ, Richards D, et al. 1998. Maternal cigarette smoking and child psychiatric morbidity: a longitudinal study longitudinal study a chronological study in epidemiology which attempts to establish a relationship between an antecedent cause and a subsequent effect. See also cohort study. . Pediatrics 102(1):e11. Wolraich ML, Hannah JN, Pinnock TY, Baumgaertel A, Brown J. 1996. Comparison of diagnostic criteria for attention-deficit hyperactivity disorder in a county-wide sample. J Am Acad Child Adolesc Psychiatry 35(3):319-324. Joe M. Braun, (1) Robert S. Kahn, (2,3) Tanya Froehlich, (3,4) Peggy Auinger, (5) and Bruce P. Lanphear (2,3) (1) College of Nursing, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin For other places with the same name, see Milwaukee (disambiguation). Milwaukee is the largest city within the state of Wisconsin and 25th largest (by population) in the United States. , USA; (2) Division of General and Community Pediatrics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio “Cincinnati” redirects here. For other uses, see Cincinnati (disambiguation). Cincinnati is a city in the U.S. state of Ohio and the county seat of Hamilton County. , USA; (3) Cincinnati Children's Environmental Health Center, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; (4) Division of Developmental Behavioral Pediatrics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; (5) Department of Pediatrics, University of Rochester The University of Rochester (UR) is a private, coeducational and nonsectarian research university located in Rochester, New York. The university is one of 62 elected members of the Association of American Universities. School of Medicine, Rochester, New York This article is about the city of Rochester in Monroe County. For the town in Ulster County, see Rochester, Ulster County, New York. Rochester, once known as The Flour City, and more recently as The Flower City or , USA Address correspondence to B.P. Lanphear, Mail location 7035, 2800 Winslow Ave., Cincinnati OH 45206 USA. Telephone: (513) 636-3778. Fax: (513) 636-4402. E-mail: bruce.lanphear@cchmc.org This research was supported by grants from the National Institute of Child Health and Human Development HD40362 (R.S.K.), HD41141 (R.S.K.), National Research Service Award 1T32PE10027 (T.F.), National Institutes of Health and U.S. Environmental Protection Agency Environmental Protection Agency (EPA), independent agency of the U.S. government, with headquarters in Washington, D.C. It was established in 1970 to reduce and control air and water pollution, noise pollution, and radiation and to ensure the safe handling and PO1-ES11261 (B.P.L.). The authors declare they have no competing financial interests. Received 1 July 2006; accepted 18 September 2006.
Table 1. Prevalence of stimulant medication use and parent-reported ADHD
among children 4-15 years of age in NHANES 1999-2002 according to
demographic and medical factors.
Weighted
percent of
parent-
reported
ADHA with
prescription
Sample stimulant p-
Variable size (n) use (95% CI) Value (a)
Total 4,704 4.2(3.3-5.3)
Age (years) <0.001
4-6 1,018 1.0(0.4-2.4)
7-9 1,003 4.8(3.3-7.0)
10-12 1,182 6.5(4.5-9.2)
13-15 1,501 4.5(2.4-8.2)
Sex <0.001
Male 2,264 6.6(5.1-8.5)
Female 2,440 1.8(1.2-2.9)
Race 0.001
Mexican American 1,519 1.0(0.6-1.9)
Other Hispanic 218 3.1(1.4-6.8)
Non-Hispanic white 1,293 5.5(4.1-7.2)
Non-Hispanic black 1,493 3.1(2.2-4.4)
Other, including multiracial 181 1.1(0.3-4.1)
PIR 0.639
1st quartile (0-1.04) 1,434 5.7(3.6-8.9)
2nd quartile (1.05-2.08) 1,121 3.6(2.3-5.3)
3rd quartile (2.09-3.73) 916 4.5(2.6-7.7)
4th quartile (3.74-5.0) 789 3.8(2.7-5.5)
Prenatal ETS exposure 0.023
No 4,014 3.4(2.6-4.5)
Yes 616 7.3(4.8-11.2)
Smoker in the home 0.210
No 3,669 3.9(3.0-4.9)
Yes 980 5.6(3.5-9.1)
Lead quintiles ([micro]g/dL) 0.190
1st quintile (ND-0.7) 679 2.1(0.9-4.7)
2nd quintile (0.8-1.0) 795 3.4(1.4-7.7)
3rd quintile (1.1-1.3) 857 5.0(3.6-6.9)
4th quintile (1.4-2.0) 745 4.7(3.1-6.9)
5th quintile ([greater than 995 5.2(2.9-8.9)
or equal to] 2.0)
NICU 0.504
No 4,129 4.0(3.2-5.1)
Yes 532 4.9(2.9-8.2)
Attended preschool 0.003
No 1,518 2.4(1.3-4.5)
Yes 3,178 4.8(3.8-6.1)
Covered by health insurance <0.001
No 630 0.2(0.1-0.9)
Yes 4,011 4.7(3.7-6.0)
Ferritin (ng/mL) 0.107
1st quartile (< 20) 965 2.7(1.3-5.5)
2nd quartile (20-29) 1,073 3.7(2.5-5.5)
3rd quartile (30-42) 955 3.8(2.1-6.9)
4th quartile (> 42) 1,017 7.7(5.2-11.3)
Birth weight 0.905
[greater than or equal to] 2,500g 4,258 4.2(3.3-5.4)
< 2,500g 393 4.0(1.7-9.1)
Cotinine tertiles (imputed) (ng/mL) 0.322
1st tertile (< 0.028) 1,288 3.4(2.4-4.9)
2nd tertile (0.028-0.259) 1,348 4.5(2.7-7.6)
3rd tertile (> 0.260) 1,183 5.8(3.7-9.1)
ND, Not detectable.
(a) Overall p-value for the variable.
Table 2. Logistic regression analysis for parent-reported attention
deficit disorder among children 4-15 years of age, NHANES 1999-2002. (a)
AOR for parent-reported ADHD
with prescription stimulant
Variable use (95% CI) p-Value
Age (years) 1.1 (1.0-1.2) 0.016
Sex
Female Referent
Male 3.7 (2.1-6.6) < 0.001
Race
Non-Hispanic white Referent
Other Hispanic 0.5 (0.1-2.1) 0.322
Mexican American 0.3 (0.1-0.7) 0.005
Non-Hispanic black 0.5 (0.3-0.8) 0.012
Other, including multiracial 0.2 (0.03-1.2) 0.072
Prenatal ETS exposure
No Referent
Yes 2.5 (1.2-5.2) 0.020
Smoker in the home
No Referent
Yes 0.6 (0.3-1.3) 0.224
Lead quintiles ([micro]g/dL)
1st quintile (ND-0.7) Referent
2nd quintile (0.8-1.0) 1.1 (0.4-3.4) 0.804
3rd quintile (1.1-1.3) 2.1 (0.7-6.8) 0.195
4th quintile (1.4-2.0) 2.7 (0.9-8.4) 0.086
5th quintile (> 2.0) 4.1 (1.2-14.0) 0.026
Preschool/child care attendance
No Referent
Yes 2.4 (1.1-5.1) 0.022
Covered by health insurance
No Referent
Yes 18.9 (3.7-97.4) 0.001
Ferritin (ng/mL) 1.006 (0.999-1.013) 0.089
ND, not detectable.
(a) Model adjusted for age, sex, race, prenatal ETS exposure, postnatal
ETS exposure, blood lead levels, preschool or child care attendance,
health insurance coverage, and ferritin levels.
Table 3. Population-attributable fraction of prenatal tobacco exposure
and environmental lead exposure for parent-reported ADHD and stimulant
medication use in children 4-15 years of age, NHANES 1999-2002. (a)
Characteristic Exposed (%) OR (b)
Prenatal ETS exposure 30.7 2.5
Blood lead > 2.0 [micro]g/dL 27.9 4.1
Prenatal ETS exposure or 46.2 3.3
blood lead concentration
> 2.0 [micro]g/dL
Attributable
Characteristic percent (95% CI) Excess cases
Prenatal ETS exposure 18.4(5.1-24.8) 270,000
Blood lead > 2.0 [micro]g/dL 21.1(4.7-25.9) 290,000
Prenatal ETS exposure or 32.2(4.2-41.3) 480,000
blood lead concentration
> 2.0 [micro]g/dL
(a) The risk factors are not mutually exclusive and the estimates of
attributable risk are not additive. All ORs and attributable risks are
adjusted for variables shown in Table 2. (b) Model adjusted for age,
sex, race, prenatal ETS exposure, postnatal ETS exposure, blood lead
levels, preschool or child care attendance, health insurance coverage,
and ferritin levels. Children without routine access to health care were
excluded from the analysis.
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