Environmental Exposures and ADHD
Environ Health Perspect 115:395-399 (2007). doi:10.1289/ehp.10274 available via http://dx.doi.org [Online 24 June 2007]
Referencing: Exposures to Environmental Toxicants and Attention Deficit Hyperactivity Disorder in U.S. Children
In their article, "Exposures to Environmental Toxicants and Attention Deficit Hyperactivity Disorder [ADHD] in U.S. Children," Braun et al. (2006) advanced our knowledge of the effects of environmental tobacco smoke (ETS) and lead on the central nervous system of children. With respect to lead exposure, the study, importantly, focused on an older age group (4–15 years) than is generally studied (< 6 years) because of the greater sensitivity of the developing central nervous system to environmental insult early in life [Centers for Disease Control and Prevention (CDC) 1997].
In the logistic model used by Braun et al. (2006), the association of ADHD with lead exposure was statistically significant in the highest exposure quintile; however, it was also tenuous. Although not unheard of, the cutoff (p < 0.2) for inclusion of factors and variables associated with ADHD on univariate analysis was generous compared with the commonly used 0.1 or 0.05, and very close to the p-value of the lead–ADHD association of 0.19. The lead–ADHD relationship also exhibited a significant monotonic dose response, so it would have been helpful to know how the authors developed their exposure metric. Why, for example, were quintiles selected rather than another interval scheme, and why were they not of uniform size? Was the reported dose response the only model considered, or did the authors investigate other models, as some have done in studying the relationship of lead exposure and cognition (Canfield et al. 2003)?
Braun et al. (2006) noted that their analyses were limited by the cross-sectional nature of the National Health and Nutrition Examination Survey data they used, precluding adjustment of their model for certain covariates and potential confounders (e.g., parental psychopathology). Based on data from multiple studies, ADHD heritability has been estimated to be about 75% (Biederman and Faraone 2005). Inability to adjust for parental psychopathology is therefore an important limitation, because adjustment would likely reduce—and might eliminate—the associations of ADHD with ETS and lead. In studies of lead exposure and cognition, some of which Braun et al. (2006) cited as being consistent with their findings, the strength of the IQ–lead relationship can be dwarfed by the relationship of IQ to other factors such as parenting and socioeconomic status (Koller et al. 2004). When reporting associations of environmental contaminants and pathology, it seems prudent to maintain a broader perspective, as well as an environmental health perspective.
The authors declare they have no competing financial interests.
Jack Brondum
Hennepin County Department of
Human Services and Public Health
Environmental Health and Epidemiology
Hopkins, Minnesota
References
Biederman J, Faraone SV. 2005. Attention-deficit hyperactivity disorder. Lancet 366: 237–248.
Braun JM, Kahn RS, Froehlich T, Auinger P, Lanphear BP. 2006. Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children. Environ Health Perspect 114:1904–1909.
Canfield RL, Henderson CR Jr, Cory-Schlechta DA, Cox C, Jusko TA, Lanphear BP. 2003. Intellectual impairment in children with blood lead concentrations below 10 µg per deciliter. N Engl J Med 348:1517–1526.
CDC. 1997. Screening Young Children for Lead Poisoning: Guidance for State and Local Public Health Officials. Atlanta, GA:Centers for Disease Control and Prevention.
Koller K, Brown T, Spurgeon, Levy L. 2004. Recent developments in low-level lead exposure and intellectual impairment in children. Environ Health Perspect 112: 987–994.
ADHD: Braun et al. Respond
Environ Health Perspect 115:395-399 (2007). doi:10.1289/ehp.10274R available via http://dx.doi.org [Online 24 June 2007]
We appreciate the comments of Brondum, and Konofal and Cortese, and the opportunity to clarify our results (Braun et al. 2006). It is common practice to select variables with a p-value of 0.2 for inclusion in multivariable models (Katz 1999). Although the association of blood lead levels and ADHD appeared "tenuous" in bivariate analysis (i.e., p = 0.19), this was largely an artifact of our decision to categorize blood lead levels. When we entered lead into our multivariable analysis as a continuous variable, we found a 1.2-fold increased odds [95% confidence interval (CI), 1.0–1.4; p = 0.02] of ADHD for each 1.0-µg/dL increase in blood lead levels. The blood lead quintiles were not divided into exactly equal sample sizes because we used weighted percentages to categorize the data. We decided a priori to present the analysis in quintiles to make the results easier to interpret and also to illustrate any dose–response relationships for blood lead levels and ADHD.
As we noted in the "Discussion" of our article (Braun et al. 2006), a limitation of our study was the inability to adjust for parental psychopathology. This is an unfortunate trade-off when using a large nationally representative survey. In other studies, prenatal tobacco exposure has been shown to be a risk factor for the development of ADHD after controlling for parental psychopathology (Mick et al. 2002; Weissman et al. 1999). Although there is considerable experimental and epidemiologic evidence linking lead exposure with behaviors consistent with ADHD, future studies of childhood lead exposure will need to confirm our results by accounting for parental psychopathology and other potential confounders.
The hypothesis proposed by Konofal and Cortese—that iron deficiency may play a role in symptom severity among children with ADHD—is intriguing. Indeed, it was their original research that prompted us to incorporate ferritin as a measure of iron status (Konofal et al. 2004). It is certainly plausible that iron deficiency may confound or modify the effects of environmental lead exposure on ADHD in children. Alternatively, lead exposure may act as a confounder or modifier for the observed effects of iron deficiency with ADHD. Unfortunately, we were not able to examine whether ferritin (or other indicators of iron status) was associated with ADHD symptom severity using the National Health and Nutrition Examination Survey. Nor did we specifically test for an association between iron deficiency and ADHD. Although iron or other micronutrient supplementation may protect children from lead toxicity, recent evidence from a double-blind randomized trial (Kordas et al. 2005) suggests that iron and zinc supplementation did not appreciably lower blood lead levels or improve child behavior, as measured by the Conners Rating Scales. However, Kordas et al. included only children without anemia in their trial.
The authors declare they have no competing financial interests.
Joe M. Braun
Department of Epidemiology
University of North Carolina-Chapel Hill
Chapel Hill, North Carolina
Bruce P. Lanphear
Robert S. Kahn
Tanya Froehlich
Department of Pediatrics
Peggy Auinger
Department of Pediatrics
University of Rochester School of Medicine
Rochester, New York
References
Braun JM, Froehlich TF, Kahn RS, Auinger P, Lanphear BP. 2006. Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children. Environ Health Perspect 114:1904–1909.
Katz M. 1999. Multivariable Analysis: A Practical Guide for Clinicians. New York:Cambridge University Press.
Konofal E, Lecendreux M, Arnulf I, Mouren M. 2004. Iron deficiency in children with attention-deficit/hyperactivity disorder. Arch Pediatr Adolesc Med 158:1113–1115.
Kordas K, Stoltzfus RJ, Lopez P, Rico JA, Rosado JL. 2005. Iron and zinc supplementation does not improve parent or teacher ratings of behavior in first grade Mexican children exposed to lead. J Pediatr 147:632–639.
Mick E, Biederman J, Faraone SV, Sayer J, Kleinman S. 2002. Case-control study of attention-deficit hyperactivity disorder and maternal smoking, alcohol use, and drug use during pregnancy. J Am Acad Child Adolesc Psychiatry 41:378–385.
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 38:892–899.