Commentary: Lead's Latest Cousins: Childhood Central Nervous System Development and the Environment

Brunekreef, Berta,b

doi: 10.1097/EDE.0b013e31823b6398
Child Development
Author Information

From the aInstitute for Risk Assessment Sciences, Universiteit Utrecht, Utrecht, The Netherlands; and bJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.

The author reported no financial interests related to this research.

Correspondence: Bert Brunekreef, Institute for Risk Assessment Sciences, Universiteit Utrecht, PO Box 80178, 3508 TD, Utrecht, The Netherlands. E-mail:

Article Outline

It has been known for decades that lead exposure produces serious effects on the central nervous system of young children.1 Landmark studies such as those conducted by Landrigan et al2 and Needleman3 showed that children with elevated blood- or dentine-lead levels did worse on several neurologic tests. Differences in IQ between high- and low-exposure groups were on the order of 4–8 points in these studies. In retrospect, the blood-lead levels in these studies were extremely high compared with current levels and standards; for example, mean values of 48 μg/dL in the high-exposure group and 27 μg/dL in the “control” group.2 Nowadays, population blood-lead levels in children are an order of magnitude lower, thanks to a series of lead abatement measures, especially the removal of lead from gasoline; but still, at these sharply reduced blood-lead levels, convincing associations between blood lead and various measures of cognitive performance in kids are being observed.4,5

Since the early lead studies, we have seen a steadily growing list of environmental pollutants suspected to adversely affect neurologic development of children, including methyl mercury,6 PCBs,7 dioxins,8 and polybrominated flame retardants.9

Indoor and outdoor air pollution are fresh members of this illustrious club of “lead cousins.” This issue of EPIDEMIOLOGY contains an interesting new contribution of a team of researchers at CREAL that has been very active in this field during the past several years.1016 In their latest study, Vrijheid et al17 document prospectively an association between gas cooking and cognitive performance in preschool children. Children in a birth cohort in 4 regions in Spain were tested for mental development between the ages of 11 and 22 months. Gas cooking was reported in about 40% of participating families and was associated with a decrease of about 2.5 points on the Bayley Scale of Infant Development. This difference represents about one-sixth of the standard deviation of the score observed in this population, which presumably prompted the investigators to label the effect as “small” in their conclusions. They also considered it to be “adverse” and “detrimental,” which perhaps requires a bit more discussion than the authors devote to these terms in their paper. They argue only that the public health implications could be substantial because “neurodevelopmental disorders and disabilities carry a high social and economic burden.” That may very well be true, but it is still a leap from a 2.5-point population average difference in the Bayley mental development score measured between the ages of 11 and 22 months to “disorders and disabilities.” More discussion and probably research into the long-term consequences of having a somewhat lower score on these and other neurodevelopmental scales seem necessary. The Bayley assessment is widely used in studies of early neurodevelopment, but some studies suggest that its prognostic value for neurodevelopment at school age or even in the first 3 years of life may be limited.1821 Also, more work seems to be needed to identify the effect of environmental risk factors on the proportion of children having a neurodevelopment score below some critical value. In the literature on neurologic effects of childhood lead exposure, the point has been forcefully made that a modest group mean effect on IQ may markedly increase the proportion of children needing special education at the lower end of the range and conversely may noticeably decrease the proportion of highly intelligent children our highly complex society may need in the future to deal with all sorts of challenges.22

Another thing the lead story has taught us is that adverse neurologic effects of lead in children have not disappeared, unfortunately, with the massive decline in blood-lead levels observed over the past decades.22 That raises an interesting question for the current studies on environmental effects on child neurodevelopment, such as the CREAL study of gas cooking,17 whereas the authors have been very careful to evaluate a long list of potential confounders; lead was not among them. This is more generally true of many recent studies in this area. There is no a priori reason to expect a confounding role of lead in studies of gas cooking, etc, but no such reason is required, given the primacy of lead among the environmental risk factors for childhood neurologic damage.

Finally, as with any emerging issue in epidemiology, we need to be aware that initial positive findings of an association may not survive systematic attempts at replication. The CREAL team is already leading a major effort in Europe to jointly analyze a series of birth cohorts for associations between outdoor air pollution and neurodevelopment in children ( It has also recently spearheaded an inventory of birth cohorts that have environmental exposures (,23 which has identified more than 15 cohorts with data on neurodevelopment, many of which have data on gas cooking. Thus, the foundation has already been laid. It is now a matter of finding the time and resources to do the meta-analysis that the paper17 published in this issue of EPIDEMIOLOGY calls for.

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BERT BRUNEKREEF is a professor of environmental epidemiology at the University of Utrecht, The Netherlands. He has been active in exposure assessment and studying health effects of indoor and outdoor pollution in national and international studies. Currently, he is coordinating the European Study of Cohorts for Air Pollution Effects (ESCAPE), a Europe-wide effort to assess long-term effects of air pollution in over 30 existing cohort studies. He serves on the Health Effects Institute Review Committee as well.

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1. Carlisle JC, Dowling KC, Siegel DM, Alexeeff GV. A blood lead benchmark for assessing risks from childhood lead exposure. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2009;44:1200–1208.
2. Landrigan PJ, Whitworth RH, Baloh RW, Staehling NW, Barthel WF, Rosenblum BF. Neuropsychological dysfunction in children with chronic low-level lead absorption. Lancet. 1975;1:708–712.
3. Needleman HL. Lead levels and children's psychologic performance. N Engl J Med. 1979;301:163.
4. Jusko TA, Henderson CR, Lanphear BP, Cory-Slechta DA, Parsons PJ, Canfield RL. Blood lead concentrations <10 microg/dL and child intelligence at 6 years of age. Environ Health Perspect. 2008;116:243–248.
5. Jedrychowski W, Perera FP, Jankowski J. Very low prenatal exposure to lead and mental development of children in infancy and early childhood: Krakow prospective cohort study. Neuroepidemiology. 2009;32:270–278.
6. Grandjean P, Weihe P, White RF. Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury. Neurotoxicol Teratol. 1997;19:417–428.
7. Newman J, Aucompaugh AG, Schell LM. PCBs and cognitive functioning of Mohawk adolescents. Neurotoxicol Teratol. 2006;28:439–445.
8. Patandin S, Lanting CI, Mulder PG, Boersma ER, Sauer PJ, Weisglas-Kuperus N. Effects of environmental exposure to polychlorinated biphenyls and dioxins on cognitive abilities in Dutch children at 42 months of age. J Pediatr. 1999;134:33–41.
9. Roze E, Meijer L, Bakker A, Van Braeckel KN, Sauer PJ, Bos AF. Prenatal exposure to organohalogens, including brominated flame retardants, influences motor, cognitive, and behavioral performance at school age. Environ Health Perspect. 2009;117:1953–1958.
10. Julvez J, Ribas-Fito N, Torrent M, Forns M, Garcia-Esteban R, Sunyer J. Maternal smoking habits and cognitive development of children at age 4 years in a population-based birth cohort. Int J Epidemiol. 2007;36:825–832.
11. Guxens M, Aguilera I, Ballester F, et al.. Prenatal exposure to residential air pollution and infant mental development: modulation by antioxidants and detoxification factors. Environ Health Perspect. In press.
12. Morales E, Julvez J, Torrent M. Association of early-life exposure to household gas appliances and indoor nitrogen dioxide with cognition and attention behavior in preschoolers. Am J Epidemiol. 2009;169:1327–1336.
13. Morales E, Sunyer J, Julvez J. GSTM1 polymorphisms modify the effect of maternal smoking during pregnancy on cognitive functioning in preschoolers. Int J Epidemiol. 2009;38:690–697.
14. Julvez J, Fortuny J, Mendez M, Torrent M, Ribas-Fito N, Sunyer J. Maternal use of folic acid supplements during pregnancy and four-year-old neurodevelopment in a population-based birth cohort. Paediatr Perinat Epidemiol. 2009;23:199–206.
15. Freire C, Ramos R, Puertas R. Association of traffic-related air pollution with cognitive development in children. J Epidemiol Community Health. 2010;64:223–228.
16. Gascon M, Vrijheid M, Martinez D. Effects of pre and postnatal exposure to low levels of polybromodiphenyl ethers on neurodevelopment and thyroid hormone levels at 4 years of age. Environ Int. 2011;37:605–611.
17. Vrijheid M, Martinez D, Aguilera I, et al.. Indoor air pollution from gas cooking and infant neurodevelopment. Epidemiology. 2012;23:23–32.
18. McGrath E, Wypij D, Rappaport LA, Newburger JW, Bellinger DC. Prediction of IQ and achievement at age 8 years from neurodevelopmental status at age 1 year in children with D-transposition of the great arteries. Pediatrics. 2004;114:e572–e576.
19. Roze E, Meijer L, Van Braeckel KN, Ruiter SA, Bruggink JL, Bos AF. Developmental trajectories from birth to school age in healthy term-born children. Pediatrics. 2010;126:e1134–e1142.
20. Hack M, Taylor HG, Drotar D. Poor predictive validity of the Bayley scales of infant development for cognitive function of extremely low birth weight children at school age. Pediatrics. 2005;116:333–341.
21. Lung FW, Shu BC, Chiang TL, Chen PF, Lin LL. Predictive validity of Bayley scale in language development of children at 6–36 months. Pediatr Int. 2009;51:666–669.
22. Bellinger DC. The protean toxicities of lead: new chapters in a familiar story. Int J Environ Res Public Health. 2011;8:2593–2628.
23. Vrijheid M, Casas M, Bergstrom A, et al.. European birth cohorts for environmental health research. Environ Health Perspect. In press.
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