Testing the Dose–Response Specification in Epidemiology: Public Health and Policy Consequences for Lead
Open accessAbstract
Statistical evaluation of the dose–response function in lead epidemiology is rarely attempted. Economic evaluation of health benefits of lead reduction usually assumes a linear dose–response function, regardless of the outcome measure used. We reanalyzed a previously published study, an international pooled data set combining data from seven prospective lead studies examining contemporaneous blood lead effect on IQ (intelligence quotient) of 7-year-old children (n = 1,333). We constructed alternative linear multiple regression models with linear blood lead terms (linear–linear dose response) and natural-log–transformed blood lead terms (log-linear dose response). We tested the two lead specifications for nonlinearity in the models, compared the two lead specifications for significantly better fit to the data, and examined the effects of possible residual confounding on the functional form of the dose–response relationship. We found that a log-linear lead–IQ relationship was a significantly better fit than was a linear–linear relationship for IQ (p = 0.009), with little evidence of residual confounding of included model variables. We substituted the log-linear lead–IQ effect in a previously published health benefits model and found that the economic savings due to U.S. population lead decrease between 1976 and 1999 (from 17.1 μg/dL to 2.0 μg/dL) was 2.2 times ($319 billion) that calculated using a linear–linear dose–response function ($149 billion). The Centers for Disease Control and Prevention action limit of 10 μg/dL for children fails to protect against most damage and economic cost attributable to lead exposure.
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A meta-analysis of eight epidemiological studies reported that adding more family controls to a relatively parsimonious set did little to alter the relationship between lead and IQ in children.
“This finding is consistent with a meta-analysis of eight studies conducted by epidemiologists in which they reported that adding more family controls to a relatively parsimonious set (maternal schooling and IQ, the HOME score, birth weight, and city) did little to alter the relationship between lead and IQ in children (Rothenberg and Rothenberg 2005).”
From Do Low Levels of Blood Lead Reduce Children's Future Test Scores? (2018) · cites this paper as Rothenberg and Rothenberg 2005
The Materials and Methods (Data sets; page unavailable) says that additional control variables did not significantly alter the child IQ–lead relationship. It also says that seven of eight eligible studies contributed to the pooled analysis, not that a meta-analysis included eight studies. (LLM, conf=0.90)
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Lanphear, B. P., Hornung, R., Khoury, J., Yolton, K., Baghurst, P., Bellinger, D. C., Canfield, R. L., Dietrich, K. N., Bornschein, R., Greene, T., et al. (2005) · Environmental Health Perspectives · doi:10.1289/ehp.7688 · Cited by 2,205 · see citing works
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- Baghurst PA McMichael AJ Wigg NR Vimpani GV Robertson EF Roberts RJ 1992 Environmental exposure to lead and children’s intelligence at the age of seven years. The Port Pirie Cohort Study N Engl J Med 327 18 1279 1284 1383818
- Becher H 1992 The concept of residual confounding in regression models and some applications Stat Med 11 1747 1757 1485057
- Bellinger DC Stiles KM Needleman HL 1992 Low-level lead exposure, intelligence and academic achievement: a long-term follow-up study Pediatrics 90 6 855 861 1437425
- Benedetti A Abrahamowicz M 2004 Using generalized additive models to reduce residual confounding Stat Med 23 3781 3801 15580601
- Canfield RL Henderson CR Jr Cory-Slechta DA Cox C Jusko TA Lanphear BP 2003 Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter N Engl J Med 348 16 1517 1526 12700371 PMC4046839
- Dietrich KN Berger OG Succop PA Hammond PB Bornschein RL 1993 The developmental consequences of low to moderate prenatal and postnatal lead exposure: intellectual attainment in the Cincinnati Lead Study Cohort following school entry Neurotoxicol Teratol 15 1 37 44 8459787
- Ernhart CB Morrow-Tlucak M Wolf AW Super D Drotar D 1989 Low level lead exposure in the prenatal and early preschool periods: intelligence prior to school entry Neurotoxicol Teratol 11 2 161 170 2733654
- Grosse SD Matte TD Schwartz J Jackson RJ 2002 Economic gains resulting from the reduction in children’s exposure to lead in the United States Environ Health Perspect 110 563 569 12055046 PMC1240871
- Mielke HW Anderson JC Berry KJ Mielke PW Chaney RL Leech M 1983 Lead concentrations in inner-city soils as a factor in the child lead problem Am J Public Health 73 12 1366 1369 6638229 PMC1651267
- Mielke HW Dugas D Mielke PW Jr Smith KS Gonzales CR 1997 Associations between soil lead and childhood blood lead in urban New Orleans and rural Lafourche Parish of Louisiana Environ Health Perspect 105 950 954 9300928 PMC1470368
- Mielke HW Gonzales CR Smith MK Mielke PW 1999 The urban environment and children’s health: soils as an integrator of lead, zinc, and cadmium in New Orleans, Louisiana, U.S.A Environ Res 81 2 117 129 10433843
- Nawrot TS Thijs L Den Hond EM Roels HA Staessen JA 2002 An epidemiological re-appraisal of the association between blood pressure and blood lead: a meta-analysis J Hum Hypertens 16 2 123 131 11850770
- Pacala SW Bulte E List JA Levin SA 2003 False alarm over environmental false alarms Science 301 1187 1188 12947184
- Schnaas L Rothenberg SJ Perroni E Martinez S Hernandez C Hernandez RM 2000 Temporal pattern in the effect of postnatal blood lead level on intellectual development of young children Neurotoxicol Teratol 22 6 805 810 11120385
- Schwartz J 1994 Low-level lead exposure and children’s IQ: a meta-analysis and search for a threshold Environ Res 65 1 42 55 8162884
- Wasserman GA Liu X Lolacono NJ Factor-Litvak P Kline JK Popovac D 1997 Lead exposure and intelligence in 7-year-old children: the Yugoslavia Prospective Study Environ Health Perspect 105 956 962 9410739 PMC1470353
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Rauh, V., Arunajadai, S., Horton, M., Perera, F., Hoepner, L., Barr, D. B., & Whyatt, R. (2011) · Environmental Health Perspectives · doi:10.1289/ehp.1003160 · Cited by 524 · see citing works
“In light of experimental evidence suggesting that CPF effects in rodents may be irreversible (Slotkin 2005), it will be important to determine how any neurocognitive deficits associated with prenatal CPF exposure might respond to treatment or early intervention.”
BackgroundDo Low Levels of Blood Lead Reduce Children's Future Test Scores?
Aizer, A., Currie, J., Simon, P., & Vivier, P. (2018) · American Economic Journal: Applied Economics · doi:10.1257/app.20160404 · Cited by 114 · see citing works
- Authors
- Rothenberg, S. J., & Rothenberg, J. C.
- Affiliations
- Instituto Nacional de Salud Pública (MX)
- The University of Sydney (AU)
- Venue
- Environmental Health Perspectives
- Publisher
- American Chemical Society (ACS)
- Published
- 2005-05-10
- Volume
- 113
- Issue
- 9
- Pages
- 1190-1195
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- PMC
- PMC1280400
- OpenAlex
- W2102440076
- Cited by
- 63
- References
- 1
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 1 · 2022: 5 · 2020: 2 · 2018: 3 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 5 · 2013: 3 · 2012: 3
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- creativecommons.org/licenses/by/4.0/ (vor, 4616 d)
- Locations
- Environmental Health Perspectives (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- U.S. Environmental Protection Agency
- Consejo Nacional de Ciencia y Tecnología
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
- Physical Sciences › Environmental Science › Pollution › Heavy metals in environment
- Keywords
- lead exposure, blood lead levels, dose-response relationship, dose-response linearity, child IQ, residual confounding
- MeSH terms
- Child, Child, Preschool, Cognition Disorders, Cost-Benefit Analysis, Dose-Response Relationship, Drug, Environmental Exposure, Humans, Infant, Intelligence, Lead, Prospective Studies, Regression Analysis, Models, Statistical, Confounding Factors, Epidemiologic
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