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      Fetal Lead Exposure at Each Stage of Pregnancy as a Predictor of Infant Mental Development

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          Abstract

          Background

          The impact of prenatal lead exposure on neurodevelopment remains unclear in terms of consistency, the trimester of greatest vulnerability, and the best method for estimating fetal lead exposure.

          Objective

          We studied prenatal lead exposure’s impact on neurodevelopment using repeated measures of fetal dose as reflected by maternal whole blood and plasma lead levels.

          Methods

          We measured lead in maternal plasma and whole blood during each trimester in 146 pregnant women in Mexico City. We then measured umbilical cord blood lead at delivery and, when offspring were 12 and 24 months of age, measured blood lead and administered the Bayley Scales of Infant Development. We used multivariate regression, adjusting for covariates and 24-month blood lead, to compare the impacts of our pregnancy measures of fetal lead dose.

          Results

          Maternal lead levels were moderately high with a first-trimester blood lead mean (± SD) value of 7.1 ± 5.1 μg/dL and 14% of values ≥10 μg/dL. Both maternal plasma and whole blood lead during the first trimester (but not in the second or third trimester) were significant predictors ( p < 0.05) of poorer Mental Development Index (MDI) scores. In models combining all three trimester measures and using standardized coefficients, the effect of first-trimester maternal plasma lead was somewhat greater than the effect of first-trimester maternal whole blood lead and substantially greater than the effects of second- or third-trimester plasma lead, and values averaged over all three trimesters. A 1-SD change in first-trimester plasma lead was associated with a reduction in MDI score of 3.5 points. Postnatal blood lead levels in the offspring were less strongly correlated with MDI scores.

          Conclusions

          Fetal lead exposure has an adverse effect on neurodevelopment, with an effect that may be most pronounced during the first trimester and best captured by measuring lead in either maternal plasma or whole blood.

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          Low-Level Environmental Lead Exposure and Children’s Intellectual Function: An International Pooled Analysis

          Bruce Lanphear, Richard Hornung, Jane Khoury … (2005)
          Lead is a confirmed neurotoxin, but questions remain about lead-associated intellectual deficits at blood lead levels < 10 μg/dL and whether lower exposures are, for a given change in exposure, associated with greater deficits. The objective of this study was to examine the association of intelligence test scores and blood lead concentration, especially for children who had maximal measured blood lead levels < 10 μg/dL. We examined data collected from 1,333 children who participated in seven international population-based longitudinal cohort studies, followed from birth or infancy until 5–10 years of age. The full-scale IQ score was the primary outcome measure. The geometric mean blood lead concentration of the children peaked at 17.8 μg/dL and declined to 9.4 μg/dL by 5–7 years of age; 244 (18%) children had a maximal blood lead concentration < 10 μg/dL, and 103 (8%) had a maximal blood lead concentration < 7.5 μg/dL. After adjustment for covariates, we found an inverse relationship between blood lead concentration and IQ score. Using a log-linear model, we found a 6.9 IQ point decrement [95% confidence interval (CI), 4.2–9.4] associated with an increase in concurrent blood lead levels from 2.4 to 30 μg/dL. The estimated IQ point decrements associated with an increase in blood lead from 2.4 to 10 μg/dL, 10 to 20 μg/dL, and 20 to 30 μg/dL were 3.9 (95% CI, 2.4–5.3), 1.9 (95% CI, 1.2–2.6), and 1.1 (95% CI, 0.7–1.5), respectively. For a given increase in blood lead, the lead-associated intellectual decrement for children with a maximal blood lead level < 7.5 μg/dL was significantly greater than that observed for those with a maximal blood lead level ≥7.5 μg/dL (p = 0.015). We conclude that environmental lead exposure in children who have maximal blood lead levels < 7.5 μg/dL is associated with intellectual deficits.
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            Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter.

            Richard Canfield, Charles R. Henderson, Deborah A. Cory-Slechta … (2003)
            Despite dramatic declines in children's blood lead concentrations and a lowering of the Centers for Disease Control and Prevention's level of concern to 10 microg per deciliter (0.483 micromol per liter), little is known about children's neurobehavioral functioning at lead concentrations below this level. We measured blood lead concentrations in 172 children at 6, 12, 18, 24, 36, 48, and 60 months of age and administered the Stanford-Binet Intelligence Scale at the ages of 3 and 5 years. The relation between IQ and blood lead concentration was estimated with the use of linear and nonlinear mixed models, with adjustment for maternal IQ, quality of the home environment, and other potential confounders. The blood lead concentration was inversely and significantly associated with IQ. In the linear model, each increase of 10 microg per deciliter in the lifetime average blood lead concentration was associated with a 4.6-point decrease in IQ (P=0.004), whereas for the subsample of 101 children whose maximal lead concentrations remained below 10 microg per deciliter, the change in IQ associated with a given change in lead concentration was greater. When estimated in a nonlinear model with the full sample, IQ declined by 7.4 points as lifetime average blood lead concentrations increased from 1 to 10 microg per deciliter. Blood lead concentrations, even those below 10 microg per deciliter, are inversely associated with children's IQ scores at three and five years of age, and associated declines in IQ are greater at these concentrations than at higher concentrations. These findings suggest that more U.S. children may be adversely affected by environmental lead than previously estimated. Copyright 2003 Massachusetts Medical Society
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              Low-level lead exposure and children's IQ: a meta-analysis and search for a threshold.

              Peter J. Schwartz (1994)
              To assess the strength of the association between blood lead and children's IQ, a meta-analysis of the studies examining the relationship in school age children was performed. Emphasis was given to the size of the effect, since that allows comparisons that are informative about potential confounding and effect modifiers. Sensitivity analyses were also performed. A highly significant association was found between lead exposure and children's IQ (P < 0.001). An increase in blood lead from 10 to 20 micrograms/dl was associated with a decrease of 2.6 IQ points in the meta-analysis. This result was robust to inclusion or exclusion of the strongest individual studies and to relaxing the age requirements (school age children) of the meta-analysis. Adding eight studies with effect estimates of 0 would still leave a significant association with blood lead (P < 0.01). There was no evidence that the effect was limited to disadvantaged children and there was a suggestion of the opposite. The studies with mean blood lead levels of 15 micrograms/dl or lower in their sample had higher estimated blood lead slopes, suggesting that a threshold at 10 micrograms/dl is implausible. The study with the lowest mean blood lead level was examined using nonparametric smoothing. It showed no evidence of a threshold down to blood lead concentrations of 1 microgram/dl. Lead interferes with GABAergic and dopaminergic neurotransmission. It has been shown to bind to the NMDA receptor and inhibit long-term potentiation in the hippocampal region of the brain. Moreover, experimental studies have demonstrated that blood levels of 10 micrograms/dl interfere with a broad range of cognitive function in primates. Given this support, these associations in humans should be considered causal.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Environ Health Perspect
                Title: Environmental Health Perspectives
                Publisher: National Institute of Environmental Health Sciences
                ISSN (Print): 0091-6765
                Publication date (Print): November 2006
                Publication date (Electronic): 19 July 2006
                Volume: 114
                Issue: 11
                Pages: 1730-1735
                Affiliations
                [1 ] Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA
                [2 ] Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
                [3 ] Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México
                [4 ] Department of Neurology, Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
                [5 ] Department of Biology and Environmental Toxicology, University of California at Santa Cruz, Santa Cruz, California, USA
                [6 ] Instituto Nacional de Perinatologia, Mexico City, Mexico
                Author notes
                Address correspondence to H. Hu, Department of Environmental Health Sciences, Building 1, Room 6667, University of Michigan School of Public Health, Ann Arbor, MI 48109-2029 USA. Telephone: (734) 764-3188. Fax: (734) 734.936-7283. E-mail: howardhu@ 123456umich.edu

                The authors declare they have no competing financial interests.

                Article
                Publisher ID: ehp0114-001730
                DOI: 10.1289/ehp.9067
                PMC ID: 1665421
                PubMed ID: 17107860
                SO-VID: c9fa5d9b-c565-4dfa-ad2c-2cdc9cebb718
                Copyright © This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI
                History
                Date received : 2 February 2006
                Date accepted : 19 July 2006
                Categories
                Subject: Research
                Subject: Children's Health

                ScienceOpen disciplines: Public health
                Keywords: pregnancy,neurodevelopment,bone,plasma,lead,iq
                Data availability:
                ScienceOpen disciplines: Public health
                Keywords: pregnancy, neurodevelopment, bone, plasma, lead, iq

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