Reduced Intellectual Development in Children with Prenatal Lead Exposure.

Prospective lead studies of child development from the 1980s to date show associations between low blood lead (BPb) concentration and poor neurobehavioral development although the focus of most of these studies has been postnatal exposure. Only some studies included measurement of maternal BPb during pregnancy or at delivery.

A Yugoslavia study used a repeated-measures design and found that increased mid-pregnancy BPb (12–20 weeks) was significantly associated with decreased 3- to 7-year intelligence quotient (IQ) regardless of pattern of postnatal exposure. A Cincinnati, Ohio (USA), study showed lasting significant effects of BPb between 6 and 28 weeks on factor scores representing attention and visuoconstruction in adolescents when prenatal BPb was tested without simultaneously considering postnatal BPb exposure history.

Ideally, we would like to include the entire history of lead exposure in assessing lasting effects of lead on child development. When the study sample is exposed to relatively constant sources of environmental lead, there is often substantial tracking of BPb over time, producing high correlations among serial BPb levels between and within prenatal and postnatal periods. Collinearity among highly correlated BPb variables in the same linear model will produce biased estimates of lead effect with inflated SEs. On the other hand, piecemeal analysis of lead effects, testing one period of lead exposure at a time, ignores potential effects of earlier or later exposure. Such omission could lead to residual confounding of tested lead effects.

The principal lead exposure sources in pregnant women and their children in the Mexico City Prospective Lead Study were air lead and lead from ceramic ware. Air lead decreased continually throughout the 15-year study period because of reduction and elimination of lead in gasoline. Individual exposure to leaded ceramic ware was both idiosyncratic and intermittent. Such variable individual lead exposure substantially reduced BPb tracking in this sample and allowed an analysis of the effect of lead exposure from 12 weeks of pregnancy through the first 10 years of life on child intelligence from 6 to 10 years of age.

Discussion

Increased maternal lead concentration at third trimester of pregnancy, especially around week 28, was associated with decreased intellectual child development, even after controlling for other prenatal and postnatal lead measurements. Other studies found significant adverse associations between postnatal BPb and IQ. In our panel unadjusted regression analyses, we noted a significant effect of 6- to 10-year BPb on child IQ as well, but this effect lost significance when other BPb and covariates were included in mixed-model analysis. Collinearity between prenatal and 6- to 10-year BPb variables was not responsible for loss of explanatory power of 6- to 10-year BPb. Given the modest sample size and relatively low power of this study, we do not claim that lead exposure from 6 to 10 years or any other developmental period has no effect on child IQ. More likely, third-trimester lead exposure is a more powerful predictor of later child IQ and absorbed enough of the variation in IQ formerly attributed to 6- to 10-year BPb to render it insignificant in our model.

In contrast to other studies in which prenatal lead exposure biomarkers were umbilical cord BPb or one or at most two maternal lead measurements during pregnancy, we measured prenatal lead exposure systematically (within an interval of ± 2 weeks) during specific pregnancy stages (weeks 12, 20, 28, and 36 of pregnancy, at delivery, and in umbilical cord). We note that 28-week fetal central nervous system development is distinctly different than development either at 12 weeks or at term. Neuroblast proliferation is essentially complete before 28 weeks, whereas neuronal migration and aggregation continue through the first half of the third trimester. Myelination of tracts within the developing human fetal brain has just begun by 25 weeks. Deeper cortical layers are poorly defined at 24 weeks, clearly developed at 28 weeks, and reach postnatal appearance by 34 weeks of pregnancy. Limiting the range of permitted weeks of pregnancy for placing each maternal BPb in its nominal category probably enhanced our ability to detect pregnancy phase-specific BPb effects.

Other studies did not simultaneously include all lead measurements in their analyses, although one included directional postnatal lead change indicators along with the single pregnancy BPb variable. We were able to include the entire history of lead exposure in our analyses because collinearity among the lead measures was not a significant factor. In our analysis, simultaneous inclusion of 6- to 10-year BPb and the remaining BPb reduced the size of the 6- to 10-year lead coefficient without changing its variance, rendering it insignificant. With the increased power afforded by a larger sample size, 6- to 10-year BPb might well have retained its significance.

Conclusions.

Lead exposure around 28 weeks gestation is a critical period for later child intellectual development, with lasting and possibly permanent effects. There was no evidence of a threshold; the strongest lead effects on IQ occurred within the first few micrograms of BPb.