Pre- and postnatal lead effect on head circumference: a case for critical periods

We examined the association of maternal prenatal [range of median blood lead level 7.5-9.0 microg/dl (0.36-0.43 micromol/l) during pregnancy] and child postnatal blood lead level [range of median blood lead level from birth to 48 months 7.0-10.0 microg/dl (0.34-0.48 micromol/l)] with head circumference in from 119 to 199 children from the Mexico City Prospective Lead Study. We used repeated multiple regression modeling with a standard set of control variables, entering blood lead level last. Using Bonferroni-corrected probability values to control for inflation of Type I error due to multiple testing at each age, we found significant negative associations (p<0.05, two-tailed) between 6-month head circumference and 36-week maternal blood lead level, and 36-month head circumference and 12-month blood lead level. Over the 25-75% interquartile range of measured blood lead, head circumference decreased around 0.4 cm. Over the 1-35 microg/dl (0.05-1.68 micromol/l) range of maternal blood lead at 36 weeks, the estimated reduction in 6-month head circumference was 1.9 cm (95% CI = 0.9-3.0 cm). These results suggest that children are more vulnerable to certain effects of lead exposure at specific age ranges, and that the effect of lead on head circumference only becomes evident for brief periods in the first 4 years of life. We discuss various artifacts as well as possible mechanisms by which lead might have produced the observed pattern of results. We suggest that higher lead exposure prevalent several decades ago might have subtly influenced published normative human growth data.