Exposure to lead on children's intellectual functioning: A target trial with multimedia biomarkers in Mexico City

Lead exposure is neurotoxic during pregnancy and early childhood. Quantifying the expected effects of potential lead reductions on neurologic outcomes is valuable for decision makers. We estimated associations between integrated lead levels during pregnancy and early childhood on children's intellectual performance framed as hypothetical interventions to decrease lead levels. Our data source was the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) longitudinal birth cohort in Mexico City. Data included information on multiple biomarkers in the pre-and postnatal periods. We assessed the child's intellectual functioning at 48 months of age with McCarthy Scales of Children's Abilities including specific domains and the composite of these scales called the General Cognitive Index (GCI). We generated multi-media biomarkers (MMBs) combining lead biomarkers across biologic matrix and developmental period, using Weighted Quantile Sum Regression (WQS), and g-computation to estimate mean differences in cognitive scores (95%CIs) under hypothetical lead-reduction interventions. We estimated a mean difference of 0.60 points [95%CI: -0.25, 1.46] for the GCI and 0.77 [95%CI: 0.24, 1.30] for the perceptual scale following a 40% hypothetical reduction. When examined separately, prenatal exposure showed the strongest association with the perceptual domain and postnatal exposure with the quantitative domain. A sensitivity analysis using principal component analysis, agnostic to exposure directionality, yielded mostly null but directionally inconsistent results. Our results suggest that potentially 40% reductions of lead levels during pregnancy and early childhood in Mexico City may be associated with modest improvements in specific cognitive domains, although results were sensitive to the method used to construct MMBs.