Sexually dimorphic associations between prenatal blood lead exposure and temporal processing in 6- to 7-year-old children in Mexico City

Abstract

BACKGROUND AND AIM: Temporal-Response Differentiation (TRD) is an operant testing procedure to assess time perception. Few human studies have assessed whether lead (Pb) affects temporal processing. METHODS: As part of a prospective cohort study in Mexico, 547 six- to seven-year-old children completed a TRD task to assess temporal processing. Pb was measured in maternal blood collected during the second trimester (2T), third trimester (3T), and on the day of delivery; and, in infant’s umbilical cord (CB) at delivery. During the TRD task, children repeatedly held a lever down for 10-14 seconds to receive a reward. We examined the frequency, average duration, and standard deviation of timing holds. General linear models were used to examine associations between each Pb measure and each outcome adjusted for child’s age at testing, maternal education, and socioeconomic status. Sexually dimorphic effects were evaluated using 2-way interactions between child sex and exposure. RESULTS:In the number of holds models, there was a significant interaction between CB lead levels and sex (β=1.5; 95%CI: 0.12, 2.9) with boys having a reduced number of holds with higher Pb than girls. In the average duration of holds models, there were significant interactions of 3T and delivery Pb with sex (β=-0.72; 95%CI: -1.33, -0.12 and β=-0.59; 95%CI: -1.1, -0.1, respectively) with males having longer durations with higher Pb than girls. In the standard deviation of hold durations models, there were significant interactions of 3T, delivery, and CB Pb with sex (β=-0.79; 95%CI: -1.3, -0.23, β=-0.78; 95%CI: -1.2, -0.3, and β=-1.1; 95%CI: -1.7, -0.4, respectively) with boys having greater variability in their hold durations with higher exposure than girls. CONCLUSIONS:Our results offer new insights into the cognitive mechanisms involved in prenatal Pb-related neurodevelopmental deficits, implicating temporal processing mechanisms, and provide a new approach to evaluate sex-specific effects of lead exposure. KEYWORDS: Heavy metals, Neurodevelopmental outcomes, Children's environmental health