Dentine biomarkers of prenatal and early childhood exposure to manganese, zinc and lead and childhood behavior

Abstract

Background: Metal exposure alters neurodevelopmental outcomes; little is known about critical windows of susceptibility when exposure exerts the strongest effect.

Objective: To examine associations between dentine biomarkers of manganese (Mn), zinc (Zn) and lead (Pb) and later childhood behaviors.

Methods: Subjects enrolled in a longitudinal birth cohort study in Mexico City provided naturally shed deciduous teeth. We estimated weekly prenatal and postnatal dentine Mn, Zn and Pb concentrations in teeth using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) and measured behavior at ages 8-11 years of age using the Behavior Assessment System for Children, 2nd edition (BASC-2). We used distributed lag models and lagged weighted quantile sum regression to identify the role of individual and combined dentine biomarkers of Mn, Zn and Pb on behavioral outcomes controlling for maternal education and gestational age.

Results: Among the 133 subjects included in this study, prenatal and early postnatal dentine Mn appeared protective against childhood behavioral problems, specifically hyperactivity and attention. Postnatal dentine Mn was associated with increased reporting of internalizing problems, specifically anxiety. At 6 months, a 1-unit increase (unit = 1 SD of log concentration) in Mn was associated with a 0.18-unit (unit = 1 SD of BASC-2 score) increase in internalizing symptoms score and a 0.25-unit increase in anxiety. Postnatal Pb was associated with increasing anxiety symptoms; at 12 months, a 1-unit increase in Pb was associated with a 0.4 unit increase in anxiety symptoms. When examined as a metal mixture, we observed two potential windows of susceptibility to increased anxiety symptoms: the first window (0-8 months) appeared driven by Mn, the second window (8-12 months) was driven by the metal mixture and dominated by Pb. A 1-unit increase in the mixture index was associated with a 0.7-unit increase in SD of anxiety symptoms.

Conclusions: Childhood behaviors may demonstrate postnatal windows of susceptibility to individual and mixed metal concentrations measured in deciduous teeth. Prenatal dentine Mn may be protective, while excessive early postnatal Mn may increase risk for adverse behaviors. In combination, higher concentrations of Mn, Zn and Pb may have an adverse impact on behavior.

Keywords: Anxiety; Child behavior; Dentine biomarkers; Manganese; Metal mixtures.

Figure 1.

Tooth metal levels from early second trimester (−5 months before birth) to one year of age (12 months) for (A) Mn as ln ⁵⁵Mn:⁴²Ca ratio, (B) Zn as ⁶⁶Zn:⁴²Ca ratio and (C) Pb as ²⁰⁸Pb:⁴²Ca ration. Dots (dark blue = male, light blue = female) represent individual tooth measurements for 133 participants with approximately 50 measurements per participant. Line represents Loess smoother.

Figure 2.

Individual Reversed DLM plots demonstrating association between fine scale resolution dentine metal levels and BASC-2 Behavioral Symptoms; [(A) manganese (top), (B) zinc(middle), (C)lead (bottom)] adjusted for maternal education and gestational age (n = 133); Y axis = time varying correlation between exposure and outcome; X axis = time since birth representing timing of tooth sampling; central black line indicates = correlation; blue band represents the 95% confidence intervals and the vertical bars represent the 95% Holms-Bonferroni family-wise confidence intervals. A significant association indicating a critical window is defined as an area of the rDLM that does not include zero.

Figure 3.

Lagged WQS representing time varying associations of co-exposure to dentine Mn, Zn and Pb with BASC-2 Behavioral Skills Index, Internalizing Symptoms, and Anxiety Symptoms assessed at 8–11 years of age among 133 ELEMENT subjects. (A) Lagged WQS plots with 95% piecewise confidence intervals (blue band) and 95% Holm-Bonferonni family-wise confidence intervals (vertical bars). The Yaxis represents time varying correlation between joint exposure and outcome. (B) Weighted associations of the individual metals to the observed mixture effects shown in plot A. In both figures, the X-axis represents the time since birth indicating the timing (in months) of tooth sampling.