Risk of attention-deficit/hyperactivity disorder and autism spectrum disorder in children associated with gestational levels of toxic metals and essential elements

Abstract

BACKGROUND AND AIM: Intrauterine exposure to toxic metals and deficient/excess levels of essential elements may adversely affect the uniquely sensitive developing human brain and contribute to risk of neurodevelopmental disorders in children. We investigated prenatal levels of toxic metals and essential elements and risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children. METHODS: We included 705 ADHD case, 397 ASD case and 1034 control children and their mothers from the Norwegian Mother, Father and Child Cohort Study (MoBa). Linkage with the Norwegian Patient Registry was used to identify cases. We measured toxic metals and essential elements in maternal whole blood sampled at week 17 of gestation: cadmium; cesium; cobalt; copper; lead; magnesium; manganese; selenium; zinc; total arsenic; and total mercury. Associations between individual metals/elements and odds ratio (OR) of ADHD or ASD diagnoses were investigated using multivariable adjusted logistic regressions with exposures categorized by quartiles (Q1-Q4; Q1 as reference). Also, the exposure-response relationships were examined in restricted cubic splines. RESULTS:Several associations were identified, with many overlapping findings for the two diagnoses. Among the main findings were increased risk of ADHD with both low and high maternal levels of arsenic (nonlinear U-shape) and increased odds of ASD in arsenic Q2 [OR = 1.77 (CI: 1.26, 2.49)]. The highest levels of maternal cadmium were associated with increased risk of ADHD [Q4: OR = 1.59 (CI: 1.15, 2.18) and ASD [Q4: OR = 1.57 (CI: 1.07 2.31]. Increased odds of both diagnoses were observed with the essential elements magnesium [ADHD: Q4: OR = 1.42 (CI: 1.06, 1.91), ASD: nonlinear U-shape] and manganese [ADHD: nonlinear U-shape, ASD: Q4: OR = 1.84 (CI: 1.30, 2.59]. CONCLUSIONS:Although more studies are warranted, our findings suggest that even population levels of these compounds may adversely impact fetal neurodevelopment and constitute common risk factors for both ADHD and ASD. KEYWORDS: toxic metals, essential elements, prenatal exposure, neurodevelopmental disorders