Abstract
BackgroundPrenatal exposure to toxic metals or variations in maternal levels of essential elements during pregnancy may be a risk factor for neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in offspring. ObjectivesWe investigated whether maternal levels of toxic metals and essential elements measured in mid-pregnancy, individually and as mixtures, were associated with childhood diagnosis of ADHD or ASD. MethodsThis study is based on the Norwegian Mother, Father and Child Cohort Study and included 705 ADHD cases, 397 ASD cases and 1034 controls. Cases were identified through linkage with the Norwegian Patient Registry. Maternal concentrations of 11 metals/elements were measured in blood at week 17 of gestation; cadmium; cesium; cobalt; copper; lead; magnesium; manganese; selenium; zinc; total arsenic; and total mercury. Multivariable adjusted logistic regression models were used to examine associations between quartile levels of individual metals/elements and outcomes. We also investigated non-linear associations using restricted cubic spline models. The joint effects of the metal/element mixture on ASD and ADHD diagnoses were estimated using a quantile-based g-computation approach. ResultsFor ASD, we identified positive associations (increased risks) in the second quartile of arsenic [OR = 1.77 (CI: 1.26, 2.49)] and the fourth quartiles of cadmium and manganese [OR = 1.57 (CI: 1.07 2.31); OR = 1.84 (CI: 1.30, 2.59)], respectively. In addition, there were negative associations between cesium, copper, mercury, and zinc and ASD. For ADHD, we found increased risk in the fourth quartiles of cadmium and magnesium [OR = 1.59 (CI: 1.15, 2.18); [OR = 1.42 (CI: 1.06, 1.91)]. There were also some negative associations, among others with mercury. In addition, we identified non-linear associations between ASD and arsenic, mercury, magnesium, and lead, and between ADHD and arsenic, copper, manganese, and mercury. There were no significant findings in the mixture approach analyses. ConclusionResults from the present study show several associations between levels of metals and elements during gestation and ASD and ADHD in children. The most notable ones involved arsenic, cadmium, copper, mercury, manganese, magnesium, and lead. Our results suggest that even population levels of these compounds may have negative impacts on neurodevelopment. As we observed mainly similarities among the metals’ and elements’ impact on ASD and ADHD, it could be that the two disorders share some neurochemical and neurodevelopmental pathways. The results warrant further investigation and replication, as well as studies of combined effects of metals/elements and mechanistic underpinnings.
Highlights
Attention-deficit/hyperactivity disorder (ADHD) and autism spec trum disorder (ASD) are neurodevelopmental disorders that interfere with learning and normal functioning during childhood and adolescence (Antshel et al, 2016; Kern et al, 2015)
Potential adjustment variables were selected a priori based on existing literature using a directed acyclic graph (DAG) approach (Greenland et al, 1999). We considered these as interdependent vari ables relevant for the current analysis: child sex, birth weight, birth year, and small for gestational age (SGA), maternal age at delivery, education, parity, pre-pregnancy body mass index (BMI, kg/m2), self-reported smoking and alcohol intake during pregnancy, as well as food frequency questionnaire (FFQ)-based estimates of seafood intake (g/day), and dietary iodine intake
We identified a non-linear (U-shaped) associa tion with prenatal lead exposure and autism spectrum disorder (ASD), while there were no such findings for attention-deficit/hyperactivity disorder (ADHD) diagnosis in children
Summary
Attention-deficit/hyperactivity disorder (ADHD) and autism spec trum disorder (ASD) are neurodevelopmental disorders that interfere with learning and normal functioning during childhood and adolescence (Antshel et al, 2016; Kern et al, 2015). Prenatal exposure to toxic metals or variations in maternal levels of essential elements during pregnancy may be a risk factor for neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in offspring. Objectives: We investigated whether maternal levels of toxic metals and essential elements measured in midpregnancy, individually and as mixtures, were associated with childhood diagnosis of ADHD or ASD. Maternal concentrations of 11 metals/elements were measured in blood at week 17 of gestation; cadmium; cesium; cobalt; copper; lead; magnesium; manganese; selenium; zinc; total arsenic; and total mercury. We identified non-linear associations between ASD and arsenic, mercury, magnesium, and lead, and between ADHD and arsenic, copper, manganese, and mercury. Conclusion: Results from the present study show several associations between levels of metals and elements during gestation and ASD and ADHD in children. The results warrant further investigation and replication, as well as studies of com bined effects of metals/elements and mechanistic underpinnings
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