Exposure to heavy metals in utero and autism spectrum disorder at age 3

Abstract

Background: Autism spectrum disorder is a prevalent and heterogeneous neurodevelopmental disorder. Risk is attributed to genetic and prenatal environmental factors, though the environmental agents are incompletely characterized.Methods: In the Early Autism Risk Longitudinal Investigation (EARLI), an enriched-risk pregnancy cohort, maternal urinary metals concentrations at two time points during pregnancy were measured using inductively coupled plasma mass spectrometry. At age three, clinicians assessed autism spectrum disorder with DSM-5 criteria. Using multivariable logistic regression, we tested each metal for association with autism spectrum disorder status, adjusting for gestational age, child sex, and maternal education.Results: In this enriched-risk study sample (n=167), 18.6% of children were diagnosed with autism spectrum disorder, 31.1% were non-neurotypical, and 50.9% were males. Mothers averaged 34 years old and 57.5% had greater than high school education. Median urinary metals concentrations were 0.04 ppb antimony, 6.8 ppb arsenic, 1.8 ppb barium, 0.12 ppb cadmium, 3.9 ppb cesium, 0.66 ppb cobalt, 8.5 ppb copper, 0.26 ppb lead, 0.26 ppb manganese, 0.22 ppb mercury, 51.8 ppb molybdenum, 3.5 ppb nickel, 39 ppb selenium, 0.14 ppb thallium, 0.37 ppb tin, and 245 ppb zinc. In early pregnancy, an interquartile range increase in barium concentration was associated with 2.33 (1.13, 4.82) higher odds of autism spectrum disorder, an interquartile range increase of cesium with 2.65 (1.37,5.13) higher odds, and an interquartile range increase in zinc with 2.11 (1.21, 3.69) higher odds. Having cadmium concentration over the level of detection was associated with 2.78 (1.02, 7.59) higher odds of autism spectrum disorder. Longitudinal analyses and mixtures analyses will be presented.Conclusion: Exposure in utero to elevated metals levels (barium, cesium, cadmium, zinc), as measured via maternal urine, was associated with increased odds of developing autism spectrum disorder. Prenatal timing of exposure and longitudinal clinical evaluations are critical.