Prenatal, Early-Life Toxin, Nutrient Exposure Tied to Autism

Megan Brooks

June 02, 2017

Differences in the uptake of multiple toxic and essential elements during the second and third trimesters and early postnatal periods have been linked to an increased risk of developing autism spectrum disorders (ASDs), according to new research.

The analysis of baby teeth from twins discordant for autism showed that for siblings who developed ASD, uptake of the neurotoxin lead was higher and uptake of the essential nutrients manganese and zinc was lower.

"This study identifies environmental factors [for ASD] that are potentially modifiable," lead investigator Manish Arora, PhD, vice chair and associate professor, Department of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai in New York City, told Medscape Medical News.

"The fact that we found differences in metal uptake between twins, even identical twins, is important because it shows that the underlying causes of autism have a significant environmental component in addition to genetic risk factors," Dr Arora added.

The study was published online June 1 in Nature Communications.

Environmental Hit Occurs in the Womb

The researchers used validated tooth-matrix biomarkers to estimate prenatal and postnatal exposure to essential elements and toxic elements in 32 monozygotic and dizygotic twin pairs. They found "significant divergences" in metal uptake between persons with ASD and their control siblings during discrete developmental periods.

In persons with ASD, higher lead levels were observed during the prenatal period and first 5 months postnatally.

Levels of the essential elements zinc and manganese were also diminished in ASD patients. Zinc levels were lower in patients with ASD during the third trimester, and manganese levels were consistently lower in ASD patients both prenatally and postnatally. This deficiency was highest at age 4 months.

An "important finding is that the environmental 'hit' happens prenatally, prior to the onset of any symptoms," said Dr Arora.

"Very interestingly, the levels of manganese and lead in early life also predicted the severity of autism many years later," coinvestigator Abraham Reichenberg, PhD, professor of psychiatry and environmental medicine and public health at the Icahn School of Medicine, told Medscape Medical News.

"Our study suggests that metal toxicant uptake and essential element deficiency during specific developmental windows increases ASD risk and severity, supporting the hypothesis of systemic elemental dysregulation in ASD," the authors write.

They note that signs of ASD first manifest 6 to 12 months after birth, suggesting a narrow window for environmental factors to contribute to ASD risk. "Our results support this hypothesis, as the timing of divergence between ASD cases and their co-twins in lead, zinc and manganese was evident prenatally and in the early postnatal period," they note.

"These differences at specific developmental periods in early life for a range of toxic and essential elements suggest that there are multiple mechanisms leading to dysregulation, and endorse the higher vulnerability of the mid- to late-fetal period to the pathophysiological mechanisms underlying ASD," they add.

Important Work Ahead

It will be important to replicate the findings through additional studies in larger samples and "identify the pathways that are involved in the elemental dysregulation that is observed, which may eventually lead to interventions," said Dr Arora.

"It's important to remember," added Dr Reichenberg, "that there is a long way to go before the results of this study can be useful to families and individual patients. More research is needed so that we can understand how the interplay between nutrients, environmental toxins, and genes leads to the development of autism."

In particular, studies are needed to determine whether the discrepancies in the amount of certain metals and nutrients are due to differences in how much a fetus or child is exposed to them or occur because of a genetic difference in how a child takes in, processes, and breaks down these metals and nutrients.

The Seaver Center for Autism Research and Treatment at Mount Sinai is actively recruiting twins or siblings, both with and without ASD, for this study. More information if available by emailing the center at theseavercenter@mssm.edu.

The study was funded by the Beatrice and Samuel A. Seaver Foundation, the National Institute of Environmental Health Sciences, the Swedish Research Council, the European Union, and several Swedish foundations. The authors have disclosed no relevant financial relationships.

Nat Comm. Published online June 1, 2017. Full text

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