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NIH: Possible link between exposure to metals, risk for autism

When using novel biomarkers of early life exposure, researchers found differences in uptake of multiple toxic and essential elements over the second and third trimesters and early postnatal periods in monozygotic and dizygotic twins discordant for autism spectrum disorder, according to findings recently published in Nature Communications.

Researchers also noted that the critical development window was different for each element, suggesting that systemic elemental dysregulation may serve an important role in autism spectrum disorder (ASD) etiology.

“While substantial progress has been made in identifying genetic determinants of autism risk environmental factors, especially modifiable environmental exposures, remain understudied,” Manish Arora, PhD, MPH, BDS, department of environmental medicine and public health, Icahn School of Medicine at Mount Sinai, New York City, and colleagues wrote.

Researchers mapped the growth rings in baby teeth with lasers and looked at patterns of metal uptake from 32 pairs of twins and 12 individual twins. These patterns were then compared in twins where only one of the children had autism, as well as in twins where both or neither had autism.

They found that lead levels were higher among twins with ASD, at different times pre- and postnatally. Tin levels and strontium levels were also higher in the twins with ASD. Levels of manganese, zinc and chromium were lower in twins with ASD, at different time prenatally and postnatally. They also found:

•lead levels were consistently higher in ASD cases than their non-ASD co-twins from 20 weeks before birth to 30 weeks after birth; however, after adjusting for intratwin correlations, this association was only evident between weeks 10 to 20 postnatally;

•lead levels in ASD cases were at their greatest levels — 1.5 times higher than in their co-twins — at 15 weeks postnatally after considering the average difference in co-twins;

•manganese levels were consistently lower and statistically significant in ASD cases between 10 weeks prenatally to birth and subsequently postnatal from weeks 5 to 20; the greatest difference was observed at postnatal week 15 when cases had 2.5 times lower manganese than their co-twins;

•zinc was deficient in ASD cases from 10 weeks prenatally to approximately 5 weeks postnatally, with the ASD cases showing 1.28 times lower levels than their co-twins 8 weeks prenatally;

•strontium was higher in ASD cases throughout the study, a difference that was most pronounced during weeks 22 to 30 afterbirth;

•chromium was lower in cases than their control twins, with most pronounced differences detected from 20 to 15 weeks prenatally; and

•tin levels were higher in ASD cases, a difference that was statistically significant between 20 and 16 weeks before birth.

Researchers also correlated the tooth-matrix biomarkers with the severity of ASD approximately 10 years later as determined by the second editions of the Autism Diagnostic Observation Schedule and Social Responsiveness Scale. They found:

•manganese was inversely associated with autistic traits defined in the Social Responsibility Scale, with the strongest association at 15 weeks;

•manganese had the strongest association with ASD severity based on the Autism Diagnostic Observation Schedule at 12 weeks; and

•lead was statistically and significantly associated with Autism Diagnostic Observation Schedule from 10 weeks before birth to 30 weeks after birth, with strongest association 5 weeks prenatally.

“Early 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,” Arora and colleagues wrote. “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.”

Researchers also noted that their findings support the joint interaction of environmental exposures with genetic variations in the etiology of ASD observed in other recent studies. They also suggested that larger studies be conducted to confirm their findings. – by Janel Miller

Disclosure: The researchers report no relevant financial disclosures.