Lithium naturally occurring in drinking water appeared to be a potential environmental risk factor for autism spectrum disorder (ASD), according to a population-based, case-control study from Denmark.
After adjustment for demographics, neighborhood socioeconomic factors, and ambient air pollutants, maternal prenatal exposure based on the estimated lithium level in the local drinking water was associated with a 23% increase in the odds for ASD in offspring (adjusted odds ratio [aOR] 1.23, 95% CI 1.17-1.29) for each interquartile range (IQR) increase.
Lithium exposures in the second and third quartiles -- ranging from groundwater concentrations 7.4 to 16.8 μg/L -- were associated with 24% to 26% higher odds for ASD diagnosis, Beate Ritz, MD, PhD, of the University of California Los Angeles, and colleagues reported in .
The highest quartile, exposed to lithium levels over 16.8 μg/L, had 46% higher odds of ASD in offspring (aOR 1.46, 95% CI 1.35-1.59) compared with the lowest quartile, exposed to less than 7.4 μg/L.
"It was definitely stronger and more of a consistent pattern than I may have guessed," Ritz told regarding the research team's findings.
Ritz said that if there are more studies that confirm similar findings, it will be important to inform individuals who have water from high-lithium systems or sources.
"It's really all about pregnancy because that is the really vulnerable period, and the first year of life," she said. "But what I'm a little worried about myself is general neurodevelopment and not just autism.... We want to give kids the best chance they have for brain development."
At the same time, it's important to note that "we haven't found the cause" when it comes to ASD, Ritz cautioned, and it remains rare.
The study included 8,842 children born from 2000 through 2013 who were diagnosed with ASD along with 43,864 control participants matched by birth-year and sex from the Danish Medical Birth Registry.
Researchers also geocoded all maternal residential addresses recorded in the Danish Civil Registration System during the interval of 9 months before until 9 months after a pregnancy. Groundwater is the main source of drinking water in Denmark, and it undergoes limited treatment, without chlorination.
In terms of generalizability, lithium concentrations in Danish drinking water (range 0.6-30.7 μg/L) were reasonably similar to what's been reported in U.S. drinking water, noted David Bellinger, PhD, MSc, of Boston Children's Hospital and Harvard Medical School, writing in an accompanying the study.
Levels are likely to increase due to mining to produce lithium-ion batteries for the growing number of electric vehicles, he wrote. "Eventually, these batteries will enter the waste stream, threatening additional contamination of water supplies."
Bellinger added that the "implications of the findings of this study for public health policy are complex," in part because such lithium levels in water "have also been linked to health benefits, specifically reductions in rates of hospitalization for psychiatric disorders and suicide."
"If all these of associations are valid," Bellinger wrote, "the wisdom of Solomon will be required to develop guidelines for lithium in drinking water that are maximally protective of the entire population."
Additional findings of the study included that analyses by ASD subtypes showed similar associations for autistic disorder cases (aOR 1.24, 95% CI 1.15-1.34, per IQR increase of estimated maternal exposure to lithium levels; and aOR 1.49, 95% CI 1.32-1.68, comparing the highest vs lowest quartile of lithium levels).
As for Asperger syndrome cases, the associations seemed to be driven predominantly by the highest exposure quartile, researchers added.
Researchers noted several limitations of their study, including lack of information on dietary and lifestyle factors, including drinking water habits. Among other potential limitations were that the study did not include data on maternal use of lithium medication, and that it may not be generalizable to other populations exposed to higher lithium concentrations.
Disclosures
Ritz reported grants from the National Institute of Environmental Health Sciences for research on autism in Denmark during the conduct of the study, and is a consultant for plaintiffs in a lawsuit concerning autism and lead, arsenic, and mercury in food. A co-author reported grants from the Novo Nordisk Foundation during the conduct of the study as well as grants from the National Institute of Environmental Health Sciences outside the submitted work.
Primary Source
JAMA Pediatrics
Liew Z, et al "Association between estimated geocoded residential maternal exposure to lithium in drinking water and risk for autism spectrum disorder in offspring in Denmark" JAMA Pediatr 2023; DOI: 10.1001/jamapediatrics.2023.0346.
Secondary Source
JAMA Pediatrics
Bellinger DC "Lithium in drinking water -- a novel environmental risk factor for autism spectrum disorder?" JAMA Pediatr 2023; DOI: 10.1001/jamapediatrics.2023.0330.