Higher Lithium Levels in Drinking Water May Raise Autism Risk

Pregnant women whose household tap water had higher levels of lithium had a moderately higher risk of their offspring being diagnosed with autism spectrum disorder, according to a new study led by researchers at the Yale School of Public Health and UCLA Health.

The study, published April 3 in JAMA Pediatrics, is believed to be the first to identify naturally occurring lithium in drinking water as a possible environmental risk factor for autism. The researchers note that the exact cause of autism spectrum disorder remains unclear, and their findings only show a possible association between lithium exposure and autism diagnosis. The study did not conclude that lithium exposure in tap water is a direct cause of autism disorder.

The study results are based on an investigation of whole population medical registry data in Denmark with high completion and accuracy. The researchers said the findings still need to be replicated in other populations and areas of the world.

“This study is important because prior research has shown that ingestion of chronic and low-dose lithium from drinking can influence the occurrence of adult-onset neuropsychiatric disorders, but no studies have assessed whether lithium from drinking water consumed by pregnant women affects their child’s neurodevelopment,” said Zeyan Liew, PhD, MPH, assistant professor of epidemiology (environmental health) at the Yale School of Public Health and the study’s first author.

“Any drinking water contaminants that may affect fetal development require intense scrutiny,” Liew said. “Currently, lithium levels in drinking water are not routinely monitored.”

Some experimental research has indicated lithium, which is among several naturally occurring metals found in water, could affect an important molecular pathway involved in neurodevelopment and autism, said senior study author Dr. Beate Ritz, MD, professor of neurology in the David Geffen School of Medicine at UCLA and professor of epidemiology and environmental health at the UCLA Fielding School of Public Health. Because of lithium’s mood-stabilizing effects, some lithium compounds have been used as a treatment for depression and bipolar disorders. However, there is also increasing evidence associating lithium use in pregnancy with a higher risk of miscarriage and cardiac anomalies or defects in newborns leading to debate about the safety of lithium intake during pregnancy.

In conducting the study, Yale and UCLA researchers worked with colleagues in Denmark who analyzed lithium levels in 151 public waterworks in Denmark, representing the water supply for about half of the country’s population. To identify which waterworks supplied mothers’ homes at the time of their pregnancy, the researchers used address information from Denmark’s comprehensive civil registry system. Using a nationwide database of patients with psychiatric disorders, the researchers identified children who were born in 1997-2013, and compared 12,799 diagnosed with autism against 63,681 children who did not have an autism diagnosis. The researchers also controlled for maternal characteristics, some socioeconomic factors, and air pollution exposures, all of which have been linked to increased risk of autism in children.

As lithium levels increased, so did the risk of an autism diagnosis, the researchers reported. Compared to the lowest quartile of recorded lithium levels – in other words, those in the 25th percentile – lithium levels in the second and third quartiles were associated with a 24-26% higher risk of autism. In the highest quartile, the risk was 46% higher compared to the lowest quartile.

The researchers found a similar relationship between increased lithium levels and a higher risk of autism diagnosis when the data were broken down by subtypes of the disorder. They also found the association between lithium levels and autism risk was slightly stronger for those living in urban areas compared to smaller towns and rural areas. Overall, lithium levels in Denmark’s water, when compared to other countries, are likely in the low to moderate range, Ritz said.

In addition to Denmark’s comprehensive civil databases that have proven to be valuable resources for public health researchers, several other factors made Denmark ideal for this study. Denmark’s consumption of bottled water ranks among the lowest in Europe, meaning Danes largely rely on tap water. The country also has a robust system for measuring trace metals and other contaminants in its water supply.

Nicole Deziel, PhD, MPH, an associate professor of epidemiology (environmental health sciences) at YSPH and an expert in environmental contaminants, said the study has several important implications.

“There has been a substantial growth in the commercial use of lithium as a critical component of batteries for mobile electronic devices and electric vehicles,” said Deziel, who was not involved in the study. “Mismanagement of wastes from lithium extraction or improper disposal of lithium-containing products could increase contamination of drinking water supplies.”

There is no U.S. federal drinking water standard for lithium, Deziel said. “As we move away from fossil fuels to slow climate change, we must embrace new technologies responsibly, so we don’t create new environmental health hazards. Understanding the potential public health impacts of lithium is important for populations exposed now and to help inform a responsible energy transition,” she said.

Other study authors include Qi Meng and Qi Yan, both of UCLA, and Danish researchers Jörg Schullehner, Birgitte Hansen, Søren Munch Kristiansen, Denitza D. Voutchkova, Jørn Olsen, Annette Kjær Ersbøll, Matthias Ketzel, and Ole Raaschou-Nielsen.

The study was supported by the National Institute of Environmental Health Sciences (NIEHS; R21ES024269). Schullehner was supported by the Danish Big Data Centre for Environment and Health, which was funded by the Novo Nordisk Foundation Challenge Programme (grant NNF17OC0027864). The authors declared no competing interests.

Content from a UCLA Health press release was used in this article.