Higher lithium levels in drinking water were associated with an increased odds of Wolff-Parkinson-White (WPW) syndrome diagnosis among children, according to new research. 

The findings in California, published in the Journal of Clinical Investigation, were comparable to those in a New York cohort. Combined, the studies included over 4 million children. Lithium, a metal found in the earth’s crust, can reach the water supply through natural cause, as well as human activities such as improper disposal of batteries and industrial discharge. 

“These data suggest that the development of these accessory pathways, responsible for clinically relevant arrhythmias and, at times, risks for sudden death, may have an identifiable and modifiable cause,” said Gregory Marcus, MD, MAS, study investigator and endowed professor in atrial fibrillation research at the University of California, San Francisco. “We therefore hope this might open up future research into the prevention of these accessory pathways from occurring in the first place.”

Atrioventricular accessory pathways have been understood for more than a century and treated for decades, yet little is known about why they occur, Marcus said. 

For the California study, Marcus and his team conducted a county-level ecological comparison of lithium levels in drinking water. 

They wanted to understand whether in utero exposure to lithium from environmental sources is associated with the prevalence of accessory pathways. Furthermore, they noted that the WPW pattern on an ECG represents the “most dangerous and clinically obvious manifestation of an accessory pathway.” 

The Lithium Link

The study included 2,329,090 patients (mean age, 8.2 ± 5.9 years; 47.8% female). Of these patients, 686 (0.03%) were diagnosed with WPW. 

Results showed that children in areas where lithium levels were at or above the 75th percentile, or 32.6 parts per billion, had a more than 70% greater odds of WPW (odds ratio [OR], 1.71; 95% CI, 1.44-2.03). The association remained following adjustment for sex, race, ethnicity, income, and insurance type (adjusted OR, 1.60; 95% CI, 1.34-1.90; P < .001 for both).

For areas above the lithium health-based screening limit, or greater than 10 parts per billion, the odds of WPW were 29% higher (OR, 1.29; 95% CI, 1.05-1.58; P = .015) or 33% higher after adjustment (adjusted OR, 1.33; 95% CI, 1.08-1.64; P = .0070).

A separate analysis of nearly 2 million children in New York demonstrated comparable findings, although the association was not significant at the higher lithium threshold. 

In a validation analysis, researchers observed that lithium levels in the 75th percentile or higher yielded a greater prevalence of supraventricular tachycardia, syncope, palpitations, and catheter ablation procedures.

“These data may point to variable amounts of lithium in drinking water as being relevant more broadly to public health,” Marcus said, “perhaps mostly to developing embryos in utero, suggesting future research to validate these findings and considering methods to mitigate this exposure might be worthwhile.”

Correlation, Not Causation

The researchers did not directly measure lithium exposure during pregnancy and therefore could not demonstrate cause of accessory pathways, said Raffaele Marfella, MD, PhD, who was not involved in the study.

“They estimated exposure using county-level water measurements linked to children’s subsequent residence, without knowing individual maternal intake or confirming residence throughout pregnancy,” said Marfella, professor of internal medicine and director of the department of advanced medical and surgical sciences at the University of Campania Luigi Vanvitelli in Naples, Italy. 

“Therefore, this is evidence supporting a hypothesis about prenatal environmental exposure,” he said. “Other water constituents, geographic differences, and variation in diagnostic ascertainment could still contribute to the association.”

As a result, Marfella said he would regard these findings as more relevant to research priorities than changing routine clinical practice. 

“The study does not establish an individual exposure threshold that causes harm, demonstrate that reducing exposure prevents WPW, or provide a sufficient basis for population-wide cardiac screening,” he said. “These findings alone would not justify advising pregnant women to avoid tap water or recommending routine testing for environmental lithium exposure.” 

Marfella also cautioned against changes to prescribed lithium treatment. “Patients should not stop or change prescribed lithium because of this study; treatment decisions during pregnancy require an individualized assessment with the relevant specialists, balancing maternal health and fetal risks.

“If future studies confirm the association, using directly measured prenatal exposure and demonstrate a causal relationship,” he continued, “the implications could extend to water-quality assessment and targeted prevention. For now, the appropriate response is careful follow-up research and proportionate communication of uncertainty.”

Marcus and Marfella reported no relevant financial relationships.

Brian Ellis is a freelance writer and editor who lives in Southwest Virginia.