Elevated lithium levels in drinking water are associated with higher prevalence of Wolff-Parkinson-White diagnoses

BACKGROUND: Supraventricular tachycardia (SVT) and Wolff-Parkinson-White (WPW) are potentially highly symptomatic and, rarely, lethal arrhythmias associated with atrioventricular accessory pathways. While the etiology of accessory pathways remains largely unknown, they are frequently observed with Ebstein's Anomaly, a congenital heart disease associated with maternal medicinal lithium use. Therefore, we evaluated whether in utero exposure to lithium from environmental sources is associated with the prevalence of accessory pathways. METHODS: We conducted a county-level ecological comparison of lithium levels in drinking water versus prevalence of WPW diagnoses among patients < 18-years-old in California using multivariable logistic regression. Children were analyzed given their high likelihood to reside in the same county during fetal development. WPW cases were identified using diagnostic codes. Positive and negative controls, including falsification endpoints, were analyzed. RESULTS: Among 2,329,090 patients (mean age 8.2 ± 5.9 years, 47.8% female), 686 (0.03%) were diagnosed with WPW. Areas where lithium levels ≥ 75th percentile were associated with 71% greater odds of WPW (OR 1.71, 95% CI 1.44 to 2.03). Areas above the lithium health-based screening limit had 29% greater odds of WPW (OR 1.29, 95% CI 1.05 to 1.58). Similar results existed in a New York statewide cohort. In validation analyses, areas where lithium levels ≥ 75th percentile were associated with a higher prevalence of SVT, syncope, palpitations, and catheter ablation procedures. CONCLUSIONS: Higher lithium levels in drinking water were associated with a greater prevalence of childhood-diagnosed WPW, implicating a potentially modifiable risk factor for the development of accessory pathways.