Maternal Exposure to Lithium in Drinking Water May Up Autism Risk in Offspring

Maternal exposure to lithium in drinking water was associated with a higher risk for autism in offspring.

Children of women whose drinking water contains lithium are at an elevated risk of developing autism spectrum disorder (ASD), according to the findings of a retrospective study published in JAMA Pediatrics.

In previous studies, incident miscarriage and heart malformation in children were more common after maternal lithium therapy for bipolar disorder. Further concern has been raised about the potential effect of maternal lithium exposure on childrens’ neural development, as lithium crosses both the placenta and the fetus’s blood-brain barrier. Furthermore, lithium alters Wnt/β-catenin signaling; this pathway is crucial in neurologic development and its alteration has been implicated in ASD.

Low levels of lithium occur naturally in groundwater, which is Denmark’s exclusive source of drinking water. This prompted the question whether neurodevelopmental disorders such as ASD are more common in areas with higher groundwater lithium levels.

Researchers conducted a case-control study of Denmark’s birth registry in 8,842 children with ASD, born between 2000 and 2013, and diagnosed with ASD between those dates and 2016. The children were matched with children without an ASD diagnosis, in a 1:5 ratio, by age and birth year.

[N]aturally occurring lithium in drinking water may be a novel environmental risk factor for ASD development that requires further scrutiny.

The researchers linked the mothers’ residential addresses with model estimates of local groundwater lithium concentration. This allowed them to examine risk for an ASD diagnosis, in logistic regression models, with respect to local lithium exposure, adjusted for maternal age, maternal smoking, urban vs rural residence, ambient air pollution, and socioeconomic status. The researchers also conducted analyses stratified by ASD subtype, child sex, and birth year.

The research team found that groundwater lithium exposure was associated, in a dose-dependent manner, with higher odds of ASD developing in offspring. Measured as a continuous variable, each increase in lithium concentration interquartile range (IQR) increased the odds of an ASD diagnosis by 23% (adjusted odds ratio (aOR), 1.23; 95% CI, 1.17-1.29), in the fully adjusted regression model.

When exposures were categorized by quartile, this dose-dependent increase in diagnosis was largest in the highest quartile (lithium concentrations higher than 16.8 μg/L); these most-exposed children had 46% higher odds compared to the lowest quartile of exposure (aOR, 1.46; 95% CI, 1.35-1.59). Children in the second and third quartiles were between 24% and 26% more likely to receive an ASD diagnosis than those in the lowest exposure quartile. These associations remained present among subtypes of ASD, including autism, Asperger syndrome, and pervasive developmental disorder, and were slightly stronger for families living in urban areas than in smaller municipalities.

“[N]aturally occurring lithium in drinking water may be a novel environmental risk factor for ASD development that requires further scrutiny,” the researchers stated.
Specifically, they highlighted that environmental covariables, including exposure to iodine or other contaminants, and other maternal nutritional and lifestyle data should be studied. However, the researchers noted, “each of the potential confounding factors discussed are unlikely to be strongly enough associated with ASD and with lithium exposure such that this would nullify the observed associations.”

There are several study limitations that warrant mention, including a lack of information on dietary and lifestyle factors, such as habits of water consumption, not measuring the actual sources of water mothers consumed, and not considering childhood exposure.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References:

Liew Z, Meng Q, Yan Q, 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. Published online April 3, 2023. doi:10.1001/jamapediatrics.2023.0346