Exposure resulted from consumption of fish during pregnancy or early life
by Nancy Walsh, Senior Staff Writer, MedPage Today
July 09, 2019
Exposure to heavy metals through fish consumption in utero or during the first year of life was associated with a five-fold increased risk of subsequent development of juvenile idiopathic arthritis (JIA), Swedish researchers found.
The odds ratio for JIA among children whose mothers ate fish more than once a week during pregnancy was 4.5 (95% CI 1.95-10.4, P<0.001), according to Erik Kindgren, MD, and colleagues from Linköping University in Linköping.
And for children who themselves consumed fish more than once a week during the first year of life, the odds ratio was 5.1 (95% CI 2.1-12.4, P<0.001), they reported in Pediatric Rheumatology.
The cause of JIA is not known, but a common feature is the presence of antinuclear antibodies (ANA), which also are seen in other autoimmune diseases. Because treatments have thus far had suboptimal efficacy, prevention efforts have been the focus of increased attention, such as with early life nutrition. Kindgren’s group previously identified longer breastfeeding with a lower risk of JIA.
“Increased knowledge of the role of early nutrition and its association with autoimmunity is of crucial importance, as dietary recommendations may help to prevent these chronic diseases,” they wrote.
Therefore, they analyzed data from enrollees in the All Babies in Southeast Sweden project for the years 1997 to 1999 and the Swedish pediatric JIA registry, identifying 41 cases with completed questionnaires about diet, lifestyle, and environmental exposures. These were compared with almost 16,000 controls.
Biologic samples were obtained at birth and throughout childhood, and analyzed for factors such as ANA positivity. Prenatal heavy metal exposure was assessed in cord blood samples.
Almost half of the cases had the oligoarticular subtype of JIA.
A total of 87% of children with JIA had been exposed to fish through maternal consumption during pregnancy or during their first year of life compared with 56% of controls, for an adjusted odds ratio of 5.4 (95% CI 1.9-15.4, P=0.002).
Early fish exposure also was associated with an increased risk of ANA positivity (OR 2.2, 95% CI 1.4-3.6, P=0.002), and all children who were ANA positive had consumed fish more than once weekly during their first year.
Among children with JIA, mean cord blood concentrations of several heavy metals were significantly higher than among controls:
- Aluminum: 11.2 vs 6.1 µg/L (P<0.001)
- Cadmium: 0.19 vs 0.07 µg/L (P<0.001)
- Mercury: 0.33 vs 0.24 µg/L (P<0.001)
- Lithium: 2.79 vs 1.01 µg/L (P<0.001)
In addition, more than half of the JIA children had concentrations of these metals two standard deviations above the mean.
The frequency of maternal fish consumption during pregnancy correlated with concentrations of cadmium, lithium, and mercury. The frequency of maternal fish consumption from the Baltic Sea correlated with concentrations of cadmium, and the consumption of fish from other oceans correlated with concentrations of cadmium, lithium, and mercury.
In discussing their findings, the authors noted that fish consumption could help reduce the likelihood of inflammatory and autoimmune diseases because of the presence of long-chain polyunsaturated fatty acids and other micronutrients. However, contamination of fish with polychlorinated compounds, dioxin, and heavy metals could outweigh the benefits.
For the specific contaminants, they noted that cadmium has been implicated as a potential trigger for rheumatoid arthritis, particularly with inhalation during smoking. Dietary exposure also has been observed, and has been linked with a proinflammatory state and cytokine release in animals.
Furthermore, “humans do not have an effective elimination pathway for cadmium, and as a consequence the half-life of cadmium in the body is estimated to be 15-20 years,” the researchers explained.
Aluminum is a well recognized immune system stimulant, which is why it is used as a vaccine adjuvant, and induces various proinflammatory cytokines such as interleukins 1 and 6.
Mercury too can induce autoimmunity in murine models, and in humans, occupational mercury exposure has been associated with high levels of ANA. Lithium also has been implicated in elevations of ANA among patients with affective disorders being treated with this agent.
“Thus, it is reasonable to believe that the increased concentrations of cadmium, aluminum, mercury, and lithium may play a role in changes in the immune balance, which could contribute to the development of autoimmune rheumatic diseases,” Kindgren and colleagues concluded.
Consideration should be given to including cautions in future nutrition guidelines against heavy metal exposure during pregnancy and early life, they suggested.
A study limitation was the small sample of JIA patients.
The study was supported by the Swedish Child Diabetes Foundation, the Juvenile Diabetes Research Foundation, and the Medical Research Council of Southeast Sweden.
The authors disclosed support from the Research Unit of Kalmar County Council, the Research Fund at Skaraborg Hospital, Skaraborg Research and Development Council, the Swedish Rheumatism Association, and the Jerring Foundation.
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Pediatric Rheumatology