Background: Juvenile idiopathic arthritis (JIA) results from a complex interplay of genetic and environmental factors. Past efforts to identify JIA's environmental risk factors have been restricted due to limited high-quality data and small sample sizes, mirroring the rarity of the disease. In 2019, a Swedish prospective birth cohort study of 15 740 children (JIA cases n=41) showed that consuming fish ≥1/week during pregnancy and the first year of life was associated with up to a five-fold increased risk of JIA, compared to fish consumption <1/week. The increased risk was primarily attributed to elevated exposure to heavy metals [1]. Objectives: We aimed to investigate the association between maternal fish consumption and dietary mercury exposure during pregnancy and risk of JIA in a large population-based prospective cohort. Methods: We utilized the Norwegian Mother, Father, and Child Cohort Study (MoBa), which recruited pregnant women in 1999-2008. JIA cases were defined as having at least two ICD-10 codes (≥2 M08, ≥2 M09, or 1 M08 and 1 M09) via linkage to the Norwegian Patient Registry. Maternal fish consumption was assessed by a validated semi-quantitative food frequency questionnaire (FFQ) covering the first half of pregnancy [2]. High fish consumption was defined as exceeding the 90th percentile (P90): 252 g/week for lean and semi-oily fish, 157.5 g/week for oily fish, and 427 g/week for total fish intake. These were compared to low consumption (≤P90). We also examined associations with fish consumption across quintiles, using the first quintile as a reference. Mercury exposure from diet, validated in previous studies [3], was estimated from the FFQ. High mercury intake (>20 µg/week) was categorized as >P90, using the low intake group (≤P90) as reference. We used multivariable logistic regression analysis to explore the association between fish and mercury intake in pregnancy and JIA in offspring. Associations are reported as odds ratios adjusted for maternal factors: age, education, pre-pregnancy BMI, parity, daily caloric intake, inflammatory rheumatic disorders, as well as parental smoking in pregnancy. Results: Our analytical sample involved 73 819 mother-child pairs with 218 cases of JIA in the children. The pregnant women had a mean age of 30.3 years, a pre-pregnancy BMI of 24.1 kg/m2 and 25% had completed > four years of higher education. Among the mothers, 46% were primiparous and 2.9% had an inflammatory rheumatic disease. The median total fish intake was 218 g/week. We found a positive association between JIA and high consumption (>P90) of lean and semi-oily fish (adjusted odds ratio [aOR] 1.53, 95% CI 1.04-2.24), vs. low consumption (≤P90). No clear associations were observed between JIA and high consumption of oily (aOR 0.93, 95% CI 0.58-1.48) and total fish (aOR 1.1, 95% CI 0.71-1.71) vs. low. No associations were identified across quintiles of fish consumption with JIA risk. Notably, no association was found between JIA and high mercury intake (aOR 0.94, 95% CI 0.59-1.50) vs. low. Conclusion: We found an increased odds of JIA when the maternal intake exceeded 252g of lean or semi-oily fish per week compared with low intake. The magnitude of our effect estimates was substantially smaller than the Swedish study (1). We found no association between total fish consumption or estimated dietary mercury exposure and JIA. Further investigation is needed to clarify the role of heavy metals and other dietary contaminants in JIA etiology. REFERENCES: [1] Kindgren E, et al. Heavy metals in fish and its association with autoimmunity in the development of juvenile idiopathic arthritis: a prospective birth cohort study. Pediatr Rheumatol Online J. 2019;17(1):33. [2] Brantsaeter AL, et al. Validity of a new food frequency questionnaire for pregnant women in the Norwegian Mother and Child Cohort Study (MoBa). Matern Child Nutr. 2008;4(1):28-43. [3] Vejrup K, et al. Prenatal mercury exposure, maternal seafood consumption and associations with child language at five years. Environ Int. 2018;110:71-9. Acknowledgements: NIL. Disclosure of Interests: None declared.
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