Fluoride exposure and hypothyroidism in a Canadian pregnancy cohort

Background: While fluoride can have thyroid-disrupting effects, associations between low-level fluoride exposure and thyroid conditions remain unclear, especially during pregnancy when insufficient thyroid hormones can adversely im-pact offspring development.Objectives: We evaluated associations between fluoride exposure and hypothyroidism in a Canadian pregnancy cohort.Methods: We measured fluoride concentrations in drinking water and three dilution-corrected urine samples and esti-mated fluoride intake based on self-reported beverage consumption. We classified women enrolled in the Maternal -Infant Research on Environmental Chemicals Study as euthyroid (n = 1301), subclinical hypothyroid (n = 100) or primary hypothyroid (n = 107) based on their thyroid hormone levels in trimester one. We used multinomial logistic regression to estimate the association between fluoride exposure and classification of either subclinical or primary hy-pothyroidism and considered maternal thyroid peroxidase antibody (TPOAb) status, a marker of autoimmune hypo-thyroidism, as an effect modifier. In a subsample of 466 mother-child pairs, we used linear regression to explore the association between maternal hypothyroidism and child Full-Scale IQ (FSIQ) at ages 3-to-4 years and tested for effect modification by child sex.Results: A 0.5 mg/L increase in drinking water fluoride concentration was associated with a 1.65 (95 % confidence in-terval [CI]: 1.04, 2.60) increased odds of primary hypothyroidism. In contrast, we did not find a significant association between urinary fluoride (adjusted odds ratio [aOR]: 1.00; 95%CI: 0.73, 1.39) or fluoride intake (aOR: 1.25; 95%CI: 0.99, 1.57) and hypothyroidism. Among women with normal TPOAb levels, the risk of primary hypothyroidism increased with both increasing water fluoride and fluoride intake (aOR water fluoride concentration: 2.85; 95%CI:1.25, 6.50; aOR fluoride intake: 1.75; 95%CI: 1.27, 2.41). Children born to women with primary hypothyroidism had lower FSIQ scores compared to children of euthyroid women, especially among boys (B coefficient: -8.42; 95 % CI: -15.33, -1.50).Discussion: Fluoride in drinking water was associated with increased risk of hypothyroidism in pregnant women. Thy-roid disruption may contribute to developmental neurotoxicity of fluoride.