Prenatal exposure to perchlorate, thiocyanate, and nitrate: Associations with maternal thyroid function and child neurodevelopment in the MARBLES cohort

Perchlorate, thiocyanate, and nitrate are widespread environmental anions that inhibit iodide uptake via the sodium–iodide symporter (NIS), potentially disrupting maternal thyroid hormone production. Maternal thyroid dysfunction during pregnancy has been linked to child neurodevelopment, but the interrelationships among prenatal exposure to these NIS inhibitors, maternal thyroid function, and child neurodevelopment remain unclear. We analyzed 195 mother–child pairs from the MARBLES prospective pregnancy cohort, enriched for familial likelihood of autism. Prenatal urinary perchlorate, thiocyanate, and nitrate and maternal serum thyroid function tests (TFTs) were measured during pregnancy. Child neurodevelopmental outcomes were classified as autism ( n = 49), non-typically developing (non-TD, n = 24), or TD ( n = 122). Robust Poisson regression was used to estimate relative risks, and exploratory single-mediator analyses were conducted to evaluate potential indirect effects through maternal thyroid function. Primary analyses detected no statistically significant associations between prenatal NIS inhibitor exposures and child neurodevelopment. Higher nitrate and perchlorate-equivalent concentrations were associated with increased maternal total thyroxine levels after false discovery rate correction. Exploratory mediation analyses did not detect statistically significant indirect effects through maternal TFTs. However, these findings were inconclusive given the limited statistical power to detect small indirect effects. Overall, prenatal NIS inhibitor exposures were associated with selected maternal thyroid markers but not significantly associated with child neurodevelopment in the current analytical sample. Larger studies are needed to further evaluate the potential role of maternal thyroid function in these associations.