Association of maternal fluoride exposure during pregnancy with increased size at birth and the potential mediation effect by maternal thyroid hormones: the Swedish NICE birth cohort

BACKGROUND AND AIM: Observational studies have indicated that maternal fluoride exposure during gestation may impair child neurodevelopment but a potential impact on birth outcomes is understudied. The aim of the study is to evaluate the impact of gestational fluoride exposure on birth outcomes and assess the potential mediating role of maternal thyroid hormones. METHODS: We studied 583 mother-child pairs in the NICE cohort in northern Sweden, where drinking water fluoride varies considerably. Fluoride concentration was measured in urine at gestational week 29 using an ion selective electrode. Plasma levels of free and total thyroxine and triiodothyronine, and thyroid stimulating hormone at gestational week 29 were measured with electrochemiluminescence immunoassays. The infant’s length, head circumference, weight, and gestational age at birth were extracted from hospital records. RESULTS: Median maternal urinary fluoride concentration was 0.7 mg/L (5th-95th percentile 0.3-1.9 mg/L; specific gravity adjusted). In multivariable-adjusted regression models, every doubling of maternal urinary fluoride was associated with a mean increase in birth length by 0.4 cm (95%CI: 0.2, 0.6), head circumference by 0.18 cm (95%CI: 0.04, 0.31), and weight by 67 g (95%CI: 22, 112), as well as an increased odds of being born large for gestational age (OR=1.49, 95%CI: 1.11, 2.02). Every doubling of maternal urinary fluoride was also associated with a mean increase in the plasma tT3 level by 0.04 µmol/L (95%CI: 0.00, 0.09) but with no other marker of thyroid functioning. In mediation analysis, maternal tT3 levels explained only about 10% of the urinary fluoride-birth length/weight associations. CONCLUSIONS: Gestational fluoride exposure was associated with increased size at birth and even increased odds of being born large for gestational age. The observed associations were not explained by maternal thyroid hormone levels. KEYWORDS: urinary fluoride, pregnancy, birth length, head circumference at birth, birth weight, large for gestational age, thyroid hormones