Letter to the editor regarding Hall et al. (2023): Fluoride exposure and hypothyroidism in a Canadian pregnancy cohort

Letter to the Editor

Dear Editor,

In our recently published study evaluating the potential thyroid-disrupting effects of fluoride exposure in pregnancy (Hall et al., 2023)¹, we found that pregnant women exposed to higher concentrations of fluoride in drinking water were at an increased risk of hypothyroidism. Specifically, a 0.5 mg/L increase in water fluoride concentration – roughly the difference between a fluoridated and non-fluoridated community – was associated with a 65% greater odds of having a diagnosis or meeting criteria for primary hypothyroidism (Table 1). In contrast, maternal urinary fluoride concentration was not significantly associated with primary hypothyroidism, perhaps because urinary fluoride is not a stable and chronic measure of exposure as are fluoride levels in municipal water.¹

Table 1.

Association between water fluoride concentration, and subclinical and primary hypothyroidism in pregnant women participating in the MIREC study, with consideration for duration at current residence.

	Model 1a: unadjusted				Model 2b: covariate adjusted				Model 2 + Normal TPOAbc				Model 2 + High TPOAbd
	n	OR	95% CI	p	n	aOR	95% CI	p	n	aOR	95% CI	p	n	aOR	95% CI	p
Primary hypothyroidism
Original samplee	1185	1.71	1.10,2.67	0.02	1105	1.65	1.04,2.60	0.03	1094	2.85	1.25,6.50	0.01	1094	0.88	0.45,1.72	0.71
Residence-restricted samplef	944	1.84	1.12,3.05	0.02	889	1.80	1.07,3.01	0.03	880	3.88	1.51,9.97	0.01	880	0.67	0.30,1.47	0.31
Subclinical hypothyroidism
Original samplee	1185	1.12	0.71,1.74	0.63	1105	1.15	0.73,1.82	0.54	1094	1.15	0.67,1.99	0.61	1094	1.13	0.48,2.70	0.78
Residence-restricted samplef	944	1.28	0.77,2.12	0.35	889	1.28	0.76,2.16	0.35	880	1.31	0.70,2.46	0.40	880	1.05	0.39,2.86	0.93

^aModel 1: multinomial logistic regression models of water fluoride concentration predicting risk of either primary or subclinical hypothyroidism, not adjusted for covariates.

^bModel 2: multinomial logistic regression models of water fluoride concentration predicting risk of either primary or subclinical hypothyroidism, adjusted for maternal age, pre-pregnancy BMI, race, and level of education.

^cModel 2 + normal TPOAb: multinomial logistic regression models of water fluoride concentration predicting risk of either primary or subclinical hypothyroidism for women with normal levels of TPOAb (i.e., < 5.61 IU/mL; n= 744 – 917).

^dModel 2 + high TPOAb: multinomial logistic regression models of water fluoride concentration predicting risk of either primary or subclinical hypothyroidism for women with elevated levels of TPOAb (i.e., ≥ 5.61 IU/mL; n= 136 – 177).

^eModels include all pregnant women with available water fluoride, hypothyroidism, and covariate data (i.e., original models presented in Hall et al., 2023).

^fModels restricted to include only pregnant women who reported living at their current residences for at least one year.

OR= Odds ratio, aOR= adjusted odds ratio; reported for every 0.5 mg/L or 0.5 mg/day increase in water fluoride concentration.

In February 2024, findings from Hall et al. (2023) were examined during the second phase of the federal trial between the Food and Water Watch et al. vs the United States Environmental Protection Agency.² During the trial, a question was raised about whether we had examined duration at residence in our models of drinking-water fluoride concentration with maternal hypothyroidism to verify whether water fluoride was an indicator of chronic exposure. Although we had not examined this question in our article, we have since conducted an analysis accounting for duration at current residence. To do this, we used multinomial logistic regression to estimate associations between water fluoride concentrations and the odds of primary (n= 65) or subclinical (n= 63) hypothyroidism (relative to euthyroidism), restricting the analysis to women who reported living at their current residences for at least one year.

We found that fluoride in drinking water was associated with greater odds of primary hypothyroidism among pregnant women who reported living at their current residences for one year or more. The adjusted odds ratio (aOR) per 0.5 mg/L rise in water fluoride concentration increased from 1.65 (95% CI: 1.04, 2.60) in the original sample of 1105 women to 1.80 (95% CI: 1.07, 3.01) in the residence-restricted sample of 889 women (Table 1). The association between water fluoride concentration and subclinical hypothyroidism remained non-significant (Table 1).

Consistent with our findings reported in Hall et al. (2023)¹, we observed a statistically significant interaction between water fluoride concentration and maternal thyroid peroxidase antibody (TPOAb) status in predicting risk of primary hypothyroidism (p interaction term= .01). In the original model, we found that women with normal TPOAb levels were 2.85 (95% CI = 1.25, 6.50) times more likely to have or meet criteria for primary hypothyroidism per 0.5 mg/L increase in water fluoride concentration. In the residence-restricted sample, we found that women with normal TPOAb levels who lived at the same residence for at least one year were 3.88 (aOR for 0.5 mg/L increase in water fluoride; 95% CI: 1.51, 9.97) times more likely to have or meet criteria for primary hypothyroidism (Table 1). In contrast, water fluoride concentration was not significantly associated with primary hypothyroidism among women with elevated TPOAb levels (aOR for 0.5 mg/L increase: 0.67; 95% CI: 0.30,1.47) (Table 1).

Accounting for duration at residence, in addition to excluding women who did not report drinking tap water in pregnancy, gave us more confidence that water fluoride was a valid measure of chronic fluoride exposure. We were able to infer with greater certainty that pregnant women living in fluoridated communities were consuming fluoridated water for an extended period, prior to and at the beginning of pregnancy. Taken together, these additional findings provide further evidence that fluoride in drinking water may contribute to the development of primary hypothyroidism in women, particularly among those who have normal TPOAb levels. These results – which indicate that water fluoridation is not associated with autoimmune hypothyroidism – are critical for improving our understanding of fluoride’s potential thyroid-disrupting effects.