Association Between Maternal Fluoride Exposure During Pregnancy and IQ Scores in Offspring in Canada
Authors: Pierre Ayotte
Rivka Green
Richard Hornung
Bruce Lanphear
Raichel Neufeld
E Angeles Martinez-Mier
Gina Muckle
David Flora
Christine Till
Journal: JAMA Pediatrics (2019)
Discipline: CLINICAL MEDICINE
Keywords: fluoride exposure; pregnancy; IQ scores; neurotoxicity; community water fluoridation
Affiliations: Faculty of Health, York University, Toronto, Ontario, Canada, Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada, Child and Family Research Institute, British Columbia Children’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada, Pediatrics and Environmental Health, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, School of Dentistry, Indiana University, Indianapolis, Department of Social and Preventive Medicine, Laval University, Québec City, Québec, Canada, Centre de Recherche du CHU de Québec, Université Laval, Québec City, Québec, Canada, School of Psychology, Laval University, Québec City, Québec, Canada

Abstract:  Importance: The potential neurotoxicity associated with exposure to fluoride, which has generated controversy about community water fluoridation, remains unclear. Objective: To examine the association between fluoride exposure during pregnancy and IQ scores in a prospective birth cohort. Design, setting, and participants: This prospective, multicenter birth cohort study used information from the Maternal-Infant Research on Environmental Chemicals cohort. Children were born between 2008 and 2012; 41% lived in communities supplied with fluoridated municipal water. The study sample included 601 mother-child pairs recruited from 6 major cities in Canada; children were between ages 3 and 4 years at testing. Data were analyzed between March 2017 and January 2019. Exposures: Maternal urinary fluoride (MUFSG), adjusted for specific gravity and averaged across 3 trimesters available for 512 pregnant women, as well as self-reported maternal daily fluoride intake from water and beverage consumption available for 400 pregnant women. Main outcomes and measures: Children's IQ was assessed at ages 3 to 4 years using the Wechsler Primary and Preschool Scale of Intelligence-III. Multiple linear regression analyses were used to examine covariate-adjusted associations between each fluoride exposure measure and IQ score. Results: Of 512 mother-child pairs, the mean (SD) age for enrollment for mothers was 32.3 (5.1) years, 463 (90%) were white, and 264 children (52%) were female. Data on MUFSG concentrations, IQ scores, and complete covariates were available for 512 mother-child pairs; data on maternal fluoride intake and children's IQ were available for 400 of 601 mother-child pairs. Women living in areas with fluoridated tap water (n = 141) compared with nonfluoridated water (n = 228) had significantly higher mean (SD) MUFSG concentrations (0.69 [0.42] mg/L vs 0.40 [0.27] mg/L; P = .001; to convert to millimoles per liter, multiply by 0.05263) and fluoride intake levels (0.93 [0.43] vs 0.30 [0.26] mg of fluoride per day; P = .001). Children had mean (SD) Full Scale IQ scores of 107.16 (13.26), range 52-143, with girls showing significantly higher mean (SD) scores than boys: 109.56 (11.96) vs 104.61 (14.09); P = .001. There was a significant interaction (P = .02) between child sex and MUFSG (6.89; 95% CI, 0.96-12.82) indicating a differential association between boys and girls. A 1-mg/L increase in MUFSG was associated with a 4.49-point lower IQ score (95% CI, -8.38 to -0.60) in boys, but there was no statistically significant association with IQ scores in girls (B = 2.40; 95% CI, -2.53 to 7.33). A 1-mg higher daily intake of fluoride among pregnant women was associated with a 3.66 lower IQ score (95% CI, -7.16 to -0.14) in boys and girls. Conclusions and relevance: In this study, maternal exposure to higher levels of fluoride during pregnancy was associated with lower IQ scores in children aged 3 to 4 years. These findings indicate the possible need to reduce fluoride intake during pregnancy. 

Retracted: No

PubPeer comments:
 See https: www.skepticalraptor.com skepticalraptorblog.php fluoride-lowers-iq-vaccine-deniers-study-useless for extensive comments on this paper. See also https: jamanetwork.com journals jamapediatrics article-abstract 2748626 (an Editorial) and https: jamanetwork.com journals jamapediatrics article-abstract 2748628 (an Editor s Note). Both refer to this article. , 
 1: As this study seeks to draw conclusions about the cognitive effects of community water fluoridation it is surprising that it does not discuss, or even cite, the only other study comparing IQ values from fluoridated and unfluoridated areas u2013 Broadbent et al (2015) . This is a serious omission, and it is surprising that it was not picked during the peer review of the paper. Taking the reported values for IQ in Table 1 of the paper the conclusion should be that fluoridation has no effect on IQ u2013 as was Broadbent et alu2019s conclusion. The IQ data for this paper is: All children Unfluoridated = 108.1, fluoridated = 108.2, The corresponding data for boys are 106.3, 104.8 and girls 109.9, 111.5 respectively. The corresponding data for Broadbent et al (2015) are for 7 u2013 13 year-olds: 99.9, 100.0 and for 38-year-olds: 98.1, 100.2. The authors may argue that comparison of the fluoridated vs unfluoridated data in their Table 1 is unwarranted because there is no correction for possible confounders. But that just reinforces the conclusion that they should have made that comparison, including the effects of confounding, and discussed it in their paper. 2: The authors base their conclusion solely on the relationships of IQ with maternal urinary fluoride or estimated fluoride intake found using linear regression. However, these relationships are extremely weak. Although the full statistical analyses are not provided the weakness is illustrated by the high degree of scattering in their Figures 3A 3B. This weakness is reinforced by the fact that Green (2018) , in her Masters thesis, reported an R-squared value of less than 5 for the relationship of boys IQ with maternal urinary F. Such low R-squared values suggest the coefficient that they place so much reliance on has little value and can usually be ignored. 3: Unusually for such studies, this paper introduces new cognitive measures, PIQ and VIQ, and one getu2019s the impression that we are asked to concentrate on PIQ rather than IQ because the effects appear larger. But there is no discussion of the value of such subtest measures and some articles suggest they should not be used for diagnosis. Ganivez (2012) for example reported that: u201cSubtest and profile interpretation methods are not consistent with Standards for Educational and Psychological Testing (AERA, APA, NCME, 1999) and should not be used in clinical decision-making until psychometric support for them is provided.u201d 4: Looking at all the relationships reported in this paper (my Figure here) we can see that only 4 of them have p-values 0.05 while 6 are not statistically significant. It is easy to cherry-pick from these results to support a pre-conceived effect of fluoridation but an objective analysis should consider all the relationships together. Also, the results from other studies like Aggeborn Ohman (2017) (which Green et al do not comment on) and Aggeborn Ohman (2021) , which found no significant relationships and Santa-Marina et al (2019) which reported positive relationships, need to be considered. When this is done l believe reliance on this paper (Green et al 2019) alone gives the wrong impression. 5: Some workers have expressed concern about the statistical analysis in this paper and it is a pity that the data is not available for an independent analysis. However, the data points provided in Figure 3 can be used and several independent workers have attempted to reproduce the reported relationships using that data. These workers have expressed concern that the figure appears not to include all the data points. For example, my own attempts at digital extraction produced only about 80% of the claimed data points for these figures. This is frustrating because while the linear regressions with these data points produce coefficients similar to those reported in the Green et al paper none of these were statistically significant for Fig 3A (although they were for Fig 3B). In particular, the p-value for the relationship of boyu2019s IQ with MUF was 0.10 and the R-squared value indicated only 1.3% of the variation was explained. While it is frustrating not to be able to repeat the statistical analysis with all the data points this apparent effect of loss of a few data points probably underlines how weak the reported relationships are. ![file] ,