with boys having a lower mean score than girls, according to a recent prospective, multicenter birth cohort study.
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“These findings were observed at fluoride levels typically found in white North American women,” wrote Rivka Green, York University, Toronto, and colleagues. “This indicates the possible need to reduce fluoride intake during pregnancy.”
This study confirms findings in a 2017 study suggesting a relationship between maternal fluoride levels and children’s later cognitive scores.
Ms. Green and colleagues evaluated 512 mother-child pairs in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort from six Canadian cities. The children were born between 2008 and 2012, underwent neurodevelopmental testing between 3 and 4 years, and were assessed using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. Full Scale IQ (FSIQ) test.
Of these, 400 mother-child pairs had data on fluoride intake, IQ, and complete covariate data; 141 of these mothers lived in areas with fluoridated tap water, while 228 mothers lived in areas without fluoridated tap water. Maternal urinary fluoride adjusted for specific gravity (MUFSG) was averaged across three trimesters of data, and the estimated fluoride level was obtained through self-reported exposure by women included in the study.
The researchers found mothers living in areas with fluoridated water had significantly higher MUFSG levels (0.69 mg/L), compared with women in areas without fluoridated water (0.40 mg/L; P equals .001). The median estimated fluoride intake was significantly higher among women living in areas with fluoridated water (0.93 mg per day) than in women who did not live in areas with fluoridated water (0.30 mg per day; P less than .001).
Overall, children scored a mean 107.16 (range, 52-143) on the IQ test, and girls had significantly higher mean IQ scores than did boys (109.56 vs. 104.61; P = .001). After adjusting for covariates of maternal age, race, parity, smoking, and alcohol status during pregnancy, child gender, gestational age, and birth weight, the researchers found a significant interaction between MUFSG and the child’s gender (P = .02), and a 1-mg/L MUFSG increase was associated with a decrease in 4.49 IQ points in boys (95% confidence interval, −8.38 to −0.60) but not girls. There also was an association between 1-mg higher daily intake of maternal fluoride intake and decreased IQ score in both boys and girls (−3.66; 95% CI, −7.16 to −0.15 ; P = .04).
Ms. Green and her colleagues acknowledged several limitations with the study, such as the short half-life of urinary fluoride and the potential inaccuracy of maternal urinary samples at predicting fetal exposure to fluoride, the self-reported nature of estimated fluoride consumption, lack of availability of maternal IQ data, and not including postnatal exposure and consumption of fluoride.
In a related editorial, David C. Bellinger, PhD, MSc, referred to a previous prospective study in Mexico City by Bashash et al. that found a maternal fluoride level of 0.9 mg/L was associated with a decrease in cognitive scores in children at 4 years and between 6 years and 12 years (Environ Health Perspect. 2017;125(9):097017. doi: 10.1289/EHP655), and noted the effect sizes seen in the Mexico City study were similar to those reported by Green et al. “If the effect sizes reported by Green et al. and others are valid, the total cognitive loss at the population level that might be associated with children’s prenatal exposure to fluoride could be substantial,” he said.
The study raises many questions, including whether there is a concentration where neurotoxicity risk is negligible, if gender plays a role (there was no gender risk difference in Bashash et al.), whether other developmental domains are affected apart from IQ, and if postnatal exposure carries a risk, Dr. Bellinger said. “The findings of Green et al. and others indicate that a dispassionate and tempered discussion of fluoride’s potential neurotoxicity is warranted, including consideration of what additional research is needed to reach more definitive conclusions about the implications, if any, for public health,” he said.
Dimitri A. Christakis, MD, MPH, editor of JAMA Pediatrics and director of the Center for Child Health, Behavior, and Development at Seattle Children’s Research Institute, said in an editor’s note that it was not an easy decision to publish the article because of the potential implications of the findings.
“The mission of the journal is to ensure that child health is optimized by bringing the best available evidence to the fore,” he said. “Publishing it serves as testament to the fact that JAMA Pediatrics is committed to disseminating the best science based entirely on the rigor of the methods and the soundness of the hypotheses tested, regardless of how contentious the results may be.”
However, “scientific inquiry is an iterative process,” Dr. Christakis said, and rarely does a single study provide “definitive evidence.
“We hope that purveyors and consumers of these findings are mindful of that as the implications of this study are debated in the public arena.”
This study was funded in a grant from the National Institute of Environmental Health Science, and the MIREC Study was funded by Chemicals Management Plan at Health Canada, the Ontario Ministry of the Environment, and the Canadian Institutes for Health Research. Dr. Bruce Lanphear reported being an unpaid expert witness for an upcoming case involving the U.S. Environmental Protection Agency and water fluoridation. Dr. Richard Hornung reported receiving personal fees from York University. Dr. E. Angeles Martinez-Mier reported receiving grants from the National Institutes of Health. The other authors report no relevant conflicts of interest. Dr. Bellinger reported no relevant conflicts of interest with regard to his editorial.
SOURCEs: Green R et al. JAMA Pediatr. 2019. doi: 10.1001/jamapediatrics.2019.1729; Bellinger. JAMA Pediatr. 2019. doi: 10.1001/ jamapediatrics.2019.1728.